Sorafenib in Treating Patients With Metastatic Breast Cancer

Phase II Trial of Raf Kinase Inhibitor BAY 43-9006 as Single Oral Agent in Patients With Metastatic Breast Cancer Previously Exposed to Anthracycline and/or Taxane

This phase II trial is studying how well sorafenib works in treating patients with metastatic breast cancer. Sorafenib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor.

Study Overview

• Status: Completed
• Conditions: Male Breast Cancer; Stage IV Breast Cancer; Recurrent Breast Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: sorafenib tosylate

Detailed Description

OBJECTIVES:

I. Determine the tumor response rate in patients with metastatic breast cancer previously treated with an anthracycline- and/or taxane-containing regimen receiving sorafenib.

II. Assess the toxicity profile of this drug in these patients. III. Determine time to disease progression and survival time of patients treated with this drug.

IV. Correlate pre-treatment levels of activated ERK1/2 with tumor response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months until disease progression and then every 3 months for up to 5 years.

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • North Central Cancer Treatment Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed breast cancer

  • Clinical evidence of metastatic disease
• Measurable disease

• HER2-positive or -negative disease

  • If HER2 gene amplified or strongly positive for HER2 by immunohistochemistry, patient must have had prior treatment containing trastuzumab (Herceptin®) unless contraindicated
• Previously treated with anthracycline- and/or taxane-containing regimen in the neoadjuvant, adjuvant, or metastatic setting
• Candidate for first- or second-line chemotherapy for metastatic disease
• Core block or tumor slides of the primary or metastatic tumor available
• No known brain metastases

• Hormone receptor status:

  • Not specified
• Male or female
• Performance status - ECOG 0-1
• At least 3 months
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.5 g/dL
• No evidence of bleeding diathesis
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST ≤ 3 times ULN
• Alkaline phosphatase ≤ 3 times ULN
• PT normal
• PTT normal
• INR normal
• Creatinine ≤ 1.5 times ULN
• Calcium normal
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No uncontrolled hypertension
• No gastrointestinal tract disease that would preclude taking oral medication
• No active peptic ulcer disease
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to sorafenib or other study agents
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No other uncontrolled illness
• See Disease Characteristics
• More than 4 weeks since prior immunotherapy
• No concurrent anticancer immunotherapy
• No concurrent bevacizumab
• See Disease Characteristics
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No more than 1 prior chemotherapy regimen for metastatic disease
• No concurrent anticancer chemotherapy
• Prior hormonal therapy in the neoadjuvant, adjuvant, or metastatic setting is allowed
• No concurrent anticancer hormonal therapy
• No prior radiotherapy to ≥ 25% of the bone marrow
• More than 4 weeks since prior radiotherapy
• More than 4 weeks since prior major surgery
• No prior surgical procedure that would affect gastrointestinal absorption
• No other concurrent drugs that target vascular endothelial growth factor (VEGF) or VEGF receptors
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy

• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs, including any of the following:

  • Phenytoin
  • Carbamazepine
  • Phenobarbital
• No concurrent rifampin
• No concurrent Hypericum perforatum (St. John's wort)

• No concurrent therapeutic anticoagulation

  • Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial devices is allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: sorafenib tosylate; Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of confirmed tumor responses, graded according to RECIST criteria	A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. The tumor response rate is defined as the total number of eligible patients who achieved a complete or partial response according to the RECIST criteria divided by the total number of eligible patients enrolled on study. A 90% confidence interval for the true response rate will be constructed using the Duffy-Santner approach.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression	Estimated using the Kaplan-Meier method.	Time from registration to disease progression, assessed up to 5 years
Survival time	Estimated using the Kaplan-Meier method.	Time from registration to death, assessed up to 5 years
Incidence of adverse events, graded according to the NCI-CTC version 3	The maximum grade for each type of toxicity will be recorded for each patient at each treatment evaluation. The frequency of each type of toxicity will be determined.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Edith Perez, North Central Cancer Treatment Group

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: November 9, 2004
• First Submitted That Met QC Criteria: November 9, 2004
• First Posted (Estimated): November 10, 2004

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Breast Neoplasms, Male; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: NCI-2012-01817 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA025224 (U.S. NIH Grant/Contract); CDR0000393224; NCCTG-N0336; N0336 (Other Identifier: CTEP)