Clinical trial NCT00917384: Study of IMC-1121B (Ramucirumab) With Best Supportive Care in Participants With Gastric Cancer and Adenocarcinoma
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Cancer
Adenocarcinoma
Keywords: IMC-1121B
Monoclonal antibody (MAb)
Vascular endothelial growth factor (VEGF)
Human vascular endothelial growth factor receptor-2 (VEGFR-2)
Platinum resistant
platinum refractory
Gastric
Gastroesophageal Junction Adenocarcinoma
metastatic
Angiogenesis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-06-10
Enrollment: 355
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to gather information about the use of an investigational drug called Ramucirumab in adenocarcinomas of the stomach or gastroesophageal junction.

Detailed description: Placebo-controlled, multicenter Phase 3 study of participants with metastatic gastric cancer \[including adenocarcinomas of the gastroesophageal junction (GEJ)\] and disease progression on standard first-line chemotherapeutic regimens. Participants will be randomized on a 2:1 basis to receive best supportive care plus ramucirumab administered every 2 weeks or best supportive care plus placebo administered every 2 weeks, respectively. Participants will undergo radiographic assessment of disease status every 6 weeks. Participant will be treated until there is evidence of progressive disease, toxicity requiring cessation, withdrawal of consent, or until other withdrawal criteria are met.

Approximately 348 participants, with histologically- or cytologically-confirmed, metastatic gastric or GEJ adenocarcinoma, and radiographically measurable disease as defined by the Response Evaluation Criteria in Solid Tumors or evaluable, nonmeasurable disease, will be randomized. Participants will be enrolled from approximately 250 study centers in North America, South America, Central America, Asia, Australia, New Zealand, and Europe.

Eligibility 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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Randomization up to 28 months post-randomization
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Randomization up to 17 months
measure: Percentage of Participants Who Are Progression-Free at Week 12 (PFS Rate)
timeFrame: Week 12 post-randomization
measure: Percentage of Participants With Objective Response (Objective Response Rate [ORR])
timeFrame: Randomization up to 17 months post-randomization
measure: Duration of Response (DOR)
timeFrame: Randomization up to 17 months post-randomization
measure: Change From Baseline in Quality of Life (QoL) as Measured by the European Organisation for Research and Treatment of Cancer Questionnaire (EORTC-QLQ-C30)
timeFrame: Baseline up to Cycle 10 (18 weeks [1 cycle=2 weeks])
measure: Number of Participants With Adverse Events
timeFrame: Randomization up to 18 months
measure: Maximum Concentration (Cmax) of IMC-1121B
timeFrame: 6 weeks post-randomization
measure: Number of Participants Who Developed Antibodies Against IMC-1121B
timeFrame: Baseline, 12 Weeks
Other outcomes:
Locations:
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city: Slavonski Brod
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city: Zagreb
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city: Brno
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city: Hradec Kralove
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city: Cluj Napoca
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city: Suceava
country: Romania
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city: Chelyabinsk
country: Russian Federation
facility: ImClone Investigational Site
city: Kursk
country: Russian Federation
facility: ImClone Investigational Site
city: Moscow
country: Russian Federation
facility: ImClone Investigational Site
city: Moscow
country: Russian Federation
facility: ImClone Investigational Site
city: Pyatigorsk
country: Russian Federation
facility: ImClone Investigational Site
city: St. Petersburg
country: Russian Federation
facility: ImClone Investigational Site
city: St. Petersburg
country: Russian Federation
facility: ImClone Investigational Site
city: St. Petersburg
country: Russian Federation
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city: Cape Town
country: South Africa
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city: Alcorcon
country: Spain
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city: Barcelona
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city: Barcelona
country: Spain
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city: Elche
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city: Madrid
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city: Santander
country: Spain
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city: Sevilla
country: Spain
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city: Kaohsiung
country: Taiwan
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city: Taichung County
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city: Taipei
country: Taiwan
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city: Taipei
country: Taiwan
facility: ImClone Investigational Site
city: Bangkok
country: Thailand
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city: Chiang Mai
country: Thailand
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city: Rajathevee District
country: Thailand
facility: ImClone Investigational Site
city: Adana
country: Turkey
facility: ImClone Investigational Site
city: Gaziantep
country: Turkey
facility: ImClone Investigational Site
city: Istanbul
country: Turkey
facility: ImClone Investigational Site
city: Izmir
country: Turkey
facility: ImClone Investigational Site
city: Bebington
country: United Kingdom
facility: ImClone Investigational Site
state: Wirral
city: London
country: United Kingdom
facility: ImClone Investigational Site
city: Sutton
country: United Kingdom
facility: ImClone Investigational Site
city: Wolverhampton
country: United Kingdom
facility: ImClone Investigational Site
Study officials:
affiliation: Eli Lilly and Company
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)
role: STUDY_DIRECTOR
References:
citation: Chau I, Fuchs CS, Ohtsu A, Barzi A, Liepa AM, Cui ZL, Hsu Y, Al-Batran SE. Association of quality of life with disease characteristics and treatment outcomes in patients with advanced gastric cancer: Exploratory analysis of RAINBOW and REGARD phase III trials. Eur J Cancer. 2019 Jan;107:115-123. doi: 10.1016/j.ejca.2018.11.013. Epub 2018 Dec 14.
citation: Tabernero J, Ohtsu A, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Ajani JA, Tomasek J, Safran H, Chandrawansa K, Hsu Y, Heathman M, Khan A, Ni L, Melemed AS, Gao L, Ferry D, Fuchs CS. Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer. Mol Cancer Ther. 2017 Oct;16(10):2215-2222. doi: 10.1158/1535-7163.MCT-16-0895. Epub 2017 Jul 17.
citation: Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, Dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-39. doi: 10.1016/S0140-6736(13)61719-5. Epub 2013 Oct 3.