Phase III Study of Docetaxel + Ramucirumab or Placebo in Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00703326
First received: June 20, 2008
Last updated: March 14, 2014
Last verified: March 2014
  Purpose

The objective of this study is to compare the progression-free survival (PFS) of the drug combination ramucirumab plus docetaxel to placebo plus docetaxel in previously untreated participants with human epidermal growth factor receptor 2 (HER2)-negative, unresectable, locally-recurrent or metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: ramucirumab (IMC-1121B)
Drug: docetaxel
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Multinational, Randomized, Double-Blind, Phase III Study of IMC-1121B Plus Docetaxel Versus Placebo Plus Docetaxel in Previously Untreated Patients With HER2-Negative, Unresectable, Locally-Recurrent or Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is measured from the date of randomization to the first documented date of disease progression or death from any cause.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    Overall survival is measured as the interval from randomization to the date of death from any cause.

  • Time to Progression (TTP) [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    Time to progression is the interval from the date of randomization to the first documented date of disease progression.

  • Percentage of Participants with Objective Response (Objective Response Rate) [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    The percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR).

  • Duration of Response [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    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.

  • Total Functional Assessment of Cancer Therapy -Breast (FACT-B): Change From Baseline to End of Therapy [ Time Frame: up to 36 months ] [ Designated as safety issue: No ]
    FACT-B measures the following domains of health-related quality of life (HR-QL): physical well-being (PWB), social/family well-being (SFWB), emotional well-being (EWB), functional well-being (FWB), & additional concerns of breast cancer (BCS). Total FACT-B scores range from 0-144, with higher scores representing better HR-QOL.


Enrollment: 1144
Study Start Date: August 2008
Estimated Study Completion Date: August 2015
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ramucirumab (IMC-1121B) + docetaxel Biological: ramucirumab (IMC-1121B)
Ramucirumab (IMC-1121B) is administered at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Other Names:
  • IMC-1121B
  • LY3009806
Drug: docetaxel
Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Placebo Comparator: placebo + docetaxel Drug: docetaxel
Docetaxel is administered at a dose of 75 milligrams per square meter (mg/m²) as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Other: placebo
Placebo comparator for ramucirumab (IMC-1121B) administered at a dose of 10 mg/kg as a 1-hour intravenous infusion on Day 1 of each 21-day cycle.
Other Name: placebo

Detailed Description:

Female participants at least 18 years of age with histologically or cytologically confirmed, human epidermal growth factor receptor 2 (HER2) negative breast adenocarcinoma that is metastatic or locally-recurrent and inoperable with curative intent will be randomized. Participants may not have received chemotherapy for metastatic or locally-recurrent, inoperable breast cancer.

It is anticipated that 1113 participants will be randomized with 371 participants in the docetaxel plus placebo arm and 742 participants in the docetaxel plus ramucirumab (IMC-1121B) arm. There will be approximately 250 centers in North and South America, Europe, Asia, Middle East, Africa, Australia, and New Zealand.

On Day 1 of each 21-day cycle, participants will receive docetaxel 75 mg/m² as a one-hour I.V. infusion followed by either ramucirumab (IMC-1121B) 10 mg/kg or placebo 10 mg/kg as a one-hour I.V. infusion. Each cycle is repeated every 21 days.

Treatment will continue until there is evidence of progressive disease, unacceptable toxicity, or other withdrawal criteria are met. Participants who discontinue study treatment with either ramucirumab (IMC-1121B) or placebo may continue to receive docetaxel. Similarly, participants who discontinue docetaxel therapy may continue to receive either ramucirumab (IMC-1121B) or placebo, whichever the participant was randomized to receive. All participants will be followed for survival at regularly scheduled intervals (every 6 weeks until progressive disease and every 6 months thereafter) for at least 36 months after discontinuing study therapy.

