A Phase II, Open-Label, Multicenter, Pilot Study of the Safety & Efficacy of Two Docetaxel-Based Regimens Plus Bevacizumab for the Adjuvant Treatment of Subjects With Node Positive or High Risk Node Negative Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Docetaxel
- Conditions
- Breast Neoplasms
- Sponsor
- Sanofi
- Enrollment
- 127
- Locations
- 1
- Primary Endpoint
- Percent of Participants With Grade 3/4 Clinical Congestive Heart Failure (CHF)
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
This is a phase II, open-label, multicenter, pilot study of the safety and efficacy of two Docetaxel-based regimens plus bevacizumab for the adjuvant treatment of participants with node positive or high risk node negative breast cancer.
The primary objective of this study was to evaluate the cardiac safety, and the secondary objectives were to evaluate safety and toxicity of participants treated with bevacizumab ± trastuzumab administered with 2 different docetaxel-based combination regimens.
This study was originally designed to also evaluate disease-free survival (DFS) and overall survival (OS); however, based on a protocol amendment, follow-up was shortened from 10 years to 2 years, and the efficacy endpoints of disease free survival and overall survival were deleted from the protocol.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants who met the following criteria were eligible for this study:
- •Woman aged 18 to 70 years, inclusive
- •Had histologically proven breast cancer with the most recent surgery done for breast cancer up to 60 days prior to study registration
- •Had definitive surgical treatment - either mastectomy, or breast conserving surgery with axillary lymph node dissection (or sentinel lymph node biopsy) for operable breast cancer (T1-3, clinical N0-1, and M0)
- •Must have been either "lymph node positive" or "high risk lymph node negative"
- •Were lymph node positive participants who had at least 1 axillary lymph node involved by breast cancer. (with lymph node metastasis \>0.2 mm)
- •Were high risk lymph node negative participants had no lymph node involvement and at least 1 of the following factors:
- •tumor size \>2 cm
- •estrogen receptor (ER) and progesterone receptor (PR) status negative
- •histologic and/or nuclear Grade 2/3
Exclusion Criteria
- •Participants with the following criteria were excluded from this study:
- •Had prior systemic anticancer therapy for invasive breast cancer (immunotherapy,hormonotherapy, chemotherapy)
- •Had prior anthracycline therapy, taxoids, or platinum salts for any malignancy
- •Had prior radiation therapy for breast cancer or any radiotherapy to the chest wall for any other malignancy
- •Was pregnant or lactating
- •Had pre-existing motor or sensory neurotoxicity of a severity \>Grade 2 by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 3.0
- •Had cardiac disease or risk for same as follows:
- •Any documented myocardial infarction
- •Angina pectoris that required the use of anti-anginal medication
- •Any history of documented congestive heart failure
Arms & Interventions
Stratum 1: TAC + Bevacizumab
Human epidermal growth factor receptor-2 (HER2) negative participants stratified at registration, were administered chemotherapy with docetaxel, doxorubicin and cyclosphosphamide (TAC) + bevacizumab for Cycles 1-6 (every 3 weeks), and followed with maintenance therapy with bevacizumab every 3 weeks for a total of 52 weeks. All participants were administered prophylactic recombinant Granulocyte Colony Stimulating Factor (G-CSF) during chemotherapy, based on a dose recommended by the manufacturer. For participants with estrogen receptor (ER) or progesterone receptor (PR) positive tumors, anti-estrogen therapy was recommended. Participants could receive radiation therapy at the discretion of the treating medical and radiation oncologist.
Intervention: Docetaxel
Stratum 1: TAC + Bevacizumab
Human epidermal growth factor receptor-2 (HER2) negative participants stratified at registration, were administered chemotherapy with docetaxel, doxorubicin and cyclosphosphamide (TAC) + bevacizumab for Cycles 1-6 (every 3 weeks), and followed with maintenance therapy with bevacizumab every 3 weeks for a total of 52 weeks. All participants were administered prophylactic recombinant Granulocyte Colony Stimulating Factor (G-CSF) during chemotherapy, based on a dose recommended by the manufacturer. For participants with estrogen receptor (ER) or progesterone receptor (PR) positive tumors, anti-estrogen therapy was recommended. Participants could receive radiation therapy at the discretion of the treating medical and radiation oncologist.
Intervention: Doxorubicin
Stratum 1: TAC + Bevacizumab
Human epidermal growth factor receptor-2 (HER2) negative participants stratified at registration, were administered chemotherapy with docetaxel, doxorubicin and cyclosphosphamide (TAC) + bevacizumab for Cycles 1-6 (every 3 weeks), and followed with maintenance therapy with bevacizumab every 3 weeks for a total of 52 weeks. All participants were administered prophylactic recombinant Granulocyte Colony Stimulating Factor (G-CSF) during chemotherapy, based on a dose recommended by the manufacturer. For participants with estrogen receptor (ER) or progesterone receptor (PR) positive tumors, anti-estrogen therapy was recommended. Participants could receive radiation therapy at the discretion of the treating medical and radiation oncologist.
Intervention: Cyclophosphamide
Stratum 1: TAC + Bevacizumab
Human epidermal growth factor receptor-2 (HER2) negative participants stratified at registration, were administered chemotherapy with docetaxel, doxorubicin and cyclosphosphamide (TAC) + bevacizumab for Cycles 1-6 (every 3 weeks), and followed with maintenance therapy with bevacizumab every 3 weeks for a total of 52 weeks. All participants were administered prophylactic recombinant Granulocyte Colony Stimulating Factor (G-CSF) during chemotherapy, based on a dose recommended by the manufacturer. For participants with estrogen receptor (ER) or progesterone receptor (PR) positive tumors, anti-estrogen therapy was recommended. Participants could receive radiation therapy at the discretion of the treating medical and radiation oncologist.
Intervention: Bevacizumab
Stratum 2: TCH + Bevacizumab
HER2 positive participants stratified at registration, were administered chemotherapy with docetaxel, carboplatin and trastuzumab (TCH) + bevacizumab for Cycles 1-6 (every 3 weeks), and followed with maintenance therapy with bevacizumab and trastuzumab every 3 weeks for a total of 52 weeks. All participants were administered prophylactic recombinant Granulocyte Colony Stimulating Factor (G-CSF) during chemotherapy, based on a dose recommended by the manufacturer. For participants with estrogen receptor (ER) or progesterone receptor (PR) positive tumors, anti-estrogen therapy was recommended. Participants could receive radiation therapy at the discretion of the treating medical and radiation oncologist.
Intervention: Docetaxel
Stratum 2: TCH + Bevacizumab
HER2 positive participants stratified at registration, were administered chemotherapy with docetaxel, carboplatin and trastuzumab (TCH) + bevacizumab for Cycles 1-6 (every 3 weeks), and followed with maintenance therapy with bevacizumab and trastuzumab every 3 weeks for a total of 52 weeks. All participants were administered prophylactic recombinant Granulocyte Colony Stimulating Factor (G-CSF) during chemotherapy, based on a dose recommended by the manufacturer. For participants with estrogen receptor (ER) or progesterone receptor (PR) positive tumors, anti-estrogen therapy was recommended. Participants could receive radiation therapy at the discretion of the treating medical and radiation oncologist.
Intervention: Carboplatin
Stratum 2: TCH + Bevacizumab
HER2 positive participants stratified at registration, were administered chemotherapy with docetaxel, carboplatin and trastuzumab (TCH) + bevacizumab for Cycles 1-6 (every 3 weeks), and followed with maintenance therapy with bevacizumab and trastuzumab every 3 weeks for a total of 52 weeks. All participants were administered prophylactic recombinant Granulocyte Colony Stimulating Factor (G-CSF) during chemotherapy, based on a dose recommended by the manufacturer. For participants with estrogen receptor (ER) or progesterone receptor (PR) positive tumors, anti-estrogen therapy was recommended. Participants could receive radiation therapy at the discretion of the treating medical and radiation oncologist.
Intervention: Trastuzumab
Stratum 2: TCH + Bevacizumab
HER2 positive participants stratified at registration, were administered chemotherapy with docetaxel, carboplatin and trastuzumab (TCH) + bevacizumab for Cycles 1-6 (every 3 weeks), and followed with maintenance therapy with bevacizumab and trastuzumab every 3 weeks for a total of 52 weeks. All participants were administered prophylactic recombinant Granulocyte Colony Stimulating Factor (G-CSF) during chemotherapy, based on a dose recommended by the manufacturer. For participants with estrogen receptor (ER) or progesterone receptor (PR) positive tumors, anti-estrogen therapy was recommended. Participants could receive radiation therapy at the discretion of the treating medical and radiation oncologist.
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Percent of Participants With Grade 3/4 Clinical Congestive Heart Failure (CHF)
Time Frame: up to 2 years
The percentage of participants with Grade 3/4 clinical CHF was calculated. Grade 3/4 CHF symptoms included cardiac failure congestive, cardiomyopathy, and left ventricular dysfunction (LVEF). Echocardiography (ECG) or multiple-gated acquisition (MUGA) scans were scheduled after Cycles 3 and 6 of chemotherapy, after every 3rd cycle of trastuzumab alone, at end of therapy and every 6 months at follow-up to measure changes in LVEF. Clinical symptoms e.g., shortness of breath, tachycardia, cough, neck vein distention, cardiomegaly, hepatomegaly were further investigated for CHF.
Secondary Outcomes
- Disease-free Survival (DFS) & Overall Survival (OS) of Participants(up to 10 years)