Clinical trial NCT00499525: Phase 2b Study of Taxol Plus Sorafenib or Placebo in Patients With Advanced Breast Cancer
Official title: A Double-Blind, Randomized Phase 2b Study Evaluating the Efficacy and Safety of Sorafenib Compared to Placebo When Administered in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Keywords: male breast cancer
recurrent breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
stage IIIA breast cancer
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2007-07-11
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Progression-free survival
timeFrame: At disease progression or death
Secondary outcomes:
measure: Overall survival
timeFrame: At time of death
measure: Time to progression
timeFrame: At time of disease progression
measure: Overall response rate
timeFrame: At the time of progression of disease
measure: Duration of overall response
timeFrame: At time of disease progression
measure: Treatment-emergent adverse events as assessed by NCI CTCAE v3.0
timeFrame: During treatment and up to 30 days post-treatment
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
facility: Northwest Alabama Cancer Center, PC - Muscle Shoals
state: Alabama
city: Fayetteville
country: United States
facility: Highlands Oncology Group - Fayetteville
state: Arkansas
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Incorporated
state: California
city: Fountain Valley
country: United States
facility: Pacific Coast Hematology/Oncology Medical Group, Incorporated
state: California
city: Rancho Mirage
country: United States
facility: Desert Hematology-Oncology Medical Group, Incorporated
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: Saint Helena
country: United States
state: California
city: Soquel
country: United States
facility: Cancer Prevention and Treatment Center at Dominican and Watsonville Community Hospital
state: California
city: Hartford
country: United States
facility: Helen and Harry Gray Cancer Center at Hartford Hospital
state: Connecticut
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Waterbury
country: United States
facility: Medical Oncology and Hematology, PC at Harold Leever Cancer Center
state: Connecticut
city: Washington
country: United States
facility: George Washington University Cancer Institute
state: District of Columbia
city: Brooksville
country: United States
facility: Pasco Hernando Oncology Associates, PA - Brooksville
state: Florida
city: New Port Richey
country: United States
facility: Pasco Hernando Oncology Associates, PA - New Port Richey
state: Florida
city: Athens
country: United States
facility: Northeast Georgia Cancer Care, LLC - Medical Oncology
state: Georgia
city: Boise
country: United States
facility: Mountain States Tumor Institute at St. Luke's Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: Hematology-Oncology Associates of Illinois
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Elk Grove Village
country: United States
facility: Cancer Institute at Alexian Brothers
state: Illinois
city: Galesburg
country: United States
facility: Medical and Surgical Specialists, LLC
state: Illinois
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates
state: Illinois
city: Joliet
country: United States
facility: Midwest Center for Hematology/Oncology
state: Illinois
city: Oak Park
country: United States
facility: Kellogg Cancer Care Center
state: Illinois
city: Skokie
country: United States
facility: Hematology/Oncology of the North Shore at Gross Point Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Vincennes
country: United States
facility: Family Medicine of Vincennes Clinical Trial Center
state: Indiana
city: Louisville
country: United States
facility: Kentuckiana Cancer Institute, PLLC
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center - Baton Rouge
state: Louisiana
city: Columbia
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Hematology-Oncology, PC
state: Nebraska
city: Belleville
country: United States
facility: Essex Oncology of North Jersey
state: New Jersey
city: Sparta
country: United States
facility: Sussex County Medical Associates - Sparta
state: New Jersey
city: Winston-Salem
country: United States
facility: Piedmont Hematology-Oncology Associates
state: North Carolina
city: Canton
country: United States
facility: Tri-County Hematology/Oncology Associates, Incorporated
state: Ohio
city: Columbus
country: United States
facility: Hematology Oncology Consultants, Incorporated
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care, Incorporated
state: Ohio
city: Cranston
country: United States
facility: Hematology and Oncology Associates of Rhode Island
state: Rhode Island
city: Memphis
country: United States
facility: West Clinic - East Memphis
state: Tennessee
city: Carrollton
country: United States
facility: Patients' Comprehensive Cancer Center - Carrollton
state: Texas
city: Houston
country: United States
facility: Oncology Consultants - Memorial City
state: Texas
city: Kirkland
country: United States
facility: Cascade Cancer Center at Evergreen Hospital Medical Center
state: Washington
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: William J. Gradishar, MD
role: STUDY_CHAIR
References: