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

NCT ID: NCT00364611

Last Updated: 2012-08-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2012-04-30

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.

Detailed Description

The study included:

• Study registration on Day 1: Treatment Cycle 1 was initiated within 14 days of signing informed consent
• Treatment was administered in 3 week treatment cycles until the participant developed unacceptable toxicity, had disease progression, withdrew consent, or died
• If participants experienced a complete response (CR), partial response (PR), or stable disease (SD) at Cycle 8 or beyond or had unacceptable toxicity due to docetaxel, they could continue on bevacizumab and/or trastuzumab until they developed unacceptable toxicity, had disease progression, or withdrew consent
• Participants had follow-up assessments within 30 days after discontinuation of treatment with the last of the study drugs for any reason other than death

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Docetaxel and Bevacizumab

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

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: 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

Docetaxel

Intervention Type: DRUG

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

Docetaxel, Bevacizumab and Trastuzumab

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

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: 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

Docetaxel

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: 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

Interventions

Bevacizumab

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

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Trastuzumab

• 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

Intervention Type: DRUG

Other Intervention Names

Avastin; Herceptin

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically proven adenocarcinoma of the breast at first diagnosis

2. Stage IV disease with at least one measurable lesion according to the RECIST criteria

3. HER2/neu positive as determined by 3+ immunohistochemistry (IHC) staining or fluorescence in situ hybridization (FISH) positivity or negative tumors

4. Life expectancy of >/= 24 weeks

5. No prior chemotherapy for metastatic breast cancer. (Prior endocrine therapy is permitted).

6. 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)

7. At least 4 weeks since prior surgery, radiotherapy, endocrine therapy, or experimental drug therapy with complete recovery from the effects of these interventions

8. 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

9. 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.

10. 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

Exclusion Criteria

1. Prior chemotherapy for metastatic breast cancer

2. Prior treatment with bevacizumab or other anti-VEGF therapy

3. 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

4. Current or prior history of brain or leptomeningeal metastases

5. Presence of neuropathy >/= 2

6. Presence of any non-healing wound, fracture, or ulcer, or the presence of clinically significant (>/= Grade 2) peripheral vascular disease

7. 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

8. Clinically significant cardiovascular disease

9. 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

10. History of bleeding diathesis or coagulopathy

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Barry Childs, MD

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Countries

United States

Other Identifiers

DOCET_L_00712

Identifier Type: -

Identifier Source: org_study_id