Study investigating new drug, IMC-1121B, in patients with cancer of the stomach spreading to other parts of the body - cancer does not respond to or continues to grow after standard chemotherapy (a combination of medicines including platinum or fluoropyrimidine drugs). Patients assigned to 1 of 2 groups: one group will receive IMC-1121B, the other group an inactive substance (placebo). Neither patient nor doctor will know the treatment group. All patients will be treated with paclitaxel.
- Conditions
- Metastatic gastric or gastroesophageal adenocarcinomaMedDRA version: 18.1Level: PTClassification code 10063916Term: Metastatic gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2010-020426-18-HU
- Lead Sponsor
- ImClone LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 663
1. The patient has provided signed informed consent and is amenable to compliance with protocol schedules and testing.
2. The patient is at least 18 years of age (or of an acceptable age according to local regulations, whichever is older).
3. The patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study entry.
4. The patient has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma.
5. The patient has metastatic disease or locally advanced, unresectable disease.
6. The patient has experienced documented objective radiographic or clinical disease progression (eg, any new or worsening malignant effusion documented by ultrasound examination) which may be confirmed by pathologic criteria (histology and/or cytology) if appropriate, during first-line therapy, or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin) for unresectable or metastatic disease.
7. The patient has resolution to Grade = 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.02, of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer therapy.
8. The patient has adequate organ function, defined as:
• Total bilirubin = 1.5 times upper limit of normal value (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) = 3 x ULN for ALAT/ASAT if no liver metastases, < 5 x ULN if liver metastases;
• Serum creatinine = 1.5 ULN or calculated creatinine clearance (per the Cockcroft-Gault formula or equivalent
and/or 24-hour urine collection) = 50 ml/min;
• Absolute neutrophil count (ANC) = 1.5 x 10^9/L, hemoglobin = 9 g/dL (5.58 mmol/L; packed red blood cell
transfusions are not permitted within one week prior to baseline hematology profile), and platelets = 100 x 10^9/L; and
• International Normalized Ratio (INR) = 1.5 or Prothrombin time (PT) = 1.5 x ULN
• Partial thromboplastin time (PTT/aPTT) = 1.5 x ULN.
9. The patient’s urinary protein is = 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates proteinuria = 2+, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study.
10. The patient, if female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method (failure rate < 1%) during and for 12 weeks after the treatment period (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method). If male, the patient is surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period. The label (e.g. SmPC, USPI etc) requirements with regard to the methods and duration of contraception during and after treatment with paclitaxel can differ between countries. Country specific
requirements will apply only if they are more stringent than those already stipulated in the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 442
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 221
1. The patient has squamous cell or undifferentiated gastric cancer.
2. The patient has undergone major surgery within 28 days prior to randomization, or central venous access device placement within 7 days prior to randomization.
3. The patient has received any chemotherapy other than platinum and fluoropyrimidine with or without anthracycline for advanced gastric or GEJ adenocarcinoma.
4. The patient has received previous systemic chemotherapy with a cumulative dose of > 900 mg/m2 of epirubicin or > 400 mg/m2 of doxorubicin.
5. The patient has received any previous systemic therapy (including investigational agents) targeting VEGF or the VEGFR signaling pathways. Other previous targeted therapies are permitted, if stopped at least 28 days prior to randomization.
6. The patient has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered significant”) during the 3 months prior to randomization.
7. The patient is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents. Patients receiving prophylactic, low-dose anticoagulation therapy are eligible provided that the coagulation parameters defined in the inclusion criteria (INR = 1.5 and = 1.5 x ULN) or (PT = 1.5 ULN and PTT/aPTT = 1.5 x ULN) are met.
8. The patient is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs, e.g., indomethacin, ibuprofen, naproxen or similar agents) or other anti-platelet agents (e.g., clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin use at doses up to 325mg/day is permitted.
9. The patient has significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 3 months prior to study entry.
10. History of gastrointestinal perforation and/or fistulae within 6 months prior to randomization.
11. The patient has symptomatic congestive heart failure (New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
12. The patient has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
13. The patient has uncontrolled arterial hypertension = 150 / = 90 mm Hg despite standard medical management.
14. The patient has a serious or non healing wound or peptic ulcer or bone fracture within 28 days prior to randomization.
15. The patient has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
16. The patient has a serious illness or medical condition(s) including, but not limited to the following:
• Known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
• Active or uncontrolled clinically serious infection
• Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to the
study
• Uncontrolled metabolic disorders or other nonmalignant organ or systemic diseases or secondary effects of cancer that induce a high medical risk and/or make assessment of survival uncertain
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method