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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00499525
• Other study ID #: NU 07B1
• Secondary ID: NU 07B1STU000007
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 2007
• Est. completion date: December 2022

Study information

• Verified date: April 2019
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 180
• Est. completion date: December 2022
• Est. primary completion date: December 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• paclitaxel
given IV
• sorafenib tosylate
given orallly

Other:
• placebo
given orally

Locations

Country	Name	City	State
United States	Pacific Cancer Medical Center, Incorporated	Anaheim	California
United States	Northeast Georgia Cancer Care, LLC - Medical Oncology	Athens	Georgia
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	Essex Oncology of North Jersey	Belleville	New Jersey
United States	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho
United States	Pasco Hernando Oncology Associates, PA - Brooksville	Brooksville	Florida
United States	Tri-County Hematology/Oncology Associates, Incorporated	Canton	Ohio
United States	Patients' Comprehensive Cancer Center - Carrollton	Carrollton	Texas
United States	Hematology-Oncology Associates of Illinois	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	Columbia	Missouri
United States	Hematology Oncology Consultants, Incorporated	Columbus	Ohio
United States	Hematology and Oncology Associates of Rhode Island	Cranston	Rhode Island
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Cancer Institute at Alexian Brothers	Elk Grove Village	Illinois
United States	Highlands Oncology Group - Fayetteville	Fayetteville	Arkansas
United States	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana
United States	Pacific Coast Hematology/Oncology Medical Group, Incorporated	Fountain Valley	California
United States	Medical and Surgical Specialists, LLC	Galesburg	Illinois
United States	Helen and Harry Gray Cancer Center at Hartford Hospital	Hartford	Connecticut
United States	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois
United States	Oncology Consultants - Memorial City	Houston	Texas
United States	Midwest Center for Hematology/Oncology	Joliet	Illinois
United States	Cascade Cancer Center at Evergreen Hospital Medical Center	Kirkland	Washington
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Nebraska Hematology-Oncology, PC	Lincoln	Nebraska
United States	Kentuckiana Cancer Institute, PLLC	Louisville	Kentucky
United States	West Clinic - East Memphis	Memphis	Tennessee
United States	Northwest Alabama Cancer Center, PC - Muscle Shoals	Muscle Shoals	Alabama
United States	Pasco Hernando Oncology Associates, PA - New Port Richey	New Port Richey	Florida
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Kellogg Cancer Care Center	Oak Park	Illinois
United States	Desert Hematology-Oncology Medical Group, Incorporated	Rancho Mirage	California
United States	Sutter Cancer Center	Sacramento	California
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Hematology/Oncology of the North Shore at Gross Point Medical Center	Skokie	Illinois
United States	Cancer Prevention and Treatment Center at Dominican and Watsonville Community Hospital	Soquel	California
United States	Sussex County Medical Associates - Sparta	Sparta	New Jersey
United States	Family Medicine of Vincennes Clinical Trial Center	Vincennes	Indiana
United States	George Washington University Cancer Institute	Washington	District of Columbia
United States	Medical Oncology and Hematology, PC at Harold Leever Cancer Center	Waterbury	Connecticut
United States	Piedmont Hematology-Oncology Associates	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		At disease progression or death
Secondary	Overall survival		At time of death
Secondary	Time to progression		At time of disease progression
Secondary	Overall response rate		At the time of progression of disease
Secondary	Duration of overall response		At time of disease progression
Secondary	Treatment-emergent adverse events as assessed by NCI CTCAE v3.0		During treatment and up to 30 days post-treatment