A Phase 2 Study of Ramucirumab (LY3009806) in Participants With Gastric or Gastroesophageal Junction (GEJ) Cancer

Lilly

Status and phase

Completed

Phase 2

Conditions

Gastroesophageal Junction Adenocarcinoma

Gastric Adenocarcinoma

Treatments

Drug: Ramucirumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT02443883

15608

I4T-MC-JVDB (Other Identifier)

2014-003791-23 (EudraCT Number)

Details and patient eligibility

About

The main purpose of this study was to evaluate the safety and pharmacokinetics of administering various dose regimens of ramucirumab in participants with advanced gastric cancer whose disease has progressed during or following prior chemotherapy.

Enrollment

164 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

The participant has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ).
The participant 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.
The participant 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.
The participant has metastatic disease or locally advanced disease that is measurable or nonmeasurable, but is evaluable disease by radiological imaging per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).
Patients are eligible if they are considered not appropriate, for whatever reason, for treatment with ramucirumab in combination with paclitaxel.
The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
The participant has adequate organ function, including:
- Total bilirubin 1.5 × the upper limit of institutional normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 × ULN. If the liver has tumor involvement, AST and ALT <5 × ULN are acceptable.
- Serum creatinine 1.5 × ULN or calculated creatinine clearance (per the Cockcroft-Gault formula or equivalent and/or 24-hour urine collection) 60 milliliters/minute (mL/min).
- Urinary protein is <2+ on dipstick or routine urinalysis.
- Absolute neutrophil count 1.5 × 10^9/Liter (L), platelets 100 × 10^9/L, and hemoglobin 9 g/deciliter (dL) (5.58 millimoles/Liter).
- International normalized ratio 1.5 × ULN or prothrombin time 5 seconds above ULN.
- Partial thromboplastin time 5 seconds above ULN.
The participant has an estimated life expectancy of 12 weeks in the judgment of the investigator.
The participant, if female and of child-bearing potential, must have a negative serum or urine pregnancy test within 7 days prior to randomization.

Exclusion criteria

The participant has squamous cell or undifferentiated gastric cancer.
The participant is receiving chronic therapy with any of the following within 7 days prior to randomization:
- Nonsteroidal anti-inflammatory agents (NSAIDs; such as indomethacin, ibuprofen, naproxen, or similar agents), or
- Other anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or anagrelide). 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 >1 line of prior therapy for the treatment of locally advanced and unresectable or metastatic gastric or GEJ (Siewert Types I-III) adenocarcinoma.
The participant received previous treatment with agents targeting the vascular endothelial growth factor (VEGF)/VEGF receptor 2 signaling pathway.
The participant has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
The participant experienced any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization.
The participant has symptomatic congestive heart failure (New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
The participant has uncontrolled hypertension, as defined in Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0, prior to initiating study treatment, despite antihypertensive intervention.
The participant underwent major surgery within 28 days prior to randomization or central venous access device placement within 7 days prior to randomization.
The participant has a history of gastrointestinal perforation or fistula within 6 months prior to randomization.
The participant has any condition (for example, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggests that the participant is, in the investigator's opinion, not an appropriate candidate for the study.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

164 participants in 4 patient groups

Ramucirumab Regimen 1

Experimental group

Description:

Standard dose of 8 milligram per kilogram (mg/kg) ramucirumab given intravenously (IV) on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met.

Treatment:

Drug: Ramucirumab

Ramucirumab Regimen 2

Experimental group

Description:

Experimental dose of 12 mg/kg ramucirumab given IV on day 1 and day 15 of each cycle (28-day cycle) until discontinuation criteria are met.

Treatment:

Drug: Ramucirumab

Ramucirumab Regimen 3

Experimental group

Description:

Experimental dose of 6 mg/kg ramucirumab given IV on day 1, 8, 15 and 22 of each cycle (28-day cycle) until discontinuation criteria are met.