Phase 2b Study of Taxol Plus Sorafenib or Placebo in Patients With Advanced Breast Cancer

NCT ID: NCT00499525

Last Updated: 2019-05-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Study Completion Date

2022-12-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving paclitaxel together with sorafenib may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well paclitaxel works when given together with or without sorafenib in treating patients with locally recurrent or metastatic breast cancer.

Detailed Description

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OBJECTIVES:

Primary

* Compare progression-free survival of patients with locally recurrent or metastatic breast cancer treated with sorafenib tosylate and paclitaxel versus placebo and paclitaxel as first-line therapy.

Secondary

* Compare the objective response rate and duration of response in patients treated with these regimens.
* Compare the time to progression in patients treated with these regimens.
* Compare the survival of patients treated with these regimens.
* Compare the safety of patients treated with these regimens.
* Compare the change from baseline in the Functional Assessment of Cancer Therapy for Breast Cancer quality of life assessment score in patients treated with these regimens.

OUTLINE: This is a double-blind, randomized, multicenter study. Patients are stratified according to site of metastatic disease (visceral \[i.e., soft internal organs of the body, including lungs, heart, and the organs of the digestive, excretory, and reproductive systems\] vs nonvisceral \[i.e., osseous or soft tissue\] sites). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive paclitaxel IV over 1 hour once weekly for 3 weeks. Patients also receive oral sorafenib tosylate twice daily on days 1-28.
* Arm II: Patients receive paclitaxel as in arm I and oral placebo twice daily on days 1-28.

In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, and every 8 weeks for 24 weeks, and then every 12 weeks for the duration of study participation.

After completion of study therapy, patients are followed every 4 months.

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Arm I

Patients receive paclitaxel IV over 1 hour once weekly for 3 weeks. Patients also receive oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

paclitaxel

Intervention Type DRUG

given IV

sorafenib tosylate

Intervention Type DRUG

given orallly

Arm II

Patients receive paclitaxel as in arm I and oral placebo twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type ACTIVE_COMPARATOR

paclitaxel

Intervention Type DRUG

given IV

placebo

Intervention Type OTHER

given orally

Interventions

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paclitaxel

given IV

Intervention Type DRUG

sorafenib tosylate

given orallly

Intervention Type DRUG

placebo

given orally

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed adenocarcinoma of the breast

* Locally recurrent or metastatic disease

* Locally recurrent disease not amenable to resection with curative intent
* Measurable or evaluable disease
* No HER-2 overexpression (defined as positive for gene amplification by FISH or 3+ overexpression by IHC)

* No unknown HER-2 status
* No active brain metastases

* Patients with neurological symptoms and known brain metastases treated with definitive therapy must undergo contrast CT scan or brain MRI to exclude active brain metastasis

* Previously treated brain metastases allowed provided at least 3 months since prior definitive therapy (including steroids) AND no evidence of disease
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Male or female
* Menopausal status not specified
* ECOG performance status 0-1
* Not pregnant or nursing for ≥ 2 weeks after completion of study therapy
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 2 weeks after completion of study therapy
* Hemoglobin ≥ 9.0 g/dL
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
* ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)
* INR ≤ 1.5 and aPTT within normal limits

* Anticoagulation therapy (e.g., warfarin or heparin) allowed

* Stable INR required for patients on warfarin
* Creatinine ≤ 1.5 times the ULN
* Able to swallow and retain oral medication
* More than 4 weeks since prior significant traumatic injury
* No evidence or history of bleeding diathesis or coagulopathy
* No serious nonhealing wound, ulcer, or bone fracture
* No substance abuse or medical, psychological, or social condition that would interfere with study participation or evaluation of study results
* No pre-existing peripheral neuropathy ≥ grade 2
* No clinically significant cardiac disease, including any of the following:

* New York Heart Association class II-IV congestive heart failure
* Unstable angina (i.e., angina symptoms at rest) or new-onset angina within the past 3 months
* Myocardial infarction within the past 6 months
* No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
* No uncontrolled hypertension (i.e., systolic blood pressure \[BP\] \> 150 mm Hg or diastolic BP \> 90 mm Hg despite optimal medical management)
* No thrombolic, embolic, venous, or arterial events such as a cerebrovascular accident, including transient ischemic attacks within the past 6 months
* No pulmonary hemorrhage or bleeding event \> grade 2 within the past 4 weeks
* No other hemorrhage or bleeding event ≥ grade 3 within the past 4 weeks
* No active clinically serious infection \> grade 2
* No known HIV infection or chronic hepatitis B or C
* No other prior or concurrent cancer except carcinoma in situ of the cervix, treated basal cell skin cancer, superficial bladder tumors (e.g., Ta and Tis), or any cancer curatively treated for \> 5 years
* No known or suspected allergy to sorafenib tosylate or hypersensitivity to paclitaxel or drugs using the vehicle Cremophor

PRIOR CONCURRENT THERAPY:

* More than 12 months since prior adjuvant or neoadjuvant taxane therapy
* At least 3 weeks since other prior adjuvant chemotherapy
* At least 3 weeks since prior hormonal therapy for locally recurrent or metastatic disease
* No prior chemotherapy for locally recurrent or metastatic breast cancer
* More than 4 weeks since prior major surgery or open biopsy
* At least 3 weeks since prior radiotherapy

