Study of IMC-1121B (Ramucirumab) With Best Supportive Care in Participants With Gastric Cancer and Adenocarcinoma

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00917384
• Date of registration: 08/06/2009
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: Study of IMC-1121B (Ramucirumab) With Best Supportive Care in Participants With Gastric Cancer and Adenocarcinoma
• Scientific title: A Phase 3, Randomized, Double-Blinded Study of IMC-1121B and Best Supportive Care (BSC) Versus Placebo and BSC in the Treatment of Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Following Disease Progression on First-Line Platinum- or Fluoropyrimidine-Containing Combination Therapy
• Date of first enrolment: August 2009
• Target sample size: 355
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00917384
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Bosnia and Herzegovina, Brazil, Canada, Chile, Colombia, Croatia, Czech Republic, Czechia, Egypt, Guatemala, India, Indonesia, Italy, Korea, Republic of, Lebanon, Malaysia, Malta, Mexico, New Zealand, Philippines, Poland, Romania, Russian Federation, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically or cytologically confirmed gastric carcinoma, including gastric
adenocarcinoma or GEJ adenocarcinoma

- Metastatic disease or locally recurrent, unresectable disease with measurable lymph
node metastases

- Measurable disease and/or evaluable disease. Measurable disease is defined as at least
one unidimensionally-measurable target lesion [= 2 centimeter (cm) with conventional
techniques or = 1 cm by spiral computed tomography (CT)], as defined by Response using
Response Evaluation Criteria in Solid Tumors (RECIST).

Examples of evaluable, nonmeasurable disease include gastric, peritoneal, or mesenteric
thickening in areas of known disease, or peritoneal nodules that are too small to be
considered measurable by RECIST

- Experienced disease progression during or within 4 months after the last dose of
first-line therapy for metastatic disease, or during or within 6 months after the last
dose of adjuvant therapy

- Disease is not amenable to potentially curative resection

- Participant is = 18 years of age

- Participant has a life expectancy of = 12 weeks

- Participant resolution to Grade = 1 (or to Grade = 2 in the case of neuropathy) by the
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE),
Version 3.0, of all clinically significant toxic effects of prior chemotherapy,
surgery, radiotherapy, or hormonal therapy (with the exception of alopecia)

- Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1

- The participant has adequate hepatic function as defined by a total bilirubin = 1.5
milligrams/deciliter (mg/dL) [25.65 micromole/liter (µmol/L)], and aspartate
transaminase (AST) and alanine transaminase (ALT) = 3.0 x the upper limit of normal
(ULN) [or 5.0 x the ULN in the setting of liver metastases]

- The participant has adequate renal function as defined by a serum creatinine = 1.5 x
the ULN, or creatinine clearance (measured via 24-hour urine collection) = 40
milliliters/minute (mL/min) (that is, if serum creatinine is > 1.5 x the ULN, a
24-hour urine collection to calculate creatinine clearance must be performed)

- The participant's urinary protein is = 1+ on dipstick or routine urinalysis ([UA]; if
urine dipstick or routine analysis is = 2+, a 24-hour urine collection for protein
must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation
in the study)

- The participant has adequate hematologic function, as evidenced by an absolute
neutrophil count (ANC) = 1000 microliters (µL), hemoglobin = 9 grams/deciliter (g/dL)
[5.58 millimoles/liter (mmol/L)], and platelets = 100,000/µL

- The participant must have adequate coagulation function as defined by International
Normalized Ratio (INR) = 1.5 and a partial thromboplastin time (PTT) = 5 seconds above
the ULN (unless receiving anticoagulation therapy). Participant on anticoagulation
therapy with unresected primary tumors or local tumor recurrence following resection
are not eligible

- If the participant has received prior anthracycline therapy as part of his or her
first-line regimen, the participant is able to engage in ordinary physical activity
without significant fatigue or dyspnea

- Because the teratogenicity of IMC-1121B is not known, the participant, if sexually
active, must be postmenopausal, surgically sterile, or using effective contraception
(hormonal or barrier methods)

- Female participant of childbearing potential must have a negative serum pregnancy test
within 7 days prior to randomization

- Able to provide informed written consent and is amenable to compliance with protocol
schedules and testing

Exclusion Criteria:

- Documented and/or symptomatic brain or leptomeningeal metastases

- Experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to
randomization

- Experienced any arterial thromboembolic events, including but not limited to
myocardial infarction, transient ischemic attack, cerebrovascular accident, or
unstable angina, within 6 months prior to randomization

- Ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic
or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the
opinion of the investigator

- Ongoing or active psychiatric illness or social situation that would limit compliance
with study requirements

- Uncontrolled or poorly-controlled hypertension despite standard medical management

- Participant has a serious or nonhealing wound, ulcer, or bone fracture

- Received chemotherapy, radiotherapy, immunotherapy, or targeted therapy for gastric
cancer within 2 weeks prior to randomization

- Received any investigational therapy within 30 days prior to randomization

- Undergone major surgery within 28 days prior to randomization, or subcutaneous venous
access device placement within 7 days prior to randomization

- Received prior therapy with an agent that directly inhibits vascular endothelial
growth factor (VEGF) or VEGF receptor 2 (R-2) activity (including bevacizumab), or any
antiangiogenic agent

- Receiving chronic antiplatelet therapy, including aspirin, nonsteroidal
anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others),
dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use [maximum dose
325 milligram/day (mg/day)] is permitted

- Participant has elective or planned major surgery to be performed during the course of
the clinical trial

- Participant has a known allergy to any of the treatment components

- Pregnant or lactating

- Known to be positive for infection with the human immunodeficiency virus

- Known alcohol or drug dependency

- Participant has a concurrent active malignancy other than adequately-treated
nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A
participant with previous history of malignancy is eligible, provided that he/she has
been free of disease for > 3 years



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Gastric Cancer

Adenocarcinoma

Intervention(s)

Biological: ramucirumab

Drug: Placebo

Other: Best Supportive Care (BSC)

Primary Outcome(s)

Overall Survival (OS) [Time Frame: Randomization up to 28 months post-randomization]

Secondary Outcome(s)

Percentage of Participants Who Are Progression-Free at Week 12 (PFS Rate) [Time Frame: Week 12 post-randomization]

Progression-Free Survival (PFS) [Time Frame: Randomization up to 17 months]

Duration of Response (DOR) [Time Frame: Randomization up to 17 months post-randomization]

Maximum Concentration (Cmax) of IMC-1121B [Time Frame: 6 weeks post-randomization]

Number of Participants With Adverse Events [Time Frame: Randomization up to 18 months]

Percentage of Participants With Objective Response (Objective Response Rate [ORR]) [Time Frame: Randomization up to 17 months post-randomization]

Change From Baseline in Quality of Life (QoL) as Measured by the European Organisation for Research and Treatment of Cancer Questionnaire (EORTC-QLQ-C30) [Time Frame: Baseline up to Cycle 10 (18 weeks [1 cycle=2 weeks])]

Number of Participants Who Developed Antibodies Against IMC-1121B [Time Frame: Baseline, 12 Weeks]

Secondary ID(s)

CP12-0715

2008-005964-15

13893

I4T-IE-JVBD

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/10/2014
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00917384