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

Sponsor

Northwestern University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00499525

Collaborator

Amgen (Industry)

180

Enrollment

Locations

Arms

186

Duration (Months)

4.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: paclitaxel Drug: sorafenib tosylate Other: placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2007

Anticipated Primary Completion Date :

Dec 1, 2020

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: paclitaxel given IV Drug: sorafenib tosylate given orallly
Active Comparator: 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.	Drug: paclitaxel given IV Other: placebo given orally

Arm

Intervention/Treatment

Experimental: 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.

Drug: paclitaxel

given IV

Drug: sorafenib tosylate

given orallly

Active Comparator: 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.

Drug: paclitaxel

given IV

Other: placebo

given orally

Outcome Measures

Primary Outcome Measures

Progression-free survival [At disease progression or death]

Secondary Outcome Measures

Overall survival [At time of death]
Time to progression [At time of disease progression]
Overall response rate [At the time of progression of disease]
Duration of overall response [At time of disease progression]
Treatment-emergent adverse events as assessed by NCI CTCAE v3.0 [During treatment and up to 30 days post-treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwest Alabama Cancer Center, PC - Muscle Shoals	Muscle Shoals	Alabama	United States	35661
2	Highlands Oncology Group - Fayetteville	Fayetteville	Arkansas	United States	72703
3	Pacific Cancer Medical Center, Incorporated	Anaheim	California	United States	92801
4	Pacific Coast Hematology/Oncology Medical Group, Incorporated	Fountain Valley	California	United States	92708
5	Desert Hematology-Oncology Medical Group, Incorporated	Rancho Mirage	California	United States	92270
6	Sutter Cancer Center	Sacramento	California	United States	95816
7		Saint Helena	California	United States	94574
8	Cancer Prevention and Treatment Center at Dominican and Watsonville Community Hospital	Soquel	California	United States	95073
9	Helen and Harry Gray Cancer Center at Hartford Hospital	Hartford	Connecticut	United States	06102-5037
10	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
11	Medical Oncology and Hematology, PC at Harold Leever Cancer Center	Waterbury	Connecticut	United States	06708
12	George Washington University Cancer Institute	Washington	District of Columbia	United States	20037
13	Pasco Hernando Oncology Associates, PA - Brooksville	Brooksville	Florida	United States	34613
14	Pasco Hernando Oncology Associates, PA - New Port Richey	New Port Richey	Florida	United States	34652
15	Northeast Georgia Cancer Care, LLC - Medical Oncology	Athens	Georgia	United States	30607
16	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
17	Hematology-Oncology Associates of Illinois	Chicago	Illinois	United States	60611-2998
18	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
19	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
20	Cancer Institute at Alexian Brothers	Elk Grove Village	Illinois	United States	60007-3397
21	Medical and Surgical Specialists, LLC	Galesburg	Illinois	United States	61401
22	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois	United States	60521
23	Midwest Center for Hematology/Oncology	Joliet	Illinois	United States	60432
24	Kellogg Cancer Care Center	Oak Park	Illinois	United States	60302
25	Hematology/Oncology of the North Shore at Gross Point Medical Center	Skokie	Illinois	United States	60076
26	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46885-5099
27	Family Medicine of Vincennes Clinical Trial Center	Vincennes	Indiana	United States	47591
28	Kentuckiana Cancer Institute, PLLC	Louisville	Kentucky	United States	40202
29	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana	United States	70809-3482
30	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	Columbia	Missouri	United States	65201
31	Nebraska Hematology-Oncology, PC	Lincoln	Nebraska	United States	68510-2482
32	Essex Oncology of North Jersey	Belleville	New Jersey	United States	07109
33	Sussex County Medical Associates - Sparta	Sparta	New Jersey	United States	07871
34	Piedmont Hematology-Oncology Associates	Winston-Salem	North Carolina	United States	27103
35	Tri-County Hematology/Oncology Associates, Incorporated	Canton	Ohio	United States	44718
36	Hematology Oncology Consultants, Incorporated	Columbus	Ohio	United States	43235
37	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
38	Hematology and Oncology Associates of Rhode Island	Cranston	Rhode Island	United States	02920
39	West Clinic - East Memphis	Memphis	Tennessee	United States	38120
40	Patients' Comprehensive Cancer Center - Carrollton	Carrollton	Texas	United States	75010-4602
41	Oncology Consultants - Memorial City	Houston	Texas	United States	77024
42	Cascade Cancer Center at Evergreen Hospital Medical Center	Kirkland	Washington	United States	98034-3013
43	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601