  Eligibility

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

Inclusion Criteria:

  • Participant is able to provide signed informed consent
  • Participant is female and ≥ 18 years of age or older if required by local laws or regulations
  • Participant has histologically or cytologically confirmed adenocarcinoma of the breast that is now metastatic or locally-recurrent and inoperable with curative intent. Every effort should be made to make paraffin-embedded tissue or slides from the diagnostic biopsy or surgical specimen available for confirmation of diagnosis
  • Participant has measurable and/or non-measurable disease
  • Participants' primary and/or metastatic tumor is human epidermal growth factor receptor 2 (HER2)-negative by fluorescence in-situ hybridization (FISH) or chromogenic in-situ hybridization (CISH) or 0, 1+ overexpression by immunohistochemistry (IHC)
  • Participant has not received prior chemotherapy for metastatic or locally-recurrent and inoperable breast cancer
  • Participant completed (neo) adjuvant taxane therapy at least 6 months prior to randomization
  • Participant completed (neo) adjuvant biologic therapy at least 6 weeks prior to randomization
  • Participant completed all prior radiotherapy with curative intent ≥ 3 weeks prior to randomization
  • Participant may have received prior hormonal therapy for breast cancer in the (neo) adjuvant and/or the metastatic setting ≥ 2 weeks prior to randomization
  • Participant's left ventricular ejection fraction is within normal institutional ranges
  • Participant has resolution to grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3 (NCI-CTCAE v 3.0) of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy which must have resolved to grade ≤ 2
  • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Participant is amenable to compliance with protocol schedules and testing
  • Participant has adequate hematological functions [absolute neutrophil count (ANC) ≥ 1500 cells/microliter (mcL), hemoglobin ≥ 9 grams/deciliter (g/dL), and platelets ≥ 100,000 cells/mcL and ≤ 850,000 cells/mcL]
  • Participant has adequate hepatic function [bilirubin within normal limits (WNL), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times the upper limit of normal (ULN), or ≤ 5.0 times the ULN if the transaminase elevation is due to liver metastases, and alkaline phosphatase ≤ 5.0 times the ULN]
  • Participant has serum creatinine ≤ 1.5 x ULN. If serum creatinine > 1.5 x ULN the calculated creatinine clearance should be > 40 milliliters/minute (mL/min)
  • Participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA); if urine protein ≥ 2+, a 24-hour urine collection must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study
  • Participant must have adequate coagulation function as defined by international normalized ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 1.5 X ULN if not receiving anticoagulation therapy. Participants on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight heparin and if on warfarin must have a INR between 2 and 3 and have no active bleeding (defined as within 14 days of randomization) or pathological condition that carries a high risk of bleeding (such as, tumor involving major vessels or known varices)
  • Women of childbearing potential must implement adequate contraception in the opinion of the investigator
  • Participant has not received prior biologic therapy for metastatic or locally recurrent and inoperable breast cancer

Exclusion Criteria:

  • Participant has a concurrent active malignancy other than breast adenocarcinoma, adequately treated non melanomatous skin cancer, or other non-invasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that she has been disease free for > 3 years
  • Participant has a known sensitivity to docetaxel or other drugs formulated with polysorbate 80
  • Participant has a known sensitivity to agents of similar biologic composition as ramucirumab or other agents that specifically target vascular endothelial growth factor (VEGF)
  • Participant has a history of chronic diarrheal disease within 6 months prior to randomization
  • Participant has received irradiation to a major bone marrow area as defined as > 25% of bone marrow (such as, pelvic or abdominal radiation) within 30 days prior to randomization
  • Participant has participated in clinical trials of experimental agents within 4 weeks prior to randomization
  • Participant has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
  • Participant has active, high risk bleeding (such as, via gastric ulcers or gastric varices) within 14 days prior to randomization
  • Participant has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
  • Participant has uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator
  • Participant has brain metastases, uncontrolled spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
  • Participant has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
  • Participant has pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
  • Participant is pregnant or lactating
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00703326

  Show 234 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: NCT00703326     History of Changes
Other Study ID Numbers: 13892, 2008-001727-65, TRIO-012, TRIO-CIRG-012, CP12-0606, I4T-IE-JVBC
Study First Received: June 20, 2008
Last Updated: March 14, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: Ministry of Health
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Egypt: Ministry of Health and Population
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Germany: Paul-Ehrlich-Institut
Ireland: Irish Medicines Board
Israel: Ministry of Health
New Zealand: Medsafe
Peru: Instituto Nacional de Salud
Poland: Ethics Committee
Poland: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Metastatic breast cancer
HER2 negative breast cancer
locally recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014