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

Phase 1

Completed

• Conditions: Breast Cancer; Metastatic Breast Cancer
• Interventions: Biological: Ramucirumab; Drug: Docetaxel

• Registration Number: NCT01256567
• Lead Sponsor: Eli Lilly and Company

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-12
• Study First Submitted: 2010-12-07
• Study First Submitted QC: 2010-12-07
• Study First Posted: 2010-12-08
• Primary Completion: 2012-11
• Study Completion: 2013-02
• Status Verified: 2014-05
• Results First Submitted: 2014-05-16
• Results First Submitted QC: 2014-05-16
• Last Update Submitted: 2014-05-16
• Results First Posted: 2014-06-18
• Last Update Posted: 2014-06-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 7

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ramucirumab and docetaxel combination	Ramucirumab	-
ramucirumab and docetaxel combination	Docetaxel	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	Baseline up to data cut off (approximately 48.3 weeks)	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

Name	Time	Method
Serum Anti-IMC-1121B Antibody Assessment (Immunogenicity)	Baseline up to data cut off (approximately 48.3 weeks)	The number of participants with a positive anti-IMC-1121B titer at any point during the study.
Maximum Concentration (Cmax) of Ramucirumab	Day 1 of Cycle 1 and Cycle 4 (cycle=21 days)	Cmax (Cycle 1) and Cmax at steady state (Cmax,ss, Cycle 4) of ramucirumab are provided.
Area Under the Curve (AUC) of Ramucirumab	Day 1 of Cycles 1 and 4 (cycle=21 days)	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	Day 1 of Cycles 1 and 4 (cycle=21 days)
Clearance (Cl) of Ramucirumab	Day 1 of Cycle 1 and Cycle 4 (cycle=21 days)	Clearance (Cycle 1) and at steady state (Clss, Cycle 4) of ramucirumab are provided.
Steady State Volume of Distribution (Vss) of Ramucirumab	Day 1 of Cycle 1 and 4 (cycle=21 days)

Trial Locations

Locations (2)

ImClone Investigational Site; 🇯🇵 Osaka, Japan

Imclone Investigational Site; 🇯🇵 Nagoya, Japan