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

NCT00534417 | Completed Phase 2 Results

• 1 other identifier: ALSSMBC0606
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 10

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

Keywords

Hormone; Receptor; Positive; Metastatic; Breast; Cancer

Outcome Measures

Primary Outcomes (2)

• Time to Progression (TTP)

  Time to progression is defined as the time from treatment start until objective tumor progression. Progression is defined per Response Evaluation Criteria in Solid Tumors (RECIST)v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions. The median time to progression is the parameter used to describe TTP.

  TTP was measured from day 1 of treatment until time of progression (assessed every 8 weeks), up to 29 months.

• Progression-free Survival (PFS)

  Disease progression was determined through radiology imaging measurements and by clinical or symptomatic progression during or after treatment. Progression is defined per RECIST v1.0 guidelines as a measurable increase in the smallest diameter of any target lesion, progression of existing non-target lesions, or the appearance of 1 or more new lesions.

  PFS was measured from day 1 of treatment until time of progression (assessed every 8 weeks) or death, whichever came first, up to 32.5 months.

Secondary Outcomes (6)

• Best Overall Response

  Response to treatment was assessed after every 8 weeks of treatment

• Overall Response Rate

  Response to treatment was assessed after every 8 weeks of treatment

• Clinical Benefit Rate

  Response to treatment was assessed after every 8 weeks of treatment

• Patients Experiencing Severe Symptom Burden (Physical Symptoms)

  The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.

• Patients Experiencing Severe Symptom Burden (Psychiatric Symptoms)

  The questionnaire was administered on day 1 of every cycle (approximately every 4 weeks) during study treatment.

Study Arms (1)

Capecitabine and fulvestrant

EXPERIMENTAL

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.

Drug: capecitabine; Drug: fulvestrant

Interventions

capecitabine 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.

Also known as: Xeloda

Capecitabine and fulvestrant

fulvestrant 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).

Also known as: Faslodex

Capecitabine and fulvestrant

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Accelerated Community Oncology Research Network: lead
• Hoffmann-La Roche: collaborator
• AstraZeneca: collaborator

Study Sites (10)

Advanced Medical Specialties

Miami, Florida, 33176, United States

Location

Northeast Georgia Cancer Care

Athens, Georgia, 30607, United States

Location

Augusta Oncology Associates

Augusta, Georgia, 30901, United States

Location

Medical & Surgical Specialists

Galesburg, Illinