A Study to Compare Zolbetuximab (IMAB362) and Chemotherapy With Placebo and Chemotherapy in Adults With Gastric Cancer.
- Conditions
- Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or CancerLocally Advanced Unresectable Gastric Adenocarcinoma or CancerMetastatic Gastric Adenocarcinoma or CancerMetastatic Gastroesophageal Junction (GEJ) Adenocarcinoma
- Interventions
- Registration Number
- NCT03504397
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called gastroesophageal junction (GEJ) cancer. Most people with this type of cancer have a protein called Claudin 18.2 in their tumor. Zolbetuximab is thought to work by attaching to the Claudin 18.2 protein in their tumor, which switches on the body's immune system to attack the tumor. There is an unmet medical need to treat people with advanced stomach cancer or GEJ cancer. This study will give more information about how well zolbetuximab works when given with chemotherapy in adults with advanced stomach cancer or GEJ cancer. In this study, adults with advanced stomach cancer or GEJ cancer will either be given zolbetuximab with chemotherapy or a placebo with chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it. Zolbetuximab with chemotherapy has already been approved to treat gastric cancer and GEJ cancer in some countries. This study is being done in countries where zolbetuximab has not yet been approved for use. If zolbetuximab becomes approved for use in those countries taking part in this study, the study doctor will switch study treatment in those countries to the licensed zolbetuximab. If this happens, people taking part in those countries will leave this study and receive licensed zolbetuximab.
The main of the study is to check if zolbetuximab and chemotherapy can prevent or delay the worsening of people's gastric cancer and GEJ cancer compared to placebo and chemotherapy.
Adults with advanced stomach cancer or GEJ cancer can take part. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. A tumor sample of their cancer will also have the Claudin 18.2 protein. They may have been previously treated with certain standard therapies, but have not been treated with chemotherapy for their cancer. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, or have a specific heart condition, or infections.
The study treatments are either zolbetuximab with chemotherapy, or placebo with chemotherapy. People who take part will receive just 1 of the study treatments by chance. Study treatment will be double-blinded. That means that the people in the study and the study doctors will not know who takes which of the study treatments. Study treatment will be given in cycles. The study treatment is given to people slowly through a tube into a vein. This is called an infusion. People will have 4 infusions in 6-week (42-day) cycles as follows:
* Zolbetuximab or placebo - 2 infusions in a cycle.
* Chemotherapy (called modified FOLFOX6 or mFOLFOX6) - 3 infusions in a cycle. The first infusion is combined with zolbetuximab or placebo on day 1 of each cycle. People may receive zolbetuximab or placebo until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will receive mFOLFOX6 for up to 6 months (4 study treatment cycles). After the 6 months people may receive chemotherapy containing folinic acid and fluorouracil instead of mFOLFOX6. People may receive folinic acid and fluorouracil chemotherapy for more than 6 months, or until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People will visit the clinic on certain days during their study treatment. The study doctors will check if people had any medical problems from taking zolbetuximab or the other study treatments. Also, people in the study will have health checks. On some visits they will have scans to check for any changes in their cancer. People will have the option of giving a tumor sample after their study treatment has finished. People will visit the clinic after they stop their study treatment. People who start treatment with licensed zolbetuximab or mFOLFOX6 outside of this study will not need to visit the clinic. People will be asked about any medical problems and will have a health check. People will visit the clinic at 1 month after they stop their study treatment. People will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. People will have telephone health checks every 3 months. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their study treatment or not.
- Detailed Description
After the marketing approval in Japan on 26 Mar 2024, this study continued as "post marketing clinical study" in Japan. In the rest of the countries which participated in this study, this study continued as clinical study.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 565
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Female subject eligible to participate if she is not pregnant (negative serum pregnancy test at screening; female subjects with elevated serum beta human chorionic gonadotropin and a demonstrated non-pregnant status through additional testing are eligible) and at least one of the following conditions applies:
- Not a woman of child-bearing potential (WOCBP) OR
- WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs
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Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 6 months after the final study drug administration.
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Female subject must not donate ova starting at screening and throughout the study period, and for 9 months after the final administration of oxaliplatin and 6 months after the final administration of all other study drugs.
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A sexually active male subject with a female partner(s) who is of child-bearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
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Male subject must agree not to donate sperm starting at screening and throughout the study period, and for 6 months after the final study drug administration.
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Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
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Subject has histologically confirmed diagnosis of Gastric or GEJ adenocarcinoma.
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Subject has radiologically confirmed locally advanced unresectable or metastatic disease within 28 days prior to randomization.
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Subject has radiologically evaluable disease (measurable and/or non-measurable disease according to RECIST 1.1), per local assessment, ≤ 28 days prior to randomization. For subjects with only 1 evaluable lesion and prior radiotherapy ≤ 3 months before randomization, the lesion must either be outside the field of prior radiotherapy or have documented progression following radiation therapy.
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Subject's tumor expresses CLDN18.2 in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central immunohistochemistry (IHC) testing.
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Subject has a HER2-Negative tumor as determined by local or central testing on a gastric or GEJ tumor specimen. (Unique to China: Subject has a known HER2-negative gastric or GEJ tumor.)
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Subject has ECOG performance status 0 to 1.
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Subject has predicted life expectancy ≥ 12 weeks.
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Subject must meet all of the following criteria based on the centrally or locally analyzed laboratory tests collected within 14 days prior to randomization. In the case of multiple sample collections within this period, the most recent sample collection with available results should be used to determine eligibility.
- Hemoglobin (Hgb) ≥ 9 g/dL. Subjects requiring transfusions are eligible if they have a post-transfusion Hgb ≥ 9 g/dL.
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
- Platelets ≥ 100 x 10^9/L
- Albumin ≥ 2.5 g/dL
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) without liver metastases (or < 3.0 x ULN if liver metastases are present)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN without liver metastases (or ≤ 5 x ULN if liver metastases are present)
- Estimated creatinine clearance ≥ 30 mL/min
- Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
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Subject has received prior systemic chemotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. However, subject may have received either neo-adjuvant or adjuvant chemotherapy, immunotherapy or other systemic anticancer therapies, as long as it was completed at least 6 months prior to randomization. Subject may have received treatment with herbal medications that have known antitumor activity > 28 days prior to randomization.
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Subject has received radiotherapy for locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma ≤ 14 days prior to randomization and has not recovered from any related toxicity.
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Subject has received systemic immunosuppressive therapy, including systemic corticosteroids within 14 days prior to randomization. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day of prednisone), receiving a single dose of systemic corticosteroids or receiving systemic corticosteroids as premedication for radiologic imaging contrast use are allowed.
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Subject has received other investigational agents or devices within 28 days prior to randomization.
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Subject has prior severe allergic reaction or intolerance to known ingredients of zolbetuximab or other monoclonal antibodies, including humanized or chimeric antibodies.
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Subject has known immediate or delayed hypersensitivity, intolerance or contraindication to any component of study treatment.
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Subject has prior severe allergic reaction or intolerance to any component of mFOLFOX6.
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Subject has known dihydropyrimidine dehydrogenase deficiency.
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Subject has a complete gastric outlet syndrome or a partial gastric outlet syndrome with persistent/recurrent vomiting.
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Subject has significant gastric bleeding and/or untreated gastric ulcers that would exclude the subject from participation.
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Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection or known active hepatitis B (positive hepatitis B surface antigen (HBs Ag)) or C infection. NOTE: Screening for these infections should be conducted per local requirements.
- For subjects who are negative for HBs Ag, but hepatitis B core antibody (HBc Ab) positive, an HB deoxyribonucleic acid (DNA) test will be performed and if positive, the subject will be excluded.
- Subjects with positive hepatitis C virus (HCV) serology, but negative HCV ribonucleic acid (RNA) test are eligible.
- Subjects treated for HCV with undetectable viral load results are eligible.
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Subject has an active autoimmune disease that has required systemic treatment within the past 3 months prior to randomization.
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Subject has active infection requiring systemic therapy that has not completely resolved within 7 days prior to randomization.
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Subject has significant cardiovascular disease, including any of the following:
- Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, stenting, coronary artery bypass graft, cerebrovascular accident (CVA) or hypertensive crisis within 6 months prior to randomization.
- History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes)
- QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects
- History or family history of congenital long QT syndrome
- Cardiac arrhythmias requiring anti-arrhythmic medications (Subject with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible).
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Subject has a history of central nervous system metastases and/or carcinomatous meningitis from gastric/GEJ cancer.
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Subject has known peripheral sensory neuropathy > Grade 1 unless the absence of deep tendon reflexes is the sole neurological abnormality.
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Subject has had a major surgical procedure ≤ 28 days prior to randomization.
- Subject is without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
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Subject has psychiatric illness or social situations that would preclude study compliance.
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Subject has another malignancy for which treatment is required.
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Subject has any concurrent disease, infection or comorbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description mFOLFOX6 + Zolbetuximab zolbetuximab Participants received intravenous (IV) infusion (minimum 2-hour) of zolbetuximab at a loading dose of 800 milligrams per square meter (mg/m\^2) on cycle1 day1(C1D1) followed by 600 mg/m\^2 every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received upto 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4/more cycles. mFOLFOX6 was administered on Days 1, 15 \& 29 of each cycle (5-FU:400mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85mg/m\^2 IV infusion over 2 hours) A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants continued to receive 5-FU \& Folinic acid on Days 1, 15 \& 29 of each cycle at the investigator discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days. mFOLFOX6 + Zolbetuximab oxaliplatin Participants received intravenous (IV) infusion (minimum 2-hour) of zolbetuximab at a loading dose of 800 milligrams per square meter (mg/m\^2) on cycle1 day1(C1D1) followed by 600 mg/m\^2 every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received upto 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4/more cycles. mFOLFOX6 was administered on Days 1, 15 \& 29 of each cycle (5-FU:400mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85mg/m\^2 IV infusion over 2 hours) A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants continued to receive 5-FU \& Folinic acid on Days 1, 15 \& 29 of each cycle at the investigator discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days. mFOLFOX6 + Zolbetuximab folinic acid Participants received intravenous (IV) infusion (minimum 2-hour) of zolbetuximab at a loading dose of 800 milligrams per square meter (mg/m\^2) on cycle1 day1(C1D1) followed by 600 mg/m\^2 every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received upto 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4/more cycles. mFOLFOX6 was administered on Days 1, 15 \& 29 of each cycle (5-FU:400mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85mg/m\^2 IV infusion over 2 hours) A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants continued to receive 5-FU \& Folinic acid on Days 1, 15 \& 29 of each cycle at the investigator discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days. mFOLFOX6 + Zolbetuximab fluorouracil Participants received intravenous (IV) infusion (minimum 2-hour) of zolbetuximab at a loading dose of 800 milligrams per square meter (mg/m\^2) on cycle1 day1(C1D1) followed by 600 mg/m\^2 every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received upto 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4/more cycles. mFOLFOX6 was administered on Days 1, 15 \& 29 of each cycle (5-FU:400mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85mg/m\^2 IV infusion over 2 hours) A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants continued to receive 5-FU \& Folinic acid on Days 1, 15 \& 29 of each cycle at the investigator discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days. Placebo plus mFOLFOX6 placebo Participants received an IV infusion (minimum 2-hour infusion) of placebo matched to zolbetuximab on C1D1, followed by subsequent doses every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received up to 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4 or more cycles. mFOLFOX6 was administered on Days 1, 15, and 29 of each cycle (5-fluorouracil: 400 mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400 mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours). A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants could continue to receive 5-FU and folinic acid on Days 1, 15, and 29 of each cycle at the investigator's discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days. Placebo plus mFOLFOX6 oxaliplatin Participants received an IV infusion (minimum 2-hour infusion) of placebo matched to zolbetuximab on C1D1, followed by subsequent doses every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received up to 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4 or more cycles. mFOLFOX6 was administered on Days 1, 15, and 29 of each cycle (5-fluorouracil: 400 mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400 mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours). A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants could continue to receive 5-FU and folinic acid on Days 1, 15, and 29 of each cycle at the investigator's discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days. Placebo plus mFOLFOX6 folinic acid Participants received an IV infusion (minimum 2-hour infusion) of placebo matched to zolbetuximab on C1D1, followed by subsequent doses every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received up to 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4 or more cycles. mFOLFOX6 was administered on Days 1, 15, and 29 of each cycle (5-fluorouracil: 400 mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400 mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours). A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants could continue to receive 5-FU and folinic acid on Days 1, 15, and 29 of each cycle at the investigator's discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days. Placebo plus mFOLFOX6 fluorouracil Participants received an IV infusion (minimum 2-hour infusion) of placebo matched to zolbetuximab on C1D1, followed by subsequent doses every 3 weeks starting from C1D22 until study treatment discontinuation criteria were met. Participants also received up to 12 treatments of mFOLFOX6 (or components if some were discontinued due to toxicity) over 4 or more cycles. mFOLFOX6 was administered on Days 1, 15, and 29 of each cycle (5-fluorouracil: 400 mg/m\^2 IV bolus over 5-15 minutes followed by 2400mg/m\^2 over 46-48 hours continuous IV infusion every 2 weeks for 4 cycles. Folinic acid: 400 mg/m\^2 IV infusion over 2 hours; oxaliplatin: 85 mg/m\^2 IV infusion over 2 hours). A maximum of 12 doses of oxaliplatin was permitted. After mFOLFOX6 treatments, participants could continue to receive 5-FU and folinic acid on Days 1, 15, and 29 of each cycle at the investigator's discretion or until study treatment discontinuation criteria were met. Each cycle was approximately 42 days.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) From date of randomization until the date of first documented radiological progression or date of death from any cause, whichever occurred first (up to 50 months and 19 days) PFS was defined as the time from the date of randomization until the date of radiological progressive disease (PD) (per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 by independent review committee \[IRC\]) or death from any cause, whichever was earliest. PD was defined as development of new, or progression of existing metastases to the primary cancer under the study. Kaplan -Meier (KM) estimates was used.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From the date of randomization until 63 months OS was defined as the time from the date of randomization until the date of death from any cause. Kaplan-Meier estimates was used.
Time to Confirmed Deterioration (TTCD) Using Physical Functioning (PF) as Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30) From the date of randomization until 51 months TTCD: time from randomization to first clinically meaning full deterioration (CMD) that was confirmed at next scheduled visit. EORTC-QLQ-C30 was a 30-item cancer-specific instrument consisting of 5 functional scales (physical,role,emotional,social \& cognitive), 9 symptom scales (fatigue, nausea/vomiting,general pain,dyspnea,insomnia,appetite loss,constipation,diarrhea,financial difficulties) \& global health status scale. Most items were scored 1(not at all) to 4(very much) except for items contributing to global health status/QoL, which were scored 1(very poor) to 7(excellent). All raw domain scores were linearly transformed to 0-100scale with higher scores on symptoms indicate worse health state. CMD was defined if a participant's change from baseline exceeded a pre-specified threshold of -13. This was derived from an Exit Survey conducted using Patient Global Impression of Severity/Change(PGIS/PGIC) questionnaires as an anchor for estimating meaningful change. KM estimates was used.
Time to Confirmed Deterioration (TTCD) Using Oesophago-gastric Questionnaire (OG25) on Abdominal Pain and Discomfort as Measured by EORTC QLQ-OG25 From the date of randomization until 51 months TTCD: time from randomization to first CMD that was confirmed at next scheduled visit. EORTC QLQ-OG25 evaluated gastric and GEJ cancer specific symptoms. A 25item instrument with 6 scales: dysphagia (3 items),eating restrictions(4 ),reflux(2),odynophagia(2),pain and discomfort(2), anxiety(2),as well as 10 single items: eating in front of others, dry mouth, trouble with taste, body image, trouble swallowing saliva, choked when swallowing, trouble with coughing, trouble talking, weight and hair loss. Items were scored:1: not at all; 2: a little, 3: quite a bit, 4: very much, and were transformed linearly into scores (0 to 100) with higher scores indicating worse symptoms. CMD was defined if a participant's change from baseline exceeded a pre-specified threshold of 16.67. This was derived from an Exit Survey conducted to use PGIS/PGIC questionnaires as an anchor for estimating the meaningful change. KM estimates was used.
Time to Confirmed Deterioration (TTCD) Using Global Health Status as Measured by EORTC QLQ-C30 From the date of randomization until 51 months TTCD: time from randomization to first CMD that was confirmed at the next scheduled visit. The EORTC-QLQ-C30 was a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Most items were scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which were scored 1 ("very poor") to 7 ("excellent"). All raw domain scores were linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state. CMD was defined if a participant's change from baseline exceeded a pre-specified threshold of -10. This was derived from an Exit Survey conducted to use PGIS/PGIC questionnaires as an anchor for estimating the meaningful change. KM estimates was used.
Objective Response Rate (ORR) From the date of randomization until 51 months ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as was assessed by IRC per RECIST 1.1. CR was defined as complete resolution of all attributable clinical symptoms and physical findings. PR was defined as partial resolution of at Least some of the clinical symptoms and physical findings.
