Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab With or Without Trastuzumab for Adjuvant Treatment of Patients With Breast Cancer

NCT ID: NCT00365365

Last Updated: 2012-09-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2011-10-31

Brief Summary

This is a phase IIb, randomized, parallel-group, noncomparative, multicenter, pilot study designed to evaluate the safety and efficacy of bevacizumab with or without (+/-) trastuzumab administered with three different docetaxel-based combination regimens for the adjuvant treatment of participants with node positive or high-risk node negative breast cancer.

Detailed Description

In this study, participants were stratified according to HER2 status at the time of enrollment. HER2-negative participants were randomized in a 1:1 ratio to either stratum 1 (AC->T sequential + bevacizumab) or stratum 2 (TAC + bevacizumab). All HER2-positive participants were assigned to stratum 3 (TCH + bevacizumab).

The study included a treatment period of 1 year, followed by a 2 year posttreatment survival follow-up period.

Conditions

Breast Cancer

Study Design

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

Study Groups

Stratum 1 (AC->T + bevacizumab)

HER2-negative participants administered

• doxorubicin and cyclophosphamide (AC) + bevacizumab for 4 cycles followed by
• docetaxel (T) + bevacizumab for 4 cycles followed by
• bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed

Group Type: EXPERIMENTAL

Doxorubicin and cyclophosphamide (AC) + bevacizumab

Intervention Type: DRUG

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• doxorubicin 60 mg/m^2 IV push or infusion followed by cyclophosphamide 600 mg/m^2 IV push or infusion
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

Docetaxel (T) + bevacizumab

Intervention Type: DRUG

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• docetaxel 100 mg/m^2 IV
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

Note: The starting dose of docetaxel was reduced to 75 mg/m^2 if toxicity occurred that met the criteria for doxorubicin dose reduction

Bevacizumab maintenance therapy

Intervention Type: DRUG

• bevacizumab 15 mg/kg was infused IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

Stratum 2 (TAC + bevacizumab)

HER2-negative participants administered

• docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab for 6 cycles followed by
• bevacizumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed

Group Type: EXPERIMENTAL

Docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab

Intervention Type: DRUG

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• doxorubicin 50 mg/m^2 IV push or infusion followed by cyclophosphamide 500 mg/m^2 IV push or infusion followed by docetaxel 75 mg/m^2
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

Bevacizumab maintenance therapy

Intervention Type: DRUG

• bevacizumab 15 mg/kg was infused IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

Stratum 3 (TCH + bevacizumab)

All HER2-positive participants administered

• docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab for 6 cycles followed by
• bevacizumab and trastuzumab maintenance therapy for total of 52 weeks from date of first dose regardless of number of doses received or missed

Group Type: EXPERIMENTAL

Docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab

Intervention Type: DRUG

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• docetaxel in 75 mg/m^2 IV followed by carboplatin AUC 6 mg/mL/min IV followed by
• trastuzumab 6 mg/kg by IV infusion (For the first cycle 1 only a loading dose of trastuzumab 8 mg/kg IV was infused on Day 2)
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

Bevacizumab and trastuzumab maintenance therapy

Intervention Type: DRUG

• bevacizumab 15 mg/kg was infused IV followed by
• trastuzumab 6 mg/kg IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

Interventions

Doxorubicin and cyclophosphamide (AC) + bevacizumab

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• doxorubicin 60 mg/m^2 IV push or infusion followed by cyclophosphamide 600 mg/m^2 IV push or infusion
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

Intervention Type: DRUG

Docetaxel (T) + bevacizumab

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• docetaxel 100 mg/m^2 IV
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

Note: The starting dose of docetaxel was reduced to 75 mg/m^2 if toxicity occurred that met the criteria for doxorubicin dose reduction

Intervention Type: DRUG

Docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• doxorubicin 50 mg/m^2 IV push or infusion followed by cyclophosphamide 500 mg/m^2 IV push or infusion followed by docetaxel 75 mg/m^2
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

Intervention Type: DRUG

Docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab

For every 3-week cycle

• bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
• docetaxel in 75 mg/m^2 IV followed by carboplatin AUC 6 mg/mL/min IV followed by
• trastuzumab 6 mg/kg by IV infusion (For the first cycle 1 only a loading dose of trastuzumab 8 mg/kg IV was infused on Day 2)
• Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy

Intervention Type: DRUG

Bevacizumab and trastuzumab maintenance therapy

• bevacizumab 15 mg/kg was infused IV followed by
• trastuzumab 6 mg/kg IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

Intervention Type: DRUG

Bevacizumab maintenance therapy

• bevacizumab 15 mg/kg was infused IV

Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.

