Trial of Paclitaxel/Bevacizumab +/- Everolimus for Patients With HER2-Negative Metastatic Breast Cancer

NCT00915603 | Completed Phase 2 Results

• 1 other identifier: SCRI BRE 154
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 15

Brief Summary

This randomized, double blind, placebo controlled trial will evaluate the impact of adding everolimus to the combination of weekly paclitaxel plus bevacizumab in the first-line treatment of women with HER2-negative metastatic breast cancer. Patients will be randomized (1:1) to receive either paclitaxel/bevacizumab/everolimus (Treatment Arm 1) or paclitaxel/ bevacizumab/placebo (Treatment Arm 2). Patients will be evaluated for response to treatment every 8 weeks; responding and/or stable patients will continue treatment, with re-evaluations every 8 weeks, until tumor progression or intolerable toxicity occurs. Outcomes will be assessed for each treatment arm separately. This trial is not intended to compare treatment arms primarily. Any such analyses are exploratory and will be conducted without adjustment for multiple hypothesis testing.

Conditions

Metastatic Breast Cancer

Keywords

Metastatic Breast Cancer; Paclitaxel; Bevacizumab; Everolimus

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-free survival will be measured from Day 1 of study drug administration to disease progression defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  every 8 weeks until progressive disease, expected average of 18 months

Secondary Outcomes (4)

• Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability

  every 4 weeks until intolerable toxicity occurs

• Overall Response Rate (ORR)

  every 8 weeks until treatment discontinuation, expected average of 18 months

• Duration of Response (DOR)

  every 8 weeks until treatment discontinuation, expected average 6 months

• Overall Survival (OS)

  every 8 weeks until treatment discontinuation, expected average 6 months

Study Arms (2)

paclitaxel/bevacizumab/everolimus

ACTIVE COMPARATOR

Systemic Therapy

Drug: Everolimus; Drug: Bevacizumab; Drug: Paclitaxel

paclitaxel/bevacizumab/placebo

PLACEBO COMPARATOR

Systemic Therapy

Drug: Placebo; Drug: Bevacizumab; Drug: Paclitaxel

Interventions

Everolimus DRUG

Everolimus 10mg PO daily continuously for all 28 days of a cycle

Also known as: Systemic therapy, RAD001, Afinitor

paclitaxel/bevacizumab/everolimus

Bevacizumab DRUG

Bevacizumab 10mg/kg IV Days 1 and 15 of 28 day cycle

Also known as: Systemic therapy, Avastin

paclitaxel/bevacizumab/everolimus

Paclitaxel DRUG

Paclitaxel 90mg/m2 1-hour IV infusion Days 1, 8 and 15 of 28 day cycle. Patients will receive standard pre-medication before each paclitaxel treatment to prevent a hypersensitivity reaction.

Also known as: Systemic therapy, Taxol

paclitaxel/bevacizumab/everolimus

Placebo DRUG

Placebo PO daily continuously for all 28 days of a cycle

Also known as: Systemic therapy

paclitaxel/bevacizumab/placebo

Eligibility Criteria

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

You may qualify if:

• Female or male patients \>=18 years of age.
• Histologically confirmed invasive breast cancer, locally unresectable or metastatic.
• No prior chemotherapy for MBC. Patients may have received adjuvant or
• neoadjuvant chemotherapy (including taxanes and/or bevacizumab) as long as
• treated was completed \>12 months prior to relapse. Prior hormonal therapy in the
• adjuvant or metastatic setting will be permitted.
• Prior hormonal therapy in the adjuvant or metastatic setting is permitted. Estrogen receptor positive patients should be considered candidates for chemotherapy.
• HER2-negative breast cancer, defined as follows:
• FISH-negative (FISH ratio \<2.2), or
• IHC 0-1+, or
• IHC 2-3+ AND FISH-negative (FISH ratio \<2.2).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Adequate hematologic function, defined by:
• · Absolute neutrophil count (ANC) \>1500/mm3
• Platelet count \>=100,000/mm3

You may not qualify if:

• Patients with active brain metastases or meningeal metastases. Patients who have had brain metastases resected, or have received brain radiation therapy \>4 weeks prior to study entry are eligible, if they meet all of the following criteria: 1) residual symptoms \< grade 2, 2) no dexamethasone requirement, and 3) follow-up MRI shows regression of lesions after treatment and no new lesions appearing.
• Previous treatment with an m-TOR inhibitor (sirolimus, temsirolimus, everolimus) or anti-angiogenesis agent unless:
• in the adjuvant setting, and
• \>=12 months prior to recurrence.
• Previous radiotherapy for metastatic disease completed \<2 weeks prior to study treatment initiation.
• Patients who are current receiving systemic cancer therapy or have received
• previous systemic therapy within 4 weeks of the start of study drug (e.g.
• chemotherapy, antibody therapy, targeted agents).
• Women who are pregnant or lactating. All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug.
• Uncontrolled hypertension defined as systolic blood pressure \>150 mmHg or
• diastolic pressure \>100 mmHg, despite optimal medical management.
• Concurrent use of CYP3A4 inhibitors and inducers from 72 hours prior to initiation of study treatment until the end of treatment with everolimus.
• Cardiac disease, including: congestive heart failure (CHF) \> Class II per New York Heart Association (NYHA) classification; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• History of stroke or transient ischemic attack within 6 months prior to first
• bevacizumab dose.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis: collaborator

Study Sites (15)

Wilshire Oncology Medical Group

LaVerne, California, 91750, United States

Location

Eastern Connecticut Hematology Oncology

Norwich, Connecticut, 06360, United States

Location

Aventura Medical Center

Aventura, Florida, 33180, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Mercy Hospital

Portland, Maine, 04101, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

National Capital Clinical Research Associates

Bethesda, Maryland, 20817, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center

Columbus, Ohio, 43219, United States

Location

South Carolina Oncology Associates, PA

Columbia, South Carolina, 29210, United States

Location

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

Texas Oncology

Dallas, Texas, 75246, United States

Location

Fairfax Northern Virginia Hem-Onc

Fairfax, Virginia, 22031, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23235, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; Bevacizumab; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: John D. Hainsworth, MD
• Organization: Sarah Cannon Research Institute

asksarah@scresearch.net

1-877-691-7274

Study Officials

• Denise A. Yardley, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2009
• First Posted: June 8, 2009
• Study Start: July 1, 2009
• Primary Completion: June 1, 2014
• Study Completion: July 1, 2014
• Last Updated: December 22, 2014
• Results First Posted: December 22, 2014

Record last verified: 2014-12

Locations

US (15)