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

NCT00365365 | Completed Phase 2 Results DMC

• 1 other identifier: DOCET_L_00714
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Cardiac Safety - Number of Participants With Grade 3-4 Clinical Congestive Heart Failure (CHF)

  Participants were evaluated for clinical CHF every 3 weeks during chemotherapy, every 3 months while on maintenance therapy, and every 3 months during the 2-year follow-up period. Left ventricular ejection fraction (LVEF) of CHF was assessed by multi-gated acquisition (MUGA) or echocardiogram (ECHO) performed midway through completion of chemotherapy according to a treatment-specific schedule, every 12 weeks during maintenance therapy, and at 6 and 24 months after completion of maintenance therapy. Grade 3-4 CHF were identified through a clinical review of all study collected investigator verbatim and the Medical Dictionary for Regulatory Activities (MedDRA). The preferred terms (PT) cardiac failure congestive, cardiomyopathy, and ejection fraction decreased were associated with CHF.

  from the first dose of study medication up to the end of follow-up (up to 3 yrs)

Secondary Outcomes (2)

• Safety - Number of Participants With Adverse Events (AE)

  from the administration of the first dose of study medication up to 30 days after the last dose of study medication; events ongoing at the time of discontinuation were monitored in the follow-up period until resolution.

• Disease-free Survival (DFS) Rate

  from the administration of the first-dose of study medication up to 12 months, 18 months and 24 months

Study Arms (3)

Stratum 1 (AC->T + bevacizumab)

EXPERIMENTAL

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

Drug: Doxorubicin and cyclophosphamide (AC) + bevacizumab; Drug: Docetaxel (T) + bevacizumab; Drug: Bevacizumab maintenance therapy

Stratum 2 (TAC + bevacizumab)

EXPERIMENTAL

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

Drug: Docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab; Drug: Bevacizumab maintenance therapy

Stratum 3 (TCH + bevacizumab)

EXPERIMENTAL

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

Drug: Docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab; Drug: Bevacizumab and trastuzumab maintenance therapy

Interventions

Doxorubicin and cyclophosphamide (AC) + bevacizumab 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

Also known as: Avastin® (bevacizumab), Adriamycin® (doxorubicin)

Stratum 1 (AC->T + bevacizumab)

Docetaxel (T) + bevacizumab 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

Also known as: Taxotere® (docetaxel), Avastin® (bevacizumab)

Stratum 1 (AC->T + bevacizumab)

Docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab 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

Also known as: Taxotere® (docetaxel), Avastin® (bevacizumab)

Stratum 2 (TAC + bevacizumab)

Docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab 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

Also known as: Taxotere® (docetaxel), Herceptin® (trastuzumab), Avastin® (bevacizumab)

Stratum 3 (TCH + bevacizumab)

Bevacizumab and trastuzumab maintenance therapy 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.

Also known as: Avastin® (bevacizumab), Herceptin® (trastuzumab)

Stratum 3 (TCH + bevacizumab)

Bevacizumab maintenance therapy 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.

Also known as: Avastin® (bevacizumab)

Stratum 1 (AC->T + bevacizumab); Stratum 2 (TAC + bevacizumab)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Bevacizumab; Docetaxel; Carboplatin; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Coordination Complexes

Limitations and Caveats

The study was originally designed to last for 6-10 years. Based on a protocol amendment, the study was shortened to about 3 years, and the endpoint Overall Survival (OS) was deleted.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact_Us@sanofi.com

Study Officials

• Vicki Erickson, MSN

  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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2006
• First Posted: August 17, 2006
• Study Start: August 1, 2006
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: September 14, 2012
• Results First Posted: September 14, 2012

Record last verified: 2012-01

Locations

US (1)