Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients
An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Ramucirumab (IMC-1121B) Drug Product or Icrucumab (IMC-18F1) in Combination With Capecitabine or Capecitabine Monotherapy, in Unresectable, Locally Advanced or Metastatic Breast Cancer Patients Previously Treated With Anthracycline and Taxane Therapy
3 other identifiers
interventional
153
2 countries
23
Brief Summary
An open-label, multicenter, randomized, Phase 2 trial in which participant with unresectable, locally advanced or metastatic breast cancer who have been previously treated with anthracycline and taxane therapy receive ramucirumab DP or Icrucumab (IMC-18F1) administered on an every-21-day cycle (in combination with oral capecitabine therapy; capecitabine is administered twice a day on Days 1-14 of each cycle). Approximately 150 participants will be randomized in a 1:1:1 ratio to either ramucirumab DP or Icrucumab (IMC-18F1) in combination with capecitabine (Arm A and Arm B, respectively) or capecitabine monotherapy (Arm C). Randomization will be stratified by triple-negative receptor status (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor-2 \[HER2/neu\]-negative) (yes/no) and receipt of prior antiangiogenic therapy. Treatment with the study medication(s) will continue until disease progression, the development of unacceptable toxicity, noncompliance or withdrawal of consent by the participant, or investigator decision. Capecitabine dose reductions in the setting of significant myelosuppression, hand-and-foot syndrome, or diarrhea will be required.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 breast-cancer
Started Mar 2011
Typical duration for phase_2 breast-cancer
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 3, 2010
CompletedFirst Posted
Study publicly available on registry
November 4, 2010
CompletedStudy Start
First participant enrolled
March 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2017
CompletedResults Posted
Study results publicly available
August 14, 2019
CompletedAugust 14, 2019
July 1, 2019
2.6 years
November 3, 2010
June 13, 2019
July 21, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-Free Survival (PFS)
PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause, whichever is first. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 millimeter (mm) and the appearance of ≥1 new lesions was progression. Participants who did not progress, were lost to follow-up, or had missed 2 or more scheduled tumor assessments were censored at the day of their last adequate tumor assessment.
From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
Secondary Outcomes (12)
Overall Survival (OS)
From Date of Randomization until Death Due to Any Cause (Up To 160 weeks)
Percentage of Participants With Objective Response Rate (ORR)
From Date of Randomization until Disease Progression/Recurrence (Up to 97 weeks)
Duration of Response
From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 97 weeks)
Number of Participants With Adverse Events (AEs)
Up To 160 Weeks
Number of Participants With Serious Adverse Events (SAEs)
Up To 160 Weeks
- +7 more secondary outcomes
Study Arms (3)
Ramucirumab DP + Capecitabine
EXPERIMENTALCycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
Icrucumab + Capecitabine
EXPERIMENTALCycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
Capecitabine*
ACTIVE COMPARATORCrossover Study: \* At the discretion of the investigator, participants will be eligible to receive either ramucirumab DP or Icrucumab (IMC-18F1) in combination with capecitabine, after radiographic disease progression while on capecitabine. The investigator will decide which investigational product will be given. Cycles repeat every 21 days until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
Interventions
10 mg/kg I.V. Day 1 of every-21-day cycle
12 mg/kg I.V. Days 1 and 8 of every-21-day cycle
1000 mg/m\^2 orally Twice a day for 14 days
Eligibility Criteria
You may qualify if:
- The participant has histologically or cytologically confirmed breast cancer which at the time of study entry is either Stage III disease not amenable to curative therapy or Stage IV disease
- Has measurable or nonmeasurable disease
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Has received prior anthracycline therapy
- Has received prior taxane therapy
- Participants with human epidermal growth factor receptor-2 (HER2) positive disease must have progressed on or following trastuzumab
- Participants with hormone receptor-positive disease must have progressed on or following hormone therapy
- Has received ≤ 3 prior chemotherapy regimens in any setting (a regimen is defined as any agent\[s\] that has been administered for more than 1 cycle; sequential neoadjuvant/adjuvant treatment is considered 1 regimen)
- Has completed any prior radiotherapy ≥ 4 weeks prior to randomization
