Sorafenib and Letrozole, Anastrozole, or Exemestane in Treating Postmenopausal Women With Estrogen Receptor-Positive and/or Progesterone Receptor-Positive Metastatic Breast Cancer

NCT00573755 | Terminated Phase 2 Results DMC

• 3 other identifiers: RC0731P30CA01508307-005768
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Aromatase inhibition therapy using letrozole, anastrozole, or exemestane may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether sorafenib is more effective than a placebo when given together with letrozole, anastrozole, or exemestane in treating metastatic breast cancer. PURPOSE: This randomized phase II trial is studying how well sorafenib works compared with a placebo when given together with letrozole, anastrozole, or exemestane in treating postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive metastatic breast cancer.

Conditions

Breast Cancer

Keywords

stage IV breast cancer; recurrent breast cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression-free survival was defined as the time from randomization to the earliest date of documentation of disease progression or death due to any cause. In the case of a participant started treatment and then never return for any evaluations, the participant was censored for progression 1 day post-randomization.

  Time from randomization to disease progression or death (up to 5 years)

Secondary Outcomes (5)

• Overall Survival

  Time from randomization to death (up to 5 years)

• Time to Treatment Failure

  Time from randomization to treatment failure (up to 5 years)

• Objective Tumor Response Rate

  Up to 5 years

• Duration of Response

  Up to 5 years

• Adverse Event

  Time from randomization to end of treatment

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive oral sorafenib tosylate twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: anastrozole; Drug: exemestane; Drug: letrozole; Drug: sorafenib tosylate

Arm II

ACTIVE COMPARATOR

Patients receive oral placebo twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: anastrozole; Drug: exemestane; Drug: letrozole; Other: placebo

Interventions

anastrozole DRUG

given orally

Arm I; Arm II

exemestane DRUG

given orally

Arm I; Arm II

letrozole DRUG

given orally

Arm I; Arm II

sorafenib tosylate DRUG

given orally

Arm I

placebo OTHER

given orally

Arm II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed adenocarcinoma of the breast * Metastatic disease * Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (i.e., MRI or CT scan of chest, abdomen and pelvis) or ≥ 10 mm by spiral CT scan * Non-measurable disease allowed, defined as all other lesions (or sites of disease), including small lesions (longest diameter \< 20 mm by conventional techniques or \< 10 mm by spiral CT scan) * Must have objective evidence of progression within the past 3 months * No human epidermal growth factor receptor 2 (HER2)/neu overexpression, defined as gene amplification by fluorescence in situ hybridization or 3+ overexpression by immunohistochemistry, or unknown HER2/neu status * No active brain metastases * Patients with neurological symptoms must undergo a contrast CT scan or MRI of the brain to exclude active brain metastasis * Patients with treated brain metastases allowed provided they have no evidence of disease and have been off definitive therapy (including steroids) for the past 3 months * Hormone receptor status: * Estrogen receptor- and/or progesterone receptor-positive disease PATIENT CHARACTERISTICS: * Female * The Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Postmenopausal * Hemoglobin ≥ 9.0 g/dL * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement) * INR ≤ 1.5 * PTT within normal limits * Creatinine ≤ 1.5 times ULN * Not nursing, pregnant, or able to become pregnant * No significant traumatic injury within the past 4 weeks * No history of bleeding diathesis or uncontrolled coagulopathy * No serious, nonhealing wound, ulcer, or bone fracture * No clinically significant cardiac disease, including any of the following: * New York Heart Association class III-IV congestive heart failure * Unstable angina (i.e., anginal symptoms at rest) or new-onset angina (i.e., began within the past 3 months) * Myocardial infarction within the past 6 months * No cardiac ventricular arrhythmias requiring antiarrhythmic therapy * No uncontrolled hypertension (systolic BP \> 150 mm Hg or diastolic BP \> 90 mm Hg), despite optimal medical management * No thrombolic, embolic, venous, or arterial events (e.g., 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 * No chronic hepatitis B or C infection * No previous or concurrent cancer that is distinct in primary site or histology from breast cancer except carcinoma in situ of the cervix, treated basal cell skin cancer, superficial bladder tumors (i.e., Ta and Tis), or any cancer curatively treated within the past 5 years * No known or suspected allergy to sorafenib tosylate or other agents used in this study PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No major surgery or open biopsy within the past 4 weeks * No more than 1 prior regimen of endocrine therapy for metastatic breast cancer, provided that the patient has not received an aromatase inhibitor within the past 12 months * No more than 1 prior regimen of chemotherapy for metastatic disease * More than 2 weeks since prior radiotherapy, except if to a non-target lesion only or single-dose radiotherapy for palliation * Prior radiotherapy to a target lesion(s) is permitted only if there has been clear progression of the lesion since radiotherapy was completed * Concurrent anticoagulation treatment (e.g., warfarin or heparin) allowed * No concurrent Hypericum perforatum (St. John's wort), rifampin, bevacizumab, or any other drugs (licensed or investigational) that target vascular endothelial growth factor (VEGF) or VEGF receptors * No concurrent cytochrome P450 enzyme-inducing anti-epileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 55259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; exemestane; Letrozole; Sorafenib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Results Point of Contact

• Title: Dr. Vivek Roy
• Organization: Mayo Clinic

roy.vivek@mayo.edu

507-284-1159

Study Officials

• Vivek Roy, MD

  Mayo Clinic

  STUDY CHAIR

• Donald W Northfelt, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Timothy J Hobday, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2007
• First Posted: December 14, 2007
• Study Start: December 1, 2007
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: February 5, 2016
• Results First Posted: March 26, 2014

Record last verified: 2015-10

Locations

US (3)