Duration Of Response (DOR) From date of first response (CR/PR) until 51 months DOR was defined as the time from the date of the first response (CR/PR) until the date of PD as assessed by IRC per RECIST 1.1 or date of death from any cause, whichever is earliest.CR was defined as complete resolution of all attributable clinical symptoms and physical findings. PR was defined as partial resolution of at Least some of the clinical symptoms and physical findings.PD was defined as development of new, or progression of existing metastases to the primary cancer under the sudy.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) From first dose until 51 months An Adverse event (AE) is any untoward medical occurrence in a participant administered a study drug, and which does not have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or notconsidered related to the medicinal product. TEAE defined as an AE observed after starting administration of the study drug through 30 days after the last dose.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Baseline, cycle (C) 1 day (D) 22, D1 and D22 of C2 through C30, C31D1, C32D1 ECOG grades 0-5, where 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair and 5 = Dead.
Change From Baseline in Health Related Quality of Life (HRQoL) Measured by the EORTC-QLQ-C30 Questionnaire Baseline, C1D22, D1 and D22 of C2 through C19, C20D1, C21D1, 30 day follow up, 90 day follow up The EORTC-QLQ-C30 is a 30-item cancer-specific instrument consisting of 5 functional scales (physical, role, emotional, social and cognitive), 9 symptom scales/items (fatigue, nausea/vomiting, general pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status scale. Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state.
Change From Baseline in HRQoL Measured by the QLQ-OG25 Questionnaire Baseline, C1D22, D1 and D22 of C2 through C19, C20D1, C21D1, 30 day follow up, 90 day follow up The EORTC-QLQ-OG25 consists of a 25-item instrument that evaluates gastric and GEJ cancer-specific symptoms such as stomach discomfort, difficulties eating and swallowing and indigestion. This module consists of 6 scales: dysphagia (3 items), eating restrictions (4 items), reflux (2 items), odynophagia (2 items), pain and discomfort (2 items) and anxiety (2 items), as well as 10 single items: eating in front of others, dry mouth, trouble with taste, body image, trouble swallowing saliva, choked when swallowing, trouble with coughing, trouble talking, weight loss and hair loss. All questions have four response alternatives (1:not at all; 2:a little, 3:quite a bit, 4:very much). Questionnaire responses were transformed lineraly into scores ranging from 0 to 100 For symptom scales/items, higher scores indicate worse symptoms.
Change From Baseline in HRQoL Measured by Global Pain (GP) Baseline, C1D22, D1 and D22 of C2 through C19, C20D1, C21D1, 30 day follow up, 90 day follow up The GP instrument is a single assessment of overall pain. Participants were assessed in global pain according to the following response categories: 1= no pain (anymore), 2 = less pain, 3 = no change and 4 = more pain.
Change From Baseline in HRQoL Measured by the EuroQOL Five Dimensions Questionnaire 5L (EQ-5D-5L) Questionnaire Baseline, C1D22, D1 and D22 of C2 through C19, C20D1, C21D1, 30 day follow up, 90 day follow up EQ-5D-5L is a standardized instrument for use as a measure of health outcomes consisting of 6 items that cover 5 main domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a general visual analog scale for health status.It was developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale. Responses to the 5 items will also be converted to a weighted health state index (utility score) based on values derived from general population samples.
Pharmacokinetics (PK) of Zolbetuximab in Serum: Trough Concentration (Ctrough) Predose on C1D22, C3D1, C5D1, C7D1, C9D1 Ctrough was defined as the predose concentration at the end of dosing interval.
Number of Participants With Anti-drug Antibodies (ADA) Predose on C1D1, C1D22, C3D1, C5D1, C7D1, C9D1, 30-day follow up, 90-day follow up Immunogenicity will be measured by the number of participants that are ADA positive.
