Phase II Trial of Capecitabine With Fulvestrant for Postmenopausal Women With Hormone Receptor Positive Metastatic Breast Cancer

NCT ID: NCT00534417

Last Updated: 2013-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2011-09-30

Brief Summary

The purpose of this study is to determine if the combination of continuous daily capecitabine with fulvestrant on a loading dose schedule will delay disease progression in metastatic breast cancer (MBC) patients.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Capecitabine and fulvestrant

Capecitabine will be given on a continuous basis at a total dose of 1500 mg, given as 1000 mg po AM and 500 mg po PM in patients of body weight < 80 kg, and at a total dose of 2000 mg given as 1000 mg po bid in patients with a body weight of ≥80 kg.

Fulvestrant will be given at 500 mg on Day 1 followed by 250 mg on Days 15 and 29, then 250 mg every 28 days.

Group Type: EXPERIMENTAL

capecitabine

Intervention Type: DRUG

Capecitabine will be given on a continuous basis at a total dose of 1500 mg, given as 1000 mg po in the morning (AM) and 500 mg po in the evening (PM) in patients of body weight \< 80 Kg, and at a total dose of 2000 mg given as 1000 mg po bid in patients with a body weight of ≥80 Kg.

fulvestrant

Intervention Type: DRUG

Fulvestrant will be given at 500mg on Day 1 followed by 250 mg on Days 15 and 29, then 250mg every 28 days(Q28d).

Interventions

capecitabine

Capecitabine will be given on a continuous basis at a total dose of 1500 mg, given as 1000 mg po in the morning (AM) and 500 mg po in the evening (PM) in patients of body weight \< 80 Kg, and at a total dose of 2000 mg given as 1000 mg po bid in patients with a body weight of ≥80 Kg.

Intervention Type: DRUG

fulvestrant

Fulvestrant will be given at 500mg on Day 1 followed by 250 mg on Days 15 and 29, then 250mg every 28 days(Q28d).

Intervention Type: DRUG

Other Intervention Names

Xeloda; Faslodex

Eligibility Criteria

Inclusion Criteria

• Provide written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
• At least 18 years of age.
• Post-menopausal female (ie, amenorrheic for at least 12 months prior to study entry). Post-menopausal status will be confirmed by drawing follicle stimulating hormone (FSH) and estradiol levels if < 2 years since last menses.
• Ambulatory outpatient with Eastern Cooperative Oncology Group (ECOG)performance status of 0 to 2 at study entry.
• Primary tumor human epidermal growth factor receptor 2 (HER-2) negative at study entry.(Investigator discretion will be used in instances of immuno-histochemistry [IHC] 2+.)
• Histologically or cytologically confirmed MBC.
• Primary tumor and/or metastatic lesion estrogen receptor + and/or progesterone receptor + by IHC.
• At least one measurable or evaluable(non-measurable) lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (see Appendix 11.6) which has not been irradiated (i.e., newly arising lesions in previously irradiated areas are accepted). Ascites, pleural effusion, and bone metastases are not considered measurable but are considered evaluable (non-measurable). Minimum indicator lesion size for measurable disease: ≥10 mm measured by spiral computed tomography (CT) or ≥20 mm measured by conventional techniques.
• Adequate hematologic, renal, and hepatic function.

• Hematologic values: Neutrophils (ANC) > 1.5 x 109/L; Platelet count > 100 x 109/L.
• Renal function: estimated creatinine clearance > 30 mL/min as calculated with Cockcroft-Gault equation.
• Note: In patients with moderate renal impairment (calculated creatinine clearance 30 to 50 mL/min) at baseline, a dose reduction to (-1) of the capecitabine starting dose is required.
• Serum bilirubin < 1.5 x upper limit normal (ULN).
• Alanine transaminase (ALT) or aspartate transaminase (AST) < 2.5 x ULN (or < 5 x ULN in the case of liver metastases).
• Alkaline phosphatase < 2.5 x ULN (or < 5 x ULN in the case of liver metastases or < 10 x ULN in the case of bone disease).
• International normalization ratio (INR) < 1.6.
• Must have ≤ 1 prior regimen of endocrine therapy for metastatic breast cancer. This would include patients who have a recurrence while on adjuvant hormone therapy OR have first recurrence after adjuvant hormone therapy OR progressed after first line hormone therapy for metastatic breast cancer OR treatment naïve patients who present with metastatic breast cancer.

Exclusion Criteria

• Prior administration of capecitabine.
• Prior administration of fulvestrant.
• Prior chemotherapy for metastatic breast cancer.
• Radiotherapy ≤ 2 weeks prior to registration, except if to a non-target lesion only or single-dose radiation for palliation. NOTE: Prior radiation to a target lesion(s) is permitted only if there has been clear progression of the lesion since radiation was completed.
• Life expectancy <3 months.
• Serious, uncontrolled, concurrent infection(s).
• Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Treatment for other carcinomas within the last 5 years, except cured non-melanoma skin and treated in-situ cervical cancer or superficial bladder tumors (stage Ta or Tis).
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• Clinically significant cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication)or myocardial infarction within the last 12 months prior to study entry.
• Active brain metastases. Patients with neurological symptoms must undergo a CT scan or magnetic resonance imaging (MRI) of the brain to exclude active brain metastasis. NOTE: Patients with treated brain metastases are eligible provided they have no evidence of disease and are off definitive therapy (including steroids) ≥ 3 months prior to study entry.
• Central nervous system (CNS) disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
• Known human immunodeficiency virus or chronic hepatitis B or C.
• Other serious uncontrolled medical conditions that the investigator feels might compromise study participation.
• Major surgery within 4 weeks of the start of study treatment, without complete recovery.
• Lack of physical integrity of the upper GI tract or malabsorption syndrome.
• Known, existing uncontrolled coagulopathy.
• Any of the following laboratory values:
• Abnormal hematologic values (neutrophils [ANC]: <1.5 × 109/L, platelet count: <100 × 109/L)
• Impaired renal function (estimated creatinine clearance: <30 mL/min as calculated with Cockcroft-Gault equation). Note: In patients with moderate renal impairment (calculated creatinine clearance: 30 to 50 mL/min) at baseline, a dose reduction to (-1) of the capecitabine starting dose is required.
• Serum bilirubin >1.5 × upper normal limit (ULN).
• Alanine transaminase (ALT) or aspartate transaminase (AST) >2.5 × ULN (or >5 × ULN in the case of liver metastases).
• Alkaline phosphatase > 2.5 × ULN (or >5 × ULN in the case of liver metastases or >10 × ULN in the case of bone disease).
• International normalization ratio (INR) >1.6.
• History of:

• Bleeding diathesis,(ie, disseminated intravascular coagulation [DIC], clotting factor deficiency) or
• Long-term anticoagulant therapy,(other than antiplatelet therapy and warfarin 1 mg qd for port prophylaxis).
• History of hypersensitivity to active or inactive excipients of fulvestrant (ie, castor oil or Mannitol).
• Unwillingness to give written informed consent.
• Unwillingness to participate or inability to comply with the protocol for the duration of the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Accelerated Community Oncology Research Network

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lee S. Schwartzberg, MD

Role: PRINCIPAL_INVESTIGATOR

Acorn Cardiovascular, Inc.

Locations

Advanced Medical Specialties

Miami, Florida, United States

Northeast Georgia Cancer Care

Athens, Georgia, United States

Augusta Oncology Associates

Augusta, Georgia, United States

Medical & Surgical Specialists

Galesburg, Illinois, United States

Oncology Specialists

Park Ridge, Illinois, United States

Hematology Oncology Centers of the Northern Rockies

Billings, Montana, United States

Las Vegas Cancer Center

Henderson, Nevada, United States

The Lancaster Cancer Center, Ltd

Lancaster, Pennsylvania, United States

The West Clinic

Memphis, Tennessee, United States

Cancer Specialists of Tidewater

Chesapeake, Virginia, United States

Countries

United States

Other Identifiers

ALSSMBC0606

Identifier Type: -

Identifier Source: org_study_id