* Previously irradiated area must not be the only site of disease
* More than 30 days or 5 half-lives, whichever is longer, since prior investigational drug

* No prior or concurrent bevacizumab or any other licensed or investigational drugs that target VEGF or VEGF-receptor
* More than 3 weeks since prior and no concurrent Hypericum perforatum (St. John's wort ) or rifampin (rifampicin)
* No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
* No concurrent irinotecan hydrochloride or doxorubicin hydrochloride
* No other concurrent anticancer therapy (i.e., chemotherapy, radiotherapy, surgery, immunotherapy, biologic therapy, or tumor embolization)
* No concurrent nonconventional therapies (e.g., herbal)
* No concurrent palliative radiotherapy
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

Northwestern University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William J. Gradishar, MD

Role: STUDY_CHAIR

Robert H. Lurie Cancer Center

Locations

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Northwest Alabama Cancer Center, PC - Muscle Shoals

Muscle Shoals, Alabama, United States

Site Status

Highlands Oncology Group - Fayetteville

Fayetteville, Arkansas, United States

Site Status

Pacific Cancer Medical Center, Incorporated

Anaheim, California, United States

Site Status

Pacific Coast Hematology/Oncology Medical Group, Incorporated

Fountain Valley, California, United States

Site Status

Desert Hematology-Oncology Medical Group, Incorporated

Rancho Mirage, California, United States

Site Status

Sutter Cancer Center

Sacramento, California, United States

Site Status

Cancer Prevention and Treatment Center at Dominican and Watsonville Community Hospital

Soquel, California, United States

Site Status

St. Helena, California, United States

Site Status

Helen and Harry Gray Cancer Center at Hartford Hospital

Hartford, Connecticut, United States

Site Status

Eastern Connecticut Hematology and Oncology Associates

Norwich, Connecticut, United States

Site Status

Medical Oncology and Hematology, PC at Harold Leever Cancer Center

Waterbury, Connecticut, United States

Site Status

George Washington University Cancer Institute

Washington D.C., District of Columbia, United States

Site Status

Pasco Hernando Oncology Associates, PA - Brooksville

Brooksville, Florida, United States

Site Status

Pasco Hernando Oncology Associates, PA - New Port Richey

New Port Richey, Florida, United States

Site Status

Northeast Georgia Cancer Care, LLC - Medical Oncology

Athens, Georgia, United States

Site Status

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Boise, Idaho, United States

Site Status

Hematology-Oncology Associates of Illinois

Chicago, Illinois, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Site Status

Decatur Memorial Hospital Cancer Care Institute

Decatur, Illinois, United States

Site Status

Cancer Institute at Alexian Brothers

Elk Grove Village, Illinois, United States

Site Status

Medical and Surgical Specialists, LLC

Galesburg, Illinois, United States

Site Status

Hinsdale Hematology Oncology Associates

Hinsdale, Illinois, United States

Site Status

Midwest Center for Hematology/Oncology

Joliet, Illinois, United States

Site Status

Kellogg Cancer Care Center

Oak Park, Illinois, United States

Site Status

Hematology/Oncology of the North Shore at Gross Point Medical Center

Skokie, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States

Site Status

Family Medicine of Vincennes Clinical Trial Center

Vincennes, Indiana, United States

Site Status

Kentuckiana Cancer Institute, PLLC

Louisville, Kentucky, United States

Site Status

Mary Bird Perkins Cancer Center - Baton Rouge

Baton Rouge, Louisiana, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

Columbia, Missouri, United States

Site Status

Nebraska Hematology-Oncology, PC

Lincoln, Nebraska, United States

Site Status

Essex Oncology of North Jersey

Belleville, New Jersey, United States

Site Status

Sussex County Medical Associates - Sparta

Sparta, New Jersey, United States

Site Status

Piedmont Hematology-Oncology Associates

Winston-Salem, North Carolina, United States

Site Status

Tri-County Hematology/Oncology Associates, Incorporated

Canton, Ohio, United States

Site Status

Hematology Oncology Consultants, Incorporated

Columbus, Ohio, United States

Site Status

North Coast Cancer Care, Incorporated

Sandusky, Ohio, United States

Site Status

Hematology and Oncology Associates of Rhode Island

Cranston, Rhode Island, United States

Site Status

West Clinic - East Memphis

Memphis, Tennessee, United States

Site Status

Patients' Comprehensive Cancer Center - Carrollton

Carrollton, Texas, United States

Site Status

Oncology Consultants - Memorial City

Houston, Texas, United States

Site Status

Cascade Cancer Center at Evergreen Hospital Medical Center

Kirkland, Washington, United States

Site Status

Gundersen Lutheran Center for Cancer and Blood

La Crosse, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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NU 07B1

Identifier Type: OTHER

Identifier Source: secondary_id

STU00000776

Identifier Type: OTHER

Identifier Source: secondary_id

NU 07B1

Identifier Type: -

Identifier Source: org_study_id

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