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

NCT00446030 | Completed Phase 2 Results DMC

• 1 other identifier: DOCET_L_00713
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With Grade 3/4 Clinical Congestive Heart Failure (CHF)

  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.

  up to 2 years

Secondary Outcomes (1)

• Disease-free Survival (DFS) & Overall Survival (OS) of Participants

  up to 10 years

Study Arms (2)

Stratum 1: TAC + Bevacizumab

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Bevacizumab

Stratum 2: TCH + Bevacizumab

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Carboplatin; Drug: Trastuzumab; Drug: Bevacizumab

Interventions

Docetaxel DRUG

75 mg/m\^2 administered IV on Day 1 for Cycles 1-6 All participants received a prophylactic steroid regimen prior to each dose of docetaxel - Dexamethasone 8 mg orally 12 hours prior to docetaxel, dexamethasone 10 mg IV just prior the docetaxel infusion and 8 mg orally 12 hours after docetaxel administration. If a participant had not taken their oral dexamethasone the evening prior to receiving docetaxel, the dose of the pre-docetaxel infusion of dexamethasone was increased from 10 mg IV to 15 mg IV. A Dexamethasone 8 mg equivalent may have been used (dexamethasone 8 mg = methylprednisolone 40 mg = prednisone 50 mg = prednisolone 50 mg).

Also known as: Taxotere®

Stratum 1: TAC + Bevacizumab; Stratum 2: TCH + Bevacizumab

Doxorubicin DRUG

50 mg/m\^2 administered IV on Day 1 for Cycles 1-6

Stratum 1: TAC + Bevacizumab

Carboplatin DRUG

6 mg/mL/min (target area under the curve \[AUC\] dose) administered IV on Day 1 for Cycles 1-6

Also known as: Gemzar®

Stratum 2: TCH + Bevacizumab

Cyclophosphamide DRUG

500 mg/m\^2 administered IV on Day 1 for Cycles 1-6

Stratum 1: TAC + Bevacizumab

Trastuzumab DRUG

A single loading dose of 8 mg/kg administered IV on Day 2 for Cycle 1, and 6 mg/kg administered IV on Day 1 for Cycles 2-6 and for maintenance therapy

Stratum 2: TCH + Bevacizumab

Bevacizumab DRUG

15 mg/kg administered IV on Day 1 for Cycles 1-6, and for maintenance therapy

Stratum 1: TAC + Bevacizumab; Stratum 2: TCH + Bevacizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• age \<35 years
• Were participants with the Human Epidermal growth factor Receptor 2 (HER2/neu) status (positive or negative) known at the time of signing the informed consent
• Had the estrogen and progesterone receptor status known prior to study registration
• Had Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Had normal cardiac function, confirmed by left ventricular ejection fraction (LVEF) or shortening fraction (echocardiography \[ECHO\] or multiple-gated acquisition \[MUGA\] scan respectively)

You may not qualify if:

• 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
• Grade 3 or Grade 4 cardiac arrhythmia (NCI CTCAE, version 3.0)
• Clinically significant valvular heart disease
• Had cardiomegaly
• Had poorly controlled hypertension, i.e., diastolic greater than 100 mmHg. (Participants who were well controlled on medication were eligible)
• Were currently receiving medications administered for cardiac arrhythmia, angina or congestive heart failure (e.g., digitalis, beta-blockers, calcium channel-blockers), that alter cardiac conduction, unless the medications were administered for other reasons (e.g., hypertension)

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

Related Publications (1)

• Hurvitz SA, Bosserman LD, Chan D, Hagenstad CT, Kass FC, Smith FP, Rodriguez GI, Childs BH, Slamon DJ. Cardiac safety results from a phase II, open-label, multicenter, pilot study of two docetaxel-based regimens plus bevacizumab for the adjuvant treatment of subjects with node-positive or high-risk node-negative breast cancer. Springerplus. 2014 May 12;3:244. doi: 10.1186/2193-1801-3-244. eCollection 2014.

  PMID: 24860718 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; Doxorubicin; Carboplatin; Gemcitabine; Cyclophosphamide; Trastuzumab; Bevacizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Coordination Complexes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; 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

Limitations and Caveats

The number of participants enrolled into the TCH with bevacizumab arm was reduced to half of the originally intended number. Therefore, all conclusions related to the safety of TCH with bevacizumab must be interpreted with caution.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: sanofi-aventis

Contact-us@sanofi-aventis.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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2007
• First Posted: March 12, 2007
• Study Start: March 1, 2007
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: June 26, 2012
• Results First Posted: November 4, 2011

Record last verified: 2012-06

Locations

US (1)