Intervention Type: DRUG

Other Intervention Names

Avastin® (bevacizumab); Adriamycin® (doxorubicin); Taxotere® (docetaxel); Avastin® (bevacizumab); Taxotere® (docetaxel); Avastin® (bevacizumab); Taxotere® (docetaxel); Herceptin® (trastuzumab); Avastin® (bevacizumab); Avastin® (bevacizumab); Herceptin® (trastuzumab); Avastin® (bevacizumab)

Eligibility Criteria

Inclusion Criteria

• Women >/= 18 years of age.
• Histologically proven breast cancer with an interval between definitive breast surgery that includes axillary lymph node (LN) dissection or axillary nodal evaluation and study registration of < 60 days. (Note: Cycle 1 of chemotherapy treatment may NOT be infused until > 28 days after the date of definitive breast surgery and the participant must be recovered from any clinically significant toxicity thereof.)
• Definitive surgical treatment must be either mastectomy, or breast conserving surgery with axillary lymph node dissection (axillary lymph node evaluation can be either full axillary node dissection or sentinel LN evaluation followed by dissection if sentinel LN is positive) for operable breast cancer (pT1-4 [including inflammatory], pNO-3, and MO). Margins of resected specimen from definitive surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma in-situ (DCIS). Lobular carcinoma in-situ does not count as a positive margin.
• Subjects must be either lymph node-positive (pN1-3) or lymph node-negative (pN0) with high-risk features as determined by Investigator.
• High-risk, lymph node-negative participants, (pN0) will be defined as subjects having invasive adenocarcinoma with either a negative sentinel node biopsy (pN0[sn]) OR negative lymph node dissection (pN0) disease AND tumor size > 2 cm or tumor size >/= 1 cm with at least one of the following factors:

• negative estrogen receptor (ER) and negative progesterone receptor (PR) status
• histologic and/or nuclear Grade 2-3; or
• age < 35 years
• HER2/neu positive or negative tumors are eligible. HER2 positivity must be documented by fluorescence in situ hybridization (FISH).
• Estrogen and progesterone receptor status must be performed on the primary tumor prior to study entry. Results must be pending or known at the time of study entry.
• Normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF) 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.
• Hematology evaluation within 2 weeks prior to study entry:

• Absolute neutrophil count (ANC) >/= 1,500/μL
• Platelets >/= 100,000/μL
• Hemoglobin >/= 9 g/dL
• Hepatic function evaluation within 2 weeks prior to study entry:

• Total bilirubin </= ULN for the institution
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be in the acceptable range.
• Complete staging work-up as follows: All subjects must have an appropriate radiographic evaluation, e.g., computed tomography (CT), positron emission tomography (PET)/CT, and/or (magnetic resonance imaging) MRI of the brain, chest, abdomen and pelvis, and imaging of bone by either a bone scan or PET scan. In cases of positive bone imaging, a bone X-ray or MRI evaluation is mandatory to rule out the possibility of metastatic bone scan disease. Other tests may be performed as clinically indicated. It is recommended that all baseline staging should be completed within 35 days prior to study entry.

Exclusion Criteria

• Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
• Prior anthracycline therapy, taxoids or platinum salts for any malignancy.
• Prior radiation therapy for breast cancer or any radiotherapy to the chest wall for any other malignancy.
• Bilateral invasive breast cancer.
• Pregnant or lactating subjects
• Cardiac disease or risk for same as judged by Investigator
• Other serious illness or medical conditions such as (partial list- review with Investigator) history of significant neurologic or psychiatric disorders that would prohibit the understanding and giving of informed consent, active uncontrolled infection, active peptic ulcer, unstable diabetes mellitus or subjects with symptomatic, intrinsic lung disease resulting in dyspnea at rest
• Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention of breast cancer. Subjects must have discontinued these agents prior to study entry.
• Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must be stopped prior to study entry.
• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational non-marketed drug within 30 days prior to study entry.
• Concurrent treatment with any other anti-cancer therapy.
• Male subjects, as no clinical efficacy or safety data are available from phase I-II studies.
• Chemotherapy and/or bevacizumab may not be given until > 7 days following a minor surgical procedure. Chemotherapy may be given without bevacizumab in circumstances in which the participant has recovered sufficiently to receive chemotherapy but has not yet reached a 28 day time point at which bevacizumab could be administered.

• 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

Vicki Erickson, MSN

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Countries

United States

Other Identifiers

DOCET_L_00714

Identifier Type: -

Identifier Source: org_study_id