A Study of Ramucirumab (LY3009806) in Combination With Paclitaxel in Participants With Gastric Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy of an alternative dose of ramucirumab in combination with paclitaxel in participants with second-line metastatic or locally advanced, unresectable gastric or gastroesophageal junction adenocarcinoma (GEJ).

Official Title
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Randomized Phase 2 Trial Evaluating Alternative Ramucirumab Doses in Combination With Paclitaxel in Second-Line Metastatic or Locally Advanced, Unresectable Gastric or Gastroesophageal Junction Adenocarcinoma

Conditions
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Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: Ramucirumab
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant has a diagnosis of gastric or GEJ adenocarcinoma. The participant has disease progression during or within 4 months after last dose of first-line chemotherapy or during or within 6 months after the last dose of neoadjuvant or adjuvant therapy. The participant received combination chemotherapy, which must include a platinum and/or a fluoropyrimidine and must not include a taxane or antiangiogenic agent. The disease is evaluable by imaging per Response Evaluation Criteria in Solid Tumors 1.1. The participant has an Eastern Cooperative Oncology Group performance status of 0 or 1. The participant has adequate organ function: Total bilirubin ≤1.5 × the upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN. If the liver has tumor involvement, AST and ALT <5 × ULN. Serum creatinine ≤1.5 × ULN or calculated creatinine clearance ≥50 milliliters/minute. Urinary protein is <2+. Absolute neutrophil count ≥1.5 × 10^9/liter (L), platelets ≥100 × 10^9/L, and hemoglobin ≥9 grams/deciliter (5.58 millimoles/L). International normalized ratio ≤1.5 × ULN and partial thromboplastin time ≤5 seconds above ULN. The participant has an estimated life expectancy of minimum 12 weeks. The participant has resolution to Grade 1 or less by Common Terminology Criteria for Adverse Events Version 4.0, of all clinically significant toxic effects of previous therapy. The participant, if male, is sterile or agrees to use a reliable method of birth control. The participant, if female, is surgically sterile, is postmenopausal, or agrees to use a highly effective method of birth control. The participant, if female and of child-bearing potential, must have a negative pregnancy test. Exclusion Criteria: The participant is receiving therapy with any of the following: Nonsteroidal anti-inflammatory agents. Other anti-platelet agents; Aspirin use at doses up to 325 milligrams (mg)/day is permitted. The participant received radiotherapy within 14 days prior to randomization. The participant received previous chemotherapy with a cumulative dose of >900 mg per meter squared (mg/m^2) of epirubicin or >400 mg/m^2 of doxorubicin. The participant has documented brain metastases or leptomeningeal disease. The participant has a significant bleeding disorder or vasculitis. The participant experienced any arterial thromboembolic event within 6 months. The participant has symptomatic congestive heart failure or symptomatic cardiac arrhythmia. The participant has uncontrolled hypertension, despite antihypertensive intervention. The participant underwent major surgery within 28 days. The participant has a history of gastrointestinal perforation or fistula within 6 months. The participant has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention within 12 months. The participant has bowel obstruction or history of chronic diarrhea that is considered clinically significant. The participant has either of the following: Child-pugh B or C cirrhosis. The participant has a serious illness or medical condition including: Human immunodeficiency virus infection. The participant has a concurrent active malignancy other than the following: Nonmelanomatous skin cancer. In situ carcinoma of the cervix or other noninvasive carcinoma or in situ neoplasm. The participant has a serious nonhealing: (a) wound, (b) peptic ulcer, or (c) bone fracture. The participant experienced any Grade 3 or 4 venous thromboembolic event that is not adequately treated.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel<br>12 milligram per kilogram (mg/kg) ramucirumab administered intravenously (IV) on day 1 and day 15 (28 day cycles) in combination with 80 milligram per square meter (mg/m²) paclitaxel administered IV on day 1, day 8 and day 15. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Paclitaxel<br>* Administered IV<br>|
| Active Comparator: 8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel<br>8 mg/kg ramucirumab administered IV on day 1 and day 15 (28 day cycles) in combination with 80 mg/m² paclitaxel administered IV on day 1, day 8 and day 15. | Drug: Ramucirumab<br>* Administered IV<br>* Other names: Cyramza;Drug: Paclitaxel<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) in Ramucirumab 12mg/kg Arm I4T-MC-JVCZ | PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment (AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST. | Randomization to Objective Progressive Disease or Death (Up To 21 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) Ramucirumab 12mg/kg Arm and 8mg/kg Arm in I4T-MC-JVCZ | PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment(AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.Non-Target PD is unequivocal progression of existing nontarget lesions.A participant with incomplete baseline disease had PFS time censored at the enrollment date.A participant not known to have died or have RDP as of the data inclusion cutoff date for the analysis had PFS time censored at date of the last complete RDP-free disease AST. | Randomization to Objective Progressive Disease or Death (Up To 21 Months) | 
| Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination With Paclitaxel | Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination with Paclitaxel | Cycle(C) 1 Day(D) 1: Prior to Infusion(PTI),1 to 1.5 hours(hrs) after end of Infusion(EOI); C1 D15: 3 days PTI; C2 D1: 3 days PTI; C2 D15: 3 days PTI,1 to 1.5 hrs after EOI; C3 D1 and 15: 3 days PTI; C4 D1: 3 days PTI and 1 to 1.5 hrs after EOI | 
| Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) | ORR was defined as the percentage of participants who achieved a PR or CR per RECIST v.1.1.CR is the disappearance of all target lesions.Any pathological lymph nodes(whether target or non-target)must have reduction in short axis to<10mm.Tumor marker results must have normalized.PR is at least a 30% decrease in the sum of diameter of target lesions,taking as reference the baseline sum diameters.ORR is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. | Baseline to Objective Progressive Disease (Up To 21 Months) | 
| Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) [Disease Control Rate (DCR)] | DCR is defined as the percentage of participants who achieved CR, PR, or SD per RECIST v.1.1. CR is the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 mm.Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression. Non-Target PD is unequivocal progression of existing nontarget lesions. DCR=CR+PR+SD/total number of participants*100. | Baseline to Objective Progressive Disease (Up To 21 Months) | 
| Number of Participants With Anti-Ramucirumab Antibodies | Participants who had anti-ramucirumab antibodies at postbaseline. | Cycle 1 Predose through Follow-up (Up To 24 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stomach cancer