Clinical trial NCT00364611: Pilot Study of Docetaxel & Bevacizumab +/- Trastuzumab in First-Line Treatment of Patients With Metastatic Breast Cancer
Official title: A Pilot, Phase II, Multicenter, Open-Label, Prospective Evaluation of Docetaxel and Bevacizumab ± Trastuzumab in the First-Line Treatment of Patients With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-08-15
Enrollment: 73
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: The following information on clinical trials is provided for information purposes only to allow participants and physicians to have an initial discussion about the trial. This information is not intended to be complete information about the trial, to contain all considerations that may be relevant to potential participation in the trial, or to replace the advice of a personal physician or health professional.

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

Primary outcomes:
measure: Progression-free Survival (PFS) Rate: Percentage of Participants With PFS
timeFrame: Up to 6 months and 12 months after treatment initiation
measure: Time to Progression-free Survival (PFS)
timeFrame: From treatment initiation to PFS event (up to June 2011)
Secondary outcomes:
measure: Confirmed Overall Response (OR) Based on RECIST Criteria
timeFrame: From treatment initiation to June 2011
measure: Number of Participants With Confirmed Clinical Benefit Based on RECIST Criteria
timeFrame: From treatment initiation to June 2011
measure: Duration of Response (DR)
timeFrame: From treatment initiation to June 2011
measure: Overall Survival (OS) Time
timeFrame: From treatment initiation to June 2011
measure: Number of Participants With Adverse Events (AE)
timeFrame: From treatment initiation to 30 days after the last dose of study treatment
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
Study officials:
affiliation: Sanofi
name: Barry Childs, MD
role: STUDY_DIRECTOR
References: