Clinical Trial Testing the efficacy and Safety of Two Ramucirumab Doses Given as Second Line Treatment to Patients with Stomach Cancer
- Conditions
- Second-Line Metastatic or Locally Advanced, Unresectable Gastric or Gastroesophageal Junction AdenocarcinomaMedDRA version: 18.1 Level: PT Classification code 10063916 Term: Metastatic gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-005067-32-BE
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 240
[1] The patient has a histopathologically or cytologically confirmed diagnosis of gastric or GEJ (Siewert Types I-III) adenocarcinoma.
[2] The patient has documented disease progression during or within 4 months after the last dose of first-line chemotherapy for metastatic disease, or during or within 6 months after the last dose of neoadjuvant or adjuvant therapy.
[3] The patient received combination chemotherapy prior to disease progression.
Prior chemotherapy regimens must include a platinum and/or a fluoropyrimidine component and must not include a taxane or antiangiogenic agent (either approved or experimental treatment).
[4] The patient has metastatic disease or locally advanced disease that is evaluable, by radiological imaging per RECIST 1.1.
[5] The patient has an ECOG performance status of 0 or 1.
[6] The patient has adequate organ function, including:
a. Total bilirubin equal to or less than 1.5 × the upper limit of institutional normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal 3 × ULN. If the liver has tumor involvement, AST and ALT <5 × ULN are acceptable.
b. Serum creatinine less or equl 1.5 × ULN or calculated creatinine clearance (per the Cockcroft-Gault formula or equivalent and/or 24-hour urine collection) minimum 50 mL/min
c. Urinary protein is <2+ on dipstick or routine urinalysis.
d. Absolute neutrophil count minimum 1.5 × 10e9/L, platelets minimum 100 × 10e9/L, and hemoglobin minimum 9 g/dL (5.58 mmol/L). Packed red blood cell transfusions are not allowed within 1 week prior to baseline hematology profile.
e. International normalized ratio (INR) less or equal 1.5 × ULN and partial thromboplastin time less or equal 5 seconds above ULN, unless the
patient is receiving anticoagulation therapy. Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable
coagulation profile prior to randomization.
[7] The patient is at least 18 years old (or of an acceptable age according to local regulations, whichever is older).
[8] The patient has provided written informed consent prior to any study-specific procedures and is amenable to compliance with protocol schedules and testing.
[9] The patient has an estimated life expectancy of minumum 12 weeks in the judgement of the investigator.
[10] The patient has resolution to Grade 1 or less by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (NCI 2009), of all clinically significant toxic effects of previous anticancer therapy.
[11] The patient, if male, is sterile (including vasectomy confirmed by post-vasectomy semen analysis) or agrees to use a reliable method of birth
control and to not donate sperm during the study and for at least 12 weeks following the last dose of study treatment.
[12] The patient, if female, is surgically sterile, is postmenopausal, or agrees to use a highly effective method of birth control during the
[1] The patient has cancer with histology other than adenocarcinoma.
[2] The patient is receiving chronic therapy with any of the following within 7 days prior to randomization:
a. nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents)
b. other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide); Aspirin use at doses up to 325 mg/day is permitted.
[3] The patient received radiotherapy within 14 days prior to randomization.
Palliative radiotherapy during the study, if clinically indicated, can be considered after consultation with the Lilly clinical research physician (CRP). Any lesion requiring palliative radiotherapy or which has been previously irradiated cannot be considered for response assessment.
[4] The patient received >1 line of prior therapy for the treatment of locally advanced and unresectable or metastatic gastric or GEJ (Siewert Types I-III) adenocarcinoma.
[5] The patient received previous systemic chemotherapy with a cumulative dose of >900 mg/m2 of epirubicin or >400 mg/m2 of doxorubicin.
[6] The patient received previous treatment with agents targeting the VEGF/VEGF Receptor 2 signaling pathway, including previous exposure to
ramucirumab.
[7] The patient has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression. Screening of asymptomatic patients is not required.
[8] The patient has a significant bleeding disorder or vasculitis or had a Grade 3 or more bleeding episode within 12 weeks prior to randomization.
[9] The patient experienced any arterial thromboembolic event (ATE), including
myocardial infarction, unstable angina, cerebrovascular accident , or transient ischemic attack, within 6 months prior to randomization.
[10] The patient has symptomatic congestive heart failure (CHF; New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
[11] The patient has uncontrolled hypertension, as defined in CTCAE Version 4.0, prior to initiating study treatment, despite antihypertensive intervention.
[12] The patient underwent major surgery within 28 days prior to randomization or central venous access device placement within 7 days prior to randomization.
[13] The patient plans to undergo elective major surgery during the course of the trial.
[14] The patient has a history of gastrointestinal (GI) perforation or fistula within 6 months prior to randomization.
[15] The patient has a history of inflammatory bowel disease or Crohn’s disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) within 12 months prior to randomization.
[16] The patient has an acute or subacute bowel obstruction or history of chronic diarrhea that is considered clinically significant in the opinion of the
investigator.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: Evaluate the efficacy of ramucirumab 12 mg/kg versus placebo, both in<br> combination with paclitaxel, in terms of PFS<br> ;<br> Secondary Objective: Evaluate the efficacy of ramucirumab 12 mg/kg versus 8 mg/kg, both in<br> combination with paclitaxel, in terms of PFS<br> <br> PK of ramucirumab in combination with paclitaxel<br> <br> ORR, DRC, Immunogenicity<br> ;<br> Primary end point(s): efficacy: PFS, as determined by investigator assessment per<br> RECIST 1.1, (12 mg/kg versus placebo)<br> ;Timepoint(s) of evaluation of this end point: The final analysis of the primary endpoints will occur after 191 randomized patients have completed (Progression Free Survival Event) or discontinued for any reason prior to completing.
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): efficacy: PFS, as determined by investigator assessment per<br> RECIST 1.1, (12 mg/kg versus ramucirumab 8 mg/kg)<br> <br> Minimum ramucirumab concentration in serum<br> <br> The safety endpoints evaluated will include but are not limited to<br> the following:<br> - TEAEs, AESIs, SAEs, and hospitalizations<br> - Clinical laboratory tests, vital signs, and physical examinations<br> - ORR, DCR<br> - Blood samples for immunogenicity testing will be collected to<br> determine antibody production against ramucirumab<br> ;Timepoint(s) of evaluation of this end point: The final analysis of the secondary endpoints will occur after 191 randomized patients have completed (Progression Free Survival Event) or discontinued for any reason prior to completing.