Study of IMC-18F1 or Ramucirumab DP in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01234402
First received: November 3, 2010
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

An open-label, multicenter, randomized, Phase 2 trial in which patients with unresectable, locally advanced or metastatic breast cancer who have been previously treated with anthracycline and taxane therapy receive ramucirumab DP or 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 patients will be randomized in a 1:1:1 ratio to either ramucirumab DP or 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 patient, or investigator decision. Capecitabine dose reductions in the setting of significant myelosuppression, hand-and-foot syndrome, or diarrhea will be required.


Condition Intervention Phase
Breast Cancer
Biological: Ramucirumab DP
Biological: IMC-18F1
Drug: Capecitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Ramucirumab (IMC-1121B) Drug Product or 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: No ]
  • Objective Response Rate (ORR) [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events (AEs) [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: Yes ]
  • Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: Yes ]
  • Maximum Concentration (Cmax) Ramucirumab Drug Product (DP) or IMC-18F1 [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: No ]
    Cycles 1, 2, 3, 4, 6, every 2 Cycles thereafter, and at 30 day follow-up

  • Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or IMC-18F1 [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: No ]
    Cycles 1, 2, 3, 4, 6, every 2 Cycles thereafter, and at 30 day follow-up

  • Area under the curve (AUC) [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: No ]
    Cycles 1, 2, 3, 4, 6, every 2 Cycles thereafter, and at 30 day follow-up

  • Terminal half-life (t½) [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: No ]
    Cycles 1, 2, 3, 4, 6, every 2 Cycles thereafter, and at 30 day follow-up

  • Clearance (Cl) [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: No ]
    Cycles 1, 2, 3, 4, 6, every 2 Cycles thereafter, and at 30 day follow-up

  • Volume of Distribution at Steady State (Vss) [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: No ]
    Cycles 1, 2, 3, 4, 6, every 2 Cycles thereafter, and at 30 day follow-up

  • Anti-Ramucirumab and Anti-IMC-18F1 Antibody Assessment [ Time Frame: Approximately 31 Months ] [ Designated as safety issue: Yes ]
    Prior to infusion in Cycles 1, 2, 3, 6, every 2 Cycles thereafter, and at 30 day follow-up


Enrollment: 153
Study Start Date: March 2011
Estimated Study Completion Date: October 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramucirumab DP + Capecitabine
Cycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the patient.
Biological: Ramucirumab DP

10 mg/kg I.V.

Day 1 of every-21-day cycle

Other Names:
  • IMC-1121B
  • LY3009806
Drug: Capecitabine

1000 mg/m2 orally

Twice a day for 14 days

Experimental: IMC-18F1 + Capecitabine
Cycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the patient.
Biological: IMC-18F1

12 mg/kg I.V.

Days 1 and 8 of every-21-day cycle

Other Names:
  • Icrucumab
  • LY3012212
Drug: Capecitabine

1000 mg/m2 orally

Twice a day for 14 days

Active Comparator: Capecitabine*

Crossover Study:

* At the discretion of the investigator, patients will be eligible to receive either ramucirumab DP or 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 patient.

Drug: Capecitabine

1000 mg/m2 orally

Twice a day for 14 days


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient 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
  • Patients with HER2-positive disease must have progressed on or following trastuzumab
  • Patients 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 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 patient 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-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 IMC-18F1, or other agents that specifically target 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
  • Patient is pregnant or lactating
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01234402

  Show 23 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01234402     History of Changes
Other Study ID Numbers: 13944, CP20-0903, I4Y-IE-JCDD
Study First Received: November 3, 2010
Last Updated: February 27, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Eli Lilly and Company:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Fluorouracil
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2014