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

Lilly

Status and phase: Completed; Phase 2

Conditions: Gastroesophageal Junction Adenocarcinoma; Gastric Adenocarcinoma

Treatments: Drug: Paclitaxel; Drug: Ramucirumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02514551

15541

I4T-MC-JVCZ (Other Identifier)

2014-005067-32 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 245 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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245 participants in 2 patient groups

12mg/kg Ramucirumab + 80 mg/m² Paclitaxel

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Ramucirumab

8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel

Active Comparator group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Ramucirumab