Trial Locations
- Locations (214)
St. Jude Hospital Yorba Linda
🇺🇸Fullerton, California, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Miami
🇺🇸Miami, Florida, United States
Site CN86001
🇨🇳Xiamen, China
University of California - San Francisco
🇺🇸San Francisco, California, United States
Site BR55010
🇧🇷Brasília, Distrito Federal, Brazil
Site TW88605
🇨🇳Kwei-Shan, Taoyuan, Taiwan
Site BR55006
🇧🇷Lajeado, Rio Grande Do Sul, Brazil
University of Oklahoma Health Science Center
🇺🇸Oklahoma City, Oklahoma, United States
Site FR33011
🇫🇷Montpellier Cedex 5, Languedoc-Roussillon, France
University of Arizona
🇺🇸Phoenix, Arizona, United States
CBCC Global Research, Inc. at Comprehensive Blood and Cancer
🇺🇸Bakersfield, California, United States
Loma Linda University
🇺🇸Loma Linda, California, United States
The Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
Pacific Shores Medical Group
🇺🇸Huntington Beach, California, United States
Northwestern University Medical Center
🇺🇸Chicago, Illinois, United States
University of Maryland Medical Center(UMMC)Transplant Center
🇺🇸Baltimore, Maryland, United States
Maryland Oncology Hematology
🇺🇸Brandywine, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
The Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Earle A. Chiles Research Institute
🇺🇸Portland, Oregon, United States
Sanford Cancer Center
🇺🇸Sioux Falls, South Dakota, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Site AU61002
🇦🇺Douglas, Queensland, Australia
Site BE32007
🇧🇪Edegem, Antwerpen, Belgium
Site BE32001
🇧🇪Bruxelles, Bruxelles-Capitale, Région De, Belgium
Site BE32002
🇧🇪Bruxelles, Liege, Belgium
Site BE32012
🇧🇪Gent, Oost-Vlaanderen, Belgium
Site BE32010
🇧🇪Haine-Saint-Paul, Belgium
Site BE32005
🇧🇪Brugge, Belgium
Site BR55017
🇧🇷Belo Horizonte, Brazil
Site BR55016
🇧🇷Passo Fundo, Brazil
Site BR55018
🇧🇷Santa Catarina, Brazil
Site BR55009
🇧🇷São Paulo, Brazil
Site BR55004
🇧🇷São Paulo, Brazil
Site DE49011
🇩🇪Berlin, Germany
Site CA15005
🇨🇦Edmonton, Alberta, Canada
Site IT39008
🇮🇹Milano, Italy
Site CA15011
🇨🇦Toronto, Ontario, Canada
Site CA15002
🇨🇦Montreal, Quebec, Canada
Site CA15008
🇨🇦Montreal, Quebec, Canada
Site CL56008
🇨🇱Providencia, Chile
Site CL56005
🇨🇱Santiago, Chile
Site CN86006
🇨🇳Nanjing, Jiangsu, China
Site CN86009
🇨🇳Beijing, China
Site CN86004
🇨🇳Hangzhou Shi, Zhejiang, China
Site CN86005
🇨🇳Hefei, China
Site CN86002
🇨🇳Beijing, China
Site CN86008
🇨🇳Zhengzhou, China
Site FR33008
🇫🇷Besancon cedex, Franche-Comte, France
Site DE49019
🇩🇪Heilbronn, Germany
Site FR33103
🇫🇷Creteil, France
Site FR33003
🇫🇷Lyon, Rhone, France
Site FR33104
🇫🇷Saint Priest en Jarez, France
Site DE49007
🇩🇪Munchen, Bayern, Germany
Site DE49021
🇩🇪Halle, Sachsen-Anhalt, Germany
Site DE49002
🇩🇪Mainz, Rheinland-Pfalz, Germany
Site DE49012
🇩🇪Berlin, Germany
Site DE49015
🇩🇪Magdeburg, Sachsen-Anhalt, Germany
Site DE49004
🇩🇪Leipzig, Sachsen, Germany
Site DE49010
🇩🇪Dresden, Sachsen, Germany
Site IL97210
🇮🇱HaDarom, Israel
Site IL97206
🇮🇱Kfar Saba, HaMerkaz, Israel
Site IT39011
🇮🇹Meldola, Forli, Italy