- Has completed any prior hormonal therapy ≥ 2 weeks prior to randomization
- Has adverse events (AEs) that have resolved to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0) from all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy,or hormonal therapy
- Has adequate hematologic, coagulation, hepatic and renal function
- Does not have:
- cirrhosis at a level of Child-Pugh B (or worse) or
- cirrhosis (any degree) and a history of hepatic encephalopathy or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
- +2 more criteria
You may not qualify if:
- Has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, curatively treated cervical carcinoma in situ, or other noninvasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that there has been a disease-free interval for \> 3 years
- Has a known sensitivity to capecitabine, any of its components, or other drugs formulated with polysorbate 80
- Has a known sensitivity to 5-fluorouracil (5-FU)
- Has a known dihydropyrimidine dehydrogenase deficiency
- Has received prior capecitabine treatment for advanced breast cancer
- Has received investigational therapy within 2 weeks prior to randomization
- Has received bevacizumab within 4 weeks prior to randomization
- Has received more than 1 prior antiangiogenic agent for breast cancer
- Has a known sensitivity to agents of similar biologic composition as ramucirumab DP or Icrucumab (IMC-18F1), or other agents that specifically target vascular endothelial growth factor (VEGF)
- Has an acute/subacute bowel obstruction or history of chronic diarrhea requiring ongoing medical intervention
- Has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
- Has experienced a Grade ≥ 3 bleeding event within 3 months prior to randomization
- Is receiving prophylactic or therapeutic anticoagulation with warfarin or any other oral anticoagulant
- Has an uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, symptomatic anemia, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorder in the opinion of the investigator
- Has experienced any arterial thrombotic or thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident within 6 months prior to randomization
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
ImClone Investigational Site
Scottsdale, Arizona, 85259, United States
ImClone Investigational Site
Los Angeles, California, 90033, United States
ImClone Investigational Site
Jacksonville, Florida, 32224, United States
ImClone Investigational Site
Atlanta, Georgia, 30322, United States
ImClone Investigational Site
Augusta, Georgia, 30912, United States
ImClone Investigational Site
Chicago, Illinois, 60611, United States
ImClone Investigational Site
Indianapolis, Indiana, 46202, United States
ImClone Investigational Site
Baton Rouge, Louisiana, 70809, United States
ImClone Investigational Site
New York, New York, 10021, United States
ImClone Investigational Site
Stony Brook, New York, 11794, United States
ImClone Investigational Site
The Bronx, New York, 10461, United States
ImClone Investigational Site
Washington, North Carolina, 27889, United States
ImClone Investigational Site
Cincinnati, Ohio, 45242, United States
ImClone Investigational Site
Columbus, Ohio, 43219, United States
ImClone Investigational Site
Dallas, Texas, 75390, United States
ImClone Investigational Site
San Antonio, Texas, 78229, United States
ImClone Investigational Site
Salt Lake City, Utah, 84106, United States
ImClone Investigational Site
Richmond, Virginia, 23230, United States
ImClone Investigational Site
Spokane, Washington, 99208, United States
ImClone Investigational Site
Morgantown, West Virginia, 26506, United States
ImClone Investigational Site
Calgary, Alberta, T2N 4N2, Canada
ImClone Investigational Site
Edmonton, Alberta, T6G 1Z2, Canada
ImClone Investigational Site
Toronto, Ontario, M4N 3M5, Canada
Related Publications (1)
Vahdat LT, Layman R, Yardley DA, Gradishar W, Salkeni MA, Joy AA, Garcia AA, Ward P, Khatcheressian J, Sparano J, Rodriguez G, Tang S, Gao L, Dalal RP, Kauh J, Miller K. Randomized Phase II Study of Ramucirumab or Icrucumab in Combination with Capecitabine in Patients with Previously Treated Locally Advanced or Metastatic Breast Cancer. Oncologist. 2017 Mar;22(3):245-254. doi: 10.1634/theoncologist.2016-0265. Epub 2017 Feb 20.
PMID: 28220020DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
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)
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 3, 2010
First Posted
November 4, 2010
Study Start
March 1, 2011
Primary Completion
October 1, 2013
Study Completion
July 1, 2017
Last Updated
August 14, 2019
Results First Posted
August 14, 2019
Record last verified: 2019-07
Data Sharing
- IPD Sharing
- Will share
Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com. This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.