A Study of Ramucirumab (IMC-1121B) in Participants With Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01256567
First received: December 7, 2010
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

The primary objective of this study is to investigate the safety and tolerability of the anti-VEGFR-2 monoclonal antibody ramucirumab drug product in combination with docetaxel in Japanese participants with metastatic, or locally advanced breast cancer, with the aim of confirming the recommended dose of ramucirumab drug product (DP) in combination with docetaxel.


Condition Intervention Phase
Breast Cancer
Metastatic Breast Cancer
Biological: Ramucirumab
Drug: Docetaxel
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Study of Docetaxel in Combination With Ramucirumab (IMC-1121B) Drug Product in Patients With Locally Advanced or Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: Baseline up to data cut off (approximately 48.3 weeks) ] [ Designated as safety issue: Yes ]
    Number participants with drug related dose-limiting toxicities (DLT) during Cycle 1; ramucirumab related: treatment-emergent adverse events (TEAE), serious adverse events (SAE), Grade 3 or higher TEAE, or TEAE leading to discontinuation or ramucirumab dose modification. DLT=G4 neutropenia >7days; G ≥3 neutropenia with fever ≥38.5°C requiring IV antibiotics or bacteriemia or sepsis; G4 thrombocytopenia; G ≥3 thrombocytopenia with bleeding requiring platelets; G≥3 prothrombin time and/or partial thromboplastin time in absence of anticoagulants; G≥2 hyperbilirubinemia ≥5 days; QTc >500 milliseconds (ms) or increase ≥100 ms or arrhythmia; G≥4 or uncontrollable hypertension; G≥3 nonhematologic toxicity (excluding G3: hypersensitivity, injection-site reaction, arthralgia/myalgia, asthenia/fatigue, diarrhea without loperamide therapy, nausea/vomiting without antiemetics, transient G3/4 elevation of aminotransferases); treatment delay >2 weeks due to toxicity.


Secondary Outcome Measures:
  • Serum Anti-IMC-1121B Antibody Assessment (Immunogenicity) [ Time Frame: Baseline up to data cut off (approximately 48.3 weeks) ] [ Designated as safety issue: Yes ]
    The number of participants with a positive anti-IMC-1121B titer at any point during the study.

  • Maximum Concentration (Cmax) of Ramucirumab [ Time Frame: Day 1 of Cycle 1 and Cycle 4 (cycle=21 days) ] [ Designated as safety issue: No ]
    Cmax (Cycle 1) and Cmax at steady state (Cmax,ss, Cycle 4) of ramucirumab are provided.

  • Area Under the Curve (AUC) of Ramucirumab [ Time Frame: Day 1 of Cycles 1 and 4 (cycle=21 days) ] [ Designated as safety issue: No ]
    AUC from time zero to infinity (AUC[0-inf], Cycle 1) and at steady state (AUC tau, Cycle 4) of ramucirumab are provided.

  • Half Life (t 1/2) of Ramucirumab [ Time Frame: Day 1 of Cycles 1 and 4 (cycle=21 days) ] [ Designated as safety issue: No ]
  • Clearance (Cl) of Ramucirumab [ Time Frame: Day 1 of Cycle 1 and Cycle 4 (cycle=21 days) ] [ Designated as safety issue: No ]
    Clearance (Cycle 1) and at steady state (Clss, Cycle 4) of ramucirumab are provided.

  • Steady State Volume of Distribution (Vss) of Ramucirumab [ Time Frame: Day 1 of Cycle 1 and 4 (cycle=21 days) ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: December 2010
Study Completion Date: February 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ramucirumab and docetaxel combination Biological: Ramucirumab
Ramucirumab administered as an intravenous (I.V.) infusion at a dose of 10 milligrams per kilogram (mg/kg) every 3 weeks.
Other Names:
  • IMC-1121B
  • LY3009806
Drug: Docetaxel
Docetaxel administered by intravenous (I.V.) infusion at a dose of 75 milligrams per square meter (mg/m^2) every 3 weeks.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The participant is Japanese
  • The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • The participant has a histopathologically or cytologically confirmed diagnosis of breast adenocarcinoma that is now metastatic or locally-recurrent and inoperable with curative intent
  • The participant has measurable and/or non-measurable disease
  • The participants' primary and/or metastatic tumor is Human Epidermal Growth Factor Receptor 2 (HER2) negative
  • The participant received neo adjuvant or adjuvant taxane therapy ≥ 6 months prior to the study
  • The participant received neo adjuvant or adjuvant biologic therapy ≥ 6 weeks prior to the study
  • The participant completed all prior radiotherapy ≥ 3 weeks prior to the study registration date
  • The participant received prior hormonal therapy for breast cancer in the neo adjuvant, adjuvant,and/or the metastatic setting ≥ 2 weeks prior to the study registration date
  • The participant's left ventricular ejection fraction (LVEF) is within normal ranges
  • The participant has adequate hematologic, hepatic, and coagulation function.
  • Eligible participants of reproductive potential agree to use adequate contraceptive methods (hormonal or barrier methods) during the study period and for 12 weeks after the last dose of study medication

Exclusion Criteria:

  • The 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. Participants with previous treatment of malignancy is eligible, provided that she has been disease free for >3 years
  • The participant has a known sensitivity to docetaxel
  • The participant has a known sensitivity to agents of similar biologic composition as ramucirumab
  • The participant has a history of chronic diarrheal disease within 6 months prior to the study registration date
  • The participant has received irradiation to a major bone marrow area within 30 days prior to the study registration date
  • The participant has received any experimental agents within 4 weeks prior to the study registration date
  • The participant has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
  • The participant has Grade 3-4 bleeding within 3 months prior to the study registration date
  • The participant has an ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy
  • The participant has uncontrolled hypertension, symptomatic congestive heart failure, psychiatric illness, or any other serious uncontrolled medical disorders
  • The participant has brain metastases
  • The participant has known human immunodeficiency virus infection or acquired immunodeficiency syndrome related illness
  • The participant is pregnant or lactating
  • The participant has not fully recovered from effects of prior chemotherapy
  • The participant has undergone major surgery within 28 days prior to the study registration date
  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: NCT01256567

Locations
Japan
ImClone Investigational Site
Hidaka, Japan, 350-1298
ImClone Investigational Site
Matsuyama, Japan, 790-0007
Imclone Investigational Site
Nagoya, Japan, 464-8681
ImClone Investigational Site
Osaka, Japan, 540-0006
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: NCT01256567     History of Changes
Other Study ID Numbers: 14200, CP12-1028, I4T-IE-JVBX
Study First Received: December 7, 2010
Results First Received: May 16, 2014
Last Updated: May 16, 2014
Health Authority: Japan: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Docetaxel
Antimitotic Agents
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 20, 2014