Pilot Study of Docetaxel & Bevacizumab +/- Trastuzumab in First-Line Treatment of Patients With Metastatic Breast Cancer

NCT00364611 | Completed Phase 2 Results

• 1 other identifier: DOCET_L_00712
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

Pilot, phase II, parallel-group, open-label, noncomparative, prospective, multicenter study designed to evaluate the progression-free survival of docetaxel and bevacizumab ± trastuzumab for the first-line treatment of participants with metastatic breast cancer. Participants were stratified according to human epidermal growth factor receptor-2 (HER2) status at the time of enrollment. HER2 negative participants were assigned to receive docetaxel and bevacizumab (DB). HER2 positive participants were assigned to receive docetaxel, bevacizumab, and trastuzumab (DBT). All participants (except one) were off study treatment on 30 June 2011. All efficacy analysis and safety analysis was performed using the cut-off date of June 2011. One participant continued treatment till 11 March 2012. For this participant, adverse events were collected upto 19 April 2012 and included in the safety analysis.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) Rate: Percentage of Participants With PFS

  PFS was the time from registration to first documentation of * progressive disease (PD) based on Response Evaluation Criteria in Solid Tumors (RECIST) - criteria pre-defining changes in lesion size or appearance * symptomatic deterioration * death due to any cause (in absence of PD). The Percentage of participants with PFS is reported. For the analysis, participants were censored * on the last available tumor assessment date on study treatment if they * had no PFS event * were on anticancer therapy not related to study treatment * on the registration date if they * did not receive study drug * had no post baseline tumor assessment

  Up to 6 months and 12 months after treatment initiation

• Time to Progression-free Survival (PFS)

  Time to PFS was the interval from the date of registration to the earliest of the following documented dates: * PD as defined by RECIST (criteria pre-defining changes in lesion size or appearance) * symptomatic deterioration * death. Time to PFS was estimated from Kaplan-Meier Plots.

  From treatment initiation to PFS event (up to June 2011)

Secondary Outcomes (5)

• Confirmed Overall Response (OR) Based on RECIST Criteria

  From treatment initiation to June 2011

• Number of Participants With Confirmed Clinical Benefit Based on RECIST Criteria

  From treatment initiation to June 2011

• Duration of Response (DR)

  From treatment initiation to June 2011

• Overall Survival (OS) Time

  From treatment initiation to June 2011

• Number of Participants With Adverse Events (AE)

  From treatment initiation to 30 days after the last dose of study treatment

Study Arms (2)

Docetaxel and Bevacizumab

EXPERIMENTAL

Stratum 1: HER2 Negative participants with metastatic breast cancer treated with DB (docetaxel and bevacizumab) intravenously (IV) every 3 weeks (q3w) until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met

Drug: Bevacizumab; Drug: Docetaxel

Docetaxel, Bevacizumab and Trastuzumab

EXPERIMENTAL

Stratum 2: HER2 Positive participants with metastatic breast cancer treated with DBT (docetaxel, bevacizumab, and trastuzumab) IV q3w until treatment discontinuation criteria (unacceptable toxicity, disease progression or death) are met

Drug: Bevacizumab; Drug: Docetaxel; Drug: Trastuzumab

Interventions

Bevacizumab DRUG

Bevacizumab (Avastin) 15 mg/kg will be administered prior to chemotherapy on * On Day 1 of the 1st cycle over 120 minutes * On Day 1 of the 2nd cycle over 90 minutes, if no reaction on the first dose * On Day 1 of 3rd cycle over 60 minutes, if no reaction on previous doses * On Day 1 of subsequent cycles over 30 minutes, if no reaction on previous doses

Also known as: Avastin

Docetaxel and Bevacizumab; Docetaxel, Bevacizumab and Trastuzumab

Docetaxel DRUG

Docetaxel 75 mg/m\^2 IV infused over 60 minutes after completion of Bevacizumab infusion q3w

Docetaxel and Bevacizumab; Docetaxel, Bevacizumab and Trastuzumab

Trastuzumab DRUG

* A loading dose of 8 mg/kg Trastuzumab (Herceptin) IV will be infused over 90 minutes on Day 2 of Cycle 1. * For all subsequent cycles 6 mg/kg trastuzumab will be administered on Day 1 one hour following completion of docetaxel infusion

Also known as: Herceptin

Docetaxel, Bevacizumab and Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven adenocarcinoma of the breast at first diagnosis
• Stage IV disease with at least one measurable lesion according to the RECIST criteria
• HER2/neu positive as determined by 3+ immunohistochemistry (IHC) staining or fluorescence in situ hybridization (FISH) positivity or negative tumors
• Life expectancy of \>/= 24 weeks
• No prior chemotherapy for metastatic breast cancer. (Prior endocrine therapy is permitted).
• Prior neoadjuvant or adjuvant chemotherapy is permitted, or at least 12 months must have elapsed since the neoadjuvant or adjuvant therapy. Subjects may have received prior adjuvant anthracyclines (maximum cumulative dose, 360 mg/m\^2 doxorubicin or 750 mg/m\^2 epirubicin)
• At least 4 weeks since prior surgery, radiotherapy, endocrine therapy, or experimental drug therapy with complete recovery from the effects of these interventions
• It is recommended that all baseline staging should be completed within 35 days prior to study entry. All subjects will have the following workup as applicable; CT scan of brain, CT scan or MRI of chest and abdomen, and bone scan or PET scan. In cases of positive bone or PET scans, bone X-ray evaluation and/or MRI is required to confirm or exclude metastatic bone disease. Subjects with metastatic disease limited to bone are ineligible unless at least one lytic lesion is measurable and can be followed by RECIST criteria. Other tests may be performed as clinically indicated
• Normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF) of \>/= 50% or shortening fraction (multiple-gated acquisition \[MUGA\] scan or echocardiography respectively). The result must be greater than the lower limit of normal (LLN) for the institution.
• Subjects receiving bisphosphonate therapy; however, if bisphosphonates were started within \<2 months prior to treatment the bone lesions will not be evaluated for response, and the subjects must have another site of metastatic disease that is either measurable or evaluable for response

You may not qualify if:

• Prior chemotherapy for metastatic breast cancer
• Prior treatment with bevacizumab or other anti-VEGF therapy
• Concurrent treatment with any other non-protocol anticancer therapy with the exception of radiation therapy as long as all target lesions being followed are not in the radiation field and if HER2/neu positive, HER2/neu-directed therapy
• Current or prior history of brain or leptomeningeal metastases
• Presence of neuropathy \>/= 2
• Presence of any non-healing wound, fracture, or ulcer, or the presence of clinically significant (\>/= Grade 2) peripheral vascular disease
• History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma in-situ of the cervix
• Clinically significant cardiovascular disease
• Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning therapy
• History of bleeding diathesis or coagulopathy

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Docetaxel; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi-aventis

Contact-us@sanofi.com

Study Officials

• Barry Childs, MD

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2006
• First Posted: August 15, 2006
• Study Start: August 1, 2006
• Primary Completion: June 1, 2011
• Study Completion: April 1, 2012
• Last Updated: August 23, 2012
• Results First Posted: August 23, 2012

Record last verified: 2012-04

Locations

US (1)