Study investigating new drug, IMC-1121B, in patients with advanced cancer of the stomach/oesophagus that has grown despite standard chemotherapy (combination of chemotherapy including platinum or fluoropyrimidine). Study has two arms. Patients will be assigned "randomly" to either arm: Arm1: 2/3 of patients receive IMC-1121B and best supportive care; Arm2: 1/3 receive an inactive substance (placebo) and best supportive care. Neither the patient nor the doctor will know the treatment arm.

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2008-005964-15-GB
• Date of registration: 15/03/2010
• Prospective Registration: No
• Primary sponsor: ImClone LLC
• Public title: Study investigating new drug, IMC-1121B, in patients with advanced cancer of the stomach/oesophagus that has grown despite standard chemotherapy (combination of chemotherapy including platinum or fluoropyrimidine). Study has two arms. Patients will be assigned "randomly" to either arm: Arm1: 2/3 of patients receive IMC-1121B and best supportive care; Arm2: 1/3 receive an inactive substance (placebo) and best supportive care. Neither the patient nor the doctor will know the treatment arm.
• 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: 09/02/2010
• Target sample size: 348
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005964-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Brazil, Canada, Chile, Colombia, Czech Republic, Egypt, European Union, India, Indonesia, Italy, Jordan, Korea, Republic of, Lebanon, Malaysia, Malta, Mexico, New Zealand, Philippines, Russian Federation, Spain, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: Clinical Trials Info
• Affiliation: ImClone Systems International GmbH

• Name: Clinical Trials Info
• Affiliation: ImClone Systems International GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
Each patient must meet the following criteria to be enrolled in this study.
1. Histologically- or cytologically-confirmed gastric carcinoma, including gastric adenocarcinoma or GEJ adenocarcinoma.
2. Metastatic disease or locally recurrent, unresectable disease with measurable lymph node metastases.
3. Measurable disease and/or evaluable disease. Measurable disease is defined as at least one unidimensionally-measurable target lesion (= 2 cm with conventional techniques or = 1 cm by spiral CT), as defined by 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.
4. 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.
5. Disease is not amenable to potentially curative resection.
6. Patient is = 18 years of age.
7. Patient has a life expectancy of = 12 weeks.
8. Patient 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).
9. ECOG PS score of 0-1.
10. The patient has adequate hepatic function as defined by a total bilirubin = 1.5 mg/dL (25.65 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].
11. The patient 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 mL/minute (ie, if serum creatinine is > 1.5 x the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed).
12. The patient'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 mg of protein in 24 hours to allow participation in the study).
13. The patient has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) = 1000/µL, hemoglobin = 9 g/dL (5.58 mmol/L), and platelets = 100,000/µL.
14. The patient 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). Patients on anticoagulation therapy with unresected primary tumors or local tumor recurrence following resection are not eligible.
15. If the patient has received prior anthracycline therapy as part of his or her first-line regimen, the patient is able to engage in ordinary physical activity without significant fatigue or dyspnea.
16. Because the teratogenicity of IMC-1121B is not known, the patient, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods).
17. F
Exclusion criteria:
Patients who meet any of the following criteria will be excluded from the study.
1. Documented and/or symptomatic brain or leptomeningeal metastases.
2. Experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to randomization.
3. 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.
4. 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.
5. Ongoing or active psychiatric illness or social situation that would limit compliance with study requirements.
6. Uncontrolled or poorly-controlled hypertension despite standard medical management.
7. Patient has a serious or nonhealing wound, ulcer, or bone fracture.
8. Received chemotherapy, radiotherapy, immunotherapy, or targeted therapy for gastric cancer within 2 weeks prior to randomization.
9. Received any investigational therapy within 30 days prior to randomization.
10. Undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization.
11. Received prior therapy with an agent that directly inhibits VEGF or VEGFR-2 activity (including bevacizumab), or any antiangiogenic agent.
12. 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 mg/day) is permitted.
13. Patient has elective or planned major surgery to be performed during the course of the clinical trial.
14. Patient has a known allergy to any of the treatment components.
15. Pregnant or lactating.
16. Known to be positive for infection with the human immunodeficiency virus.
17. Known alcohol or drug dependency.
18. Patient has a concurrent active malignancy other than adequately-treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A patient with previous history of malignancy is eligible, provided that he/she has been free of disease for > 3 years.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Metastatic Gastric Cancer
MedDRA version: 14.1 Level: PT Classification code 10063916 Term: Metastatic gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: ramucirumab
Product Code: IMC-1121B
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Ramucirumab
CAS Number: 947 687-13-0
Current Sponsor code: IMC-1121B
Other descriptive name: recombinant human IgG1 monoclonal antibody (MAb)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): (1) Overall Survival (OS):

Overall survival is defined as the time from the date of randomization to the date of death from any cause.

Secondary Objective: - To evaluate the progression-free survival (PFS), including 12-week PFS rate,
associated with IMC-1121B versus placebo
- To evaluate the objective response rate (ORR)
- To evaluate the duration of response
- To evaluate the quality of life (QoL)
- To evaluate the safety profile of IMC-1121B
- To examine the pharmacodynamic profile of IMC-1121B
- To assess the immunogenicity of IMC-1121B

Timepoint(s) of evaluation of this end point: (1) Date of death from any cause captured per patient

Main Objective: To evaluate the overall survival (OS) of patients with metastatic gastric cancer (including adenocarcinomas of the gastroesophageal junction [GEJ]) following disease progression on first-line platinum- or fluoropyrimidine-containing combination chemotherapy who undergo treatment with the MAb IMC-1121B plus BSC versus placebo plus BSC.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Timepoints of evaluation after randomization captured by patient:

(1)-(3), (8): PFS, ORR, DOR, Imaging (CT/MRI)/tumor assessment: baseline, every 6 weeks, end of therapy

(4) EORTC-QLQ-C30: baseline, every 6 weeks

(5) AE: baseline, every two weeks, end of therapy, 30-day follow-up

(6) PD: baseline, week 4, week 8, end of therapy, 30-day follow-up

(7) Immunogenicity: baseline, every 6 weeks, 30-day follow-up

Secondary end point(s): (1) Proportion of Participants Who are Progression-free (PFS) at Week 12:
The 12-week progression-free survival (PFS) rate is defined as the proportion of participants that are alive and progression-free 12 weeks after randomization.

(2) Proportion of Participants with Objective Response (Objective Response Rate):
The objective response rate (ORR) is equal to the proportion of participants achieving a best overall response of partial or complete response (PR + CR).

(3) Duration of Response: Duration of response is the interval from date of initial documented response (complete response or partial response) to the first documented date of disease progression or death.

(4) Change from Baseline in Quality of Life (QoL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC-QLQ-C30) Survey.

(5) Number of Participants with Adverse Events.

(6) Pharmacodynamics (PD): Maximum concentration (Cmax) of IMC-1121B

(7) Change from Baseline in Antibodies against IMC-1121B.

(8) Progression-free Survival (PFS). Progression-free survival (PFS) is defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever is first.

Secondary ID(s)

2008-005964-15-IT

IMCLCP12-0715

Source(s) of Monetary Support

ImClone Systems Corporation, a wholly-owned subsidiary of Eli Lilly and Company

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 24/12/2016
• Date Completed: 17/12/2015
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-005964-15/results