Site IL97203
🇮🇱Tel Aviv, Israel
Site IL97202
🇮🇱Jerusalem, Israel
Site IT39023
🇮🇹Vicenza, VI, Italy
Site IT39020
🇮🇹Monza, Lombardia, Italy
Site IT39013
🇮🇹Ancona, Italy
Site IT39004
🇮🇹Bergamo, Italy
Site IT39009
🇮🇹Cremona, Italy
Site IT39021
🇮🇹Modena, Italy
Site IT39016
🇮🇹Padova, Italy
Site IT39018
🇮🇹Perugia, Italy
Site IT39019
🇮🇹Pisa, Italy
Site IT39015
🇮🇹Roma, Italy
Site IT39024
🇮🇹Turin TO, Italy
Site JP81003
🇯🇵Kashiwa, Chiba, Japan
Site JP81014
🇯🇵Kobe, Hyogo, Japan
Site JP81001
🇯🇵Suita, Osaka, Japan
Site JP81015
🇯🇵Hidaka, Saitama, Japan
Site JP81012
🇯🇵Sunto-gun, Shizuoka, Japan
Site JP81010
🇯🇵Kitaadachi-gun, Saitama, Japan
Site JP81008
🇯🇵Koto-ku, Tokyo, Japan
Site JP81005
🇯🇵Fukuoka, Japan
Site JP81004
🇯🇵Osaka, Japan
Site KR82003
🇰🇷Seoul, Korea, Republic of
Site KR82008
🇰🇷Incheon, Korea, Republic of
Site KR82006
🇰🇷Seoul, Korea, Republic of
Site MX52007
🇲🇽Ciudad de México, Distrito Federal, Mexico
Site MX52001
🇲🇽Aguascalientes, Mexico
Site MX52004
🇲🇽Oaxaca, Mexico
Site PE51003
🇵🇪Arequipa, Peru
Site PE51005
🇵🇪Lima, Peru
Site PE51001
🇵🇪Lima, Peru
Site PL48009
🇵🇱Warszawa, Poland
Site PL48002
🇵🇱Brzozow, Podkarpackie, Poland
Site ES34016
🇪🇸Barcelona, Spain
Site ES34019
🇪🇸Burgos, Spain
Site ES34015
🇪🇸Barcelona, Spain
Site ES34003
🇪🇸Murcia, Spain
Site ES34008
🇪🇸Madrid, Spain
Site ES34017
🇪🇸Madrid, Spain
Site TW88608
🇨🇳Kaohsiung, Taiwan
Site TW88603
🇨🇳Taichung, Taiwan
Site GB44101
🇬🇧London, London, City Of, United Kingdom
Site GB44102
🇬🇧Sutton, Surrey, United Kingdom
Site GB44103
🇬🇧Cambridge, United Kingdom
Site GB44004
🇬🇧London, United Kingdom
Site GB44002
🇬🇧London, United Kingdom
Site GB44008
🇬🇧Leeds, United Kingdom
Site GB44001
🇬🇧Manchester, United Kingdom
Site ES34011
🇪🇸Alcorcon, Madrid, Spain
Site ES34004
🇪🇸Madrid, Spain
Site KR82005
🇰🇷Seoul, Korea, Republic of
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Health Partners Institute
🇺🇸Saint Louis Park, Minnesota, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
MultiCare Regional Cancer Center - Gig Harbor
🇺🇸Auburn, Washington, United States
Site AU61007
🇦🇺Kogarah, Australia
Inova Dwight and Martha Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Memorial Sloan Kettering Cancer Center
🇺🇸Uniondale, New York, United States
City of Hope Nat'l Medical Center
🇺🇸Duarte, California, United States
The University of Arizona Medical Center
🇺🇸Tucson, Arizona, United States
Memorial Cancer Institute - West
🇺🇸Hollywood, Florida, United States
Memorial Hospital West
🇺🇸Pembroke Pines, Florida, United States
Cancer Treatment Centers of America, Atlanta
🇺🇸Newnan, Georgia, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Lancaster General Hospital
🇺🇸Lancaster, Pennsylvania, United States
Cancer Treatment Centers of America, Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Rhode Island Hospital-Lifespan Cancer Institute
🇺🇸Providence, Rhode Island, United States
Site AU61011
🇦🇺Tugun, Queensland, Australia
Site AU61008
🇦🇺Adelaide, South Australia, Australia
Site AU61006
🇦🇺East Bentleigh, Victoria, Australia
Site BE32004
🇧🇪Brussels, Belgium
Site BE32006
🇧🇪Leuven, Vlaams Brabant, Belgium
Site BE32011
🇧🇪Charleroi, Belgium
Site BR55002
🇧🇷Itajai, Santa Catarina, Brazil
Site BR55003
🇧🇷Santo Andre, Sao Paulo, Brazil
Site BR55005
🇧🇷Sao Jose do Rio Preto, Sao Paulo, Brazil
Site BR55015
🇧🇷Rio de Janeiro, Brazil
Site CA15009
🇨🇦Saint-John, New Brunswick, Canada
Site CL56007
🇨🇱Valdivia, Chile
Site CN86003
🇨🇳Haerbin, Heilongjiang, China
Site CO57009
🇨🇴Bogota, DC, Colombia
Site CO57005
🇨🇴Cali, Valle, Colombia
Site CO57002
🇨🇴Medellin, Colombia
Site FR33001
🇫🇷Rennes, Bretagne, France
Site FR33009
🇫🇷Dijon, Bourgogne, France
Site FR33010
🇫🇷Brest Cedex, Bretagne, France
Site FR33005
🇫🇷Nice, Provence-Alpes-Côte-d'Azur, France
Site FR33002
🇫🇷Paris cedex, Paris, France
Site FR33101
🇫🇷St Herblain, Pays-de-la-Loire, France
Site FR33007
🇫🇷Nice Cedex 2, France
Site FR33006
🇫🇷Poitiers, Vienne, France
Site DE49018
🇩🇪Dresden, Germany
Site IL97201
🇮🇱Haifa, Israel
Site IL97209
🇮🇱Holon, Israel
Site IT39006
🇮🇹Milano, Italy
Site IT39012
🇮🇹Parma, Italy
Site IT39003
🇮🇹Piacenza, Italy
Site IT39022
🇮🇹Reggio Emilia, Italy
Site IT39026
🇮🇹Terni, Italy
Site JP81002
🇯🇵Matsuyama, Ehime, Japan
Site JP81009
🇯🇵Nagoya, Aichi, Japan
Site JP81007
🇯🇵Sapporo, Hokkaido, Japan
Site JP81013
🇯🇵Bunkyo-ku, Tokyo, Japan
Site JP81011
🇯🇵Osaka, Japan
Site KR82002
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Site KR82009
🇰🇷Suwon-si, Gyeonggido [Kyonggi-do], Korea, Republic of
Site KR82004
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Site KR82007
🇰🇷Seoul, Korea, Republic of
Site MX52010
🇲🇽Veracruz, Ver, Veracruz, Mexico
Site MX52003
🇲🇽Distrito Federal, Mexico
Site PL48004
🇵🇱Lublin, Lubuskie, Poland
Site PL48005
🇵🇱Wieliszew, Mazowieckie, Poland
Site ES34010
🇪🇸Avila, Castilla Y Leon, Spain
Site ES34013
🇪🇸Badalona, Barcelona, Spain
Site ES34005
🇪🇸Barcelona, Spain
Site ES34018
🇪🇸Sevilla, Spain
Site ES34006
🇪🇸Zaragoza, Spain
Site TW88604
🇨🇳Kaohsiung, Taiwan
Site TW88607
🇨🇳Tainan, Taiwan
Site TW88606
🇨🇳Taipei, Taiwan
Site TW88601
🇨🇳Taipei, Taiwan
Site GB44003
🇬🇧Aberdeen, Aberdeenshire, United Kingdom
Site GB44009
🇬🇧Coventry, United Kingdom
Site GB44104
🇬🇧Dundee, United Kingdom
University of California Davis
🇺🇸Sacramento, California, United States
Orlando Health Inc
🇺🇸Orlando, Florida, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Site CL56003
🇨🇱Providencia, Santiago, Chile
Site DE49008
🇩🇪Munich, Bavaria, Germany
Site MX52008
🇲🇽San Luis De Potosi, Mexico
Site CO57006
🇨🇴Medellín, Antioquia, Colombia
Site PL48007
🇵🇱Ostroleka, Mazowieckie, Poland
Site PE51006
🇵🇪Lima, Peru
Site PE51004
🇵🇪San Isidro, Lima, Peru
Site CO57007
🇨🇴Monteria, Córdoba, Colombia
Site MX52002
🇲🇽Mexico, Distrito Federal, Mexico
Site BE32008
🇧🇪Mons, Hainaut, Belgium
Site CO57001
🇨🇴Cali, Colombia
Site JP81006
🇯🇵Chuo-ku, Tokyo, Japan
Site MX52009
🇲🇽Jalisco, Mexico
Site BR55007
🇧🇷Barretos, São Paulo, Brazil
Precision Cancer Research -Dayton Physicians Network
🇺🇸Middletown, Ohio, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States