A Study of Bevacizumab in Combination With Gemcitabine and Carboplatin in Participants With Triple Negative Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01201265
First received: September 6, 2010
Last updated: April 21, 2016
Last verified: April 2016
  Purpose
This multicenter study will assess the efficacy and safety of bevacizumab in combination with gemcitabine and cisplatin as first line treatment in participants with triple negative metastatic breast cancer. Participants will receive bevacizumab at a dose of 15 mg/kg intravenously (iv) every 3 weeks, plus gemcitabine (1000 mg/m2 iv) and carboplatin (iv to an area under curve [AUC]=2) on Days 1 and 8 of each 3-week cycle. Anticipated time on study treatment is until disease progression.

Condition Intervention Phase
Breast Cancer
Drug: Bevacizumab
Drug: Carboplatin
Drug: Gemcitabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi Centre, Pilot Phase II Trial Assessing the Efficacy and Safety of Bevacizumab + Gemcitabine + Carboplatin as First Line Treatment for Patients Diagnosed With Triple Negative Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: From the date of registration until the disease progression or death (up to 1541 days). ] [ Designated as safety issue: No ]
    Progression free survival (PFS) was calculated in days from the date of registration until the earliest date of documented disease progression or death. The median PFS time with 95% confidence interval (CI) was estimated using Kaplan Meier method. The progression-free survival was assessed utilizing computer tomography (CT)/ magnetic resonance imaging (MRI)/bone scans and X-ray and Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.


Secondary Outcome Measures:
  • Percentage of Participants Achieving an Overall Response [ Time Frame: From the date of registration until the disease progression or death (up to 1541 days) ] [ Designated as safety issue: No ]
    The overall response rate (ORR) was defined as complete response (CR) + partial response (PR). ORR was summarized using number and percentage along with two-sided 95% Pearson-Clopper CI. The overall response rate was assessed utilizing the RECIST v. 1.1. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 millimeter (mm). PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters.

  • Percentage of Participants Achieving a Clinical Benefit Response (CBR) [ Time Frame: From the date of registration until the disease progression or death (up to 1541 days) ] [ Designated as safety issue: No ]
    Clinical benefit response was defined as a complete response (CR), partial response (PR) or stable disease (SD). CBR was assessed using Recist v.1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

  • Time to Progression (TTP) [ Time Frame: From the date of registration until the disease progression (up to 1541 days). ] [ Designated as safety issue: No ]
    Duration of time to progression (TTP) was estimated using the Kaplan-Meier method. The time to progression was calculated in days from the date of registration until the earliest date of documented disease progression.

  • Overall Survival (OS) [ Time Frame: From the date of registration until the disease progression or death (up to 1541 days) ] [ Designated as safety issue: No ]
    Overall survival was measured from the date of the first study drug dose to the date of death from any cause. The median overall survival time with 95%CI was estimated using Kaplan-Meier method.

  • Number of Participants With an Adverse Event (AE) [ Time Frame: Up to 28 days after termination of study treatment (approximately 1569 days) ] [ Designated as safety issue: No ]
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  • Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) [ Time Frame: Baseline, cycle 6 ] [ Designated as safety issue: No ]
    The EORTC QLQ-C30 (version 3.0) questionnaire incorporates 9 multi scale items: 5 functional scales (physical, role, cognitive, emotional and social); 3 symptom scales (fatigue, pain and nausea & vomiting); and a global health and quality-of-life scale. It contains 30 questions. The score for each item and the overall score ranges from 0 to 100. A high overall scale and subscale scores represent improved health status. However, in case of symptoms, higher scores suggest increased perception of these symptoms.

  • Change From Baseline in Systolic Blood Pressure (SBP) [ Time Frame: Baseline, Cycle 6, 12 of treatment ] [ Designated as safety issue: No ]
    Change from baseline in SBP was analyzed by overall response (CR+PR, SD+PD).

  • Change From Baseline in Diastolic Blood Pressure (DBP) [ Time Frame: Baseline, Cycle 6, 12 of treatment ] [ Designated as safety issue: No ]
    Change from baseline in DBP was analyzed by overall response (CR+PR, SD+PD).


Enrollment: 40
Study Start Date: February 2011
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Overall Participants
Participants received a combination therapy of bevacizumab with gemcitabine plus carboplatin.
Drug: Bevacizumab
15 mg/kg iv every 3 weeks
Other Name: Avastin
Drug: Carboplatin
to an AUC = 2, on days 1 and 8 of each 3-week cycle
Drug: Gemcitabine
1000 mg/m2 iv on days 1 and 8 of each 3-week cycle

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female participants, >/= 18 years of age
  • Metastatic breast cancer
  • Estrogen receptor-, progesterone- and human epidermal growth factor receptor 2 (HER2)-negative disease
  • Treatment-naïve for metastatic breast cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Adequate hematological, renal and liver function
  • Patients should have received Anthracyclines and Taxanes in the adjuvant setting
  • Women of childbearing potential must agree to use adequate contraception (per institutional standard of care) during treatment and until 6 months after the last administration of investigational products

Exclusion Criteria:

  • Prior first line treatment for metastatic breast cancer
  • Central nervous system (CNS) metastasis
  • Uncontrolled hypertension (> 170/95 mmHg)
  • Evidence of bleeding diathesis, coagulopathy or hemorrhage at baseline
  • Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
  • Prior therapy with gemcitabine or carboplatin in the metastatic setting. Participants having received gemcitabine or carboplatin as part of adjuvant therapy are eligible, if recurrence was first documented >6 months after the last exposure to the drug(s)
  • Requirement of chronic use of immunosuppressive agents
  • HIV, hepatitis B or hepatitis C infection
  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: NCT01201265

Locations
India
Ahmedabad, India, 380009
Bangalore, India, 560029
Bangalore, India, 560054
Delhi, India, 110029
Gandhinagar, India, 382428
Mumbai, India, 400012
Mumbai, India, 400016
Mumbai, India, 400020
New Delhi, India, 110011
New Delhi, India, 110085
Pune, India, 411004
Vellore, India, 632004
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01201265     History of Changes
Other Study ID Numbers: ML25420 
Study First Received: September 6, 2010
Results First Received: April 21, 2016
Last Updated: April 21, 2016
Health Authority: India: Ministry of Health

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Gemcitabine
Bevacizumab
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on August 30, 2016