Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients

NCT ID: NCT01234402

Last Updated: 2019-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2017-07-31

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ramucirumab DP + Capecitabine

Cycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.

Group Type: EXPERIMENTAL

Ramucirumab DP

Intervention Type: BIOLOGICAL

10 mg/kg I.V.

Day 1 of every-21-day cycle

Capecitabine

Intervention Type: DRUG

1000 mg/m^2 orally

Twice a day for 14 days

Icrucumab + Capecitabine

Cycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.

Group Type: EXPERIMENTAL

IMC-18F1

Intervention Type: BIOLOGICAL

12 mg/kg I.V.

Days 1 and 8 of every-21-day cycle

Capecitabine

Intervention Type: DRUG

1000 mg/m^2 orally

Twice a day for 14 days

Capecitabine*

Crossover 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.

Group Type: ACTIVE_COMPARATOR

Capecitabine

Intervention Type: DRUG

1000 mg/m^2 orally

Twice a day for 14 days

Interventions

Ramucirumab DP

10 mg/kg I.V.

Day 1 of every-21-day cycle

Intervention Type: BIOLOGICAL

IMC-18F1

12 mg/kg I.V.

Days 1 and 8 of every-21-day cycle

Intervention Type: BIOLOGICAL

Capecitabine

1000 mg/m^2 orally

Twice a day for 14 days

Intervention Type: DRUG

Other Intervention Names

IMC-1121B; LY3009806; Icrucumab; LY3012212

Eligibility Criteria

Inclusion Criteria

• 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
• Has urinary protein is ≤ 1+ on dipstick or routine urinalysis; if urine protein ≥ 2+, a 24-hour urine collection must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study
• Agrees to use adequate contraception during the study period and for 12 weeks after the last dose of study medication

Exclusion Criteria

• 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
• Has brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease
• Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
• Has received a prior allogeneic organ or tissue transplantation
• Has undergone major surgery within 4 weeks prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization
• Has had a serious nonhealing wound, ulcer, or bone fracture within 4 weeks prior to randomization
• Has known HIV or AIDS infection
• Has an elective or planned major surgery to be performed during the course of the trial
• Participant is pregnant or lactating

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Eli Lilly and Company

Locations

ImClone Investigational Site

Scottsdale, Arizona, United States

ImClone Investigational Site

Los Angeles, California, United States

ImClone Investigational Site

Jacksonville, Florida, United States

ImClone Investigational Site

Atlanta, Georgia, United States

ImClone Investigational Site

Augusta, Georgia, United States

ImClone Investigational Site

Chicago, Illinois, United States

ImClone Investigational Site

Indianapolis, Indiana, United States

ImClone Investigational Site

Baton Rouge, Louisiana, United States

ImClone Investigational Site

New York, New York, United States

ImClone Investigational Site

Stony Brook, New York, United States

ImClone Investigational Site

The Bronx, New York, United States

ImClone Investigational Site

Washington, North Carolina, United States

ImClone Investigational Site

Cincinnati, Ohio, United States

ImClone Investigational Site

Columbus, Ohio, United States

ImClone Investigational Site

Dallas, Texas, United States

ImClone Investigational Site

San Antonio, Texas, United States

ImClone Investigational Site

Salt Lake City, Utah, United States

ImClone Investigational Site

Richmond, Virginia, United States

ImClone Investigational Site

Spokane, Washington, United States

ImClone Investigational Site

Morgantown, West Virginia, United States

ImClone Investigational Site

Calgary, Alberta, Canada

ImClone Investigational Site

Edmonton, Alberta, Canada

ImClone Investigational Site

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 28220020 (View on PubMed)

Other Identifiers

CP20-0903

Identifier Type: OTHER

Identifier Source: secondary_id

I4Y-IE-JCDD

Identifier Type: OTHER

Identifier Source: secondary_id

13944

Identifier Type: -

Identifier Source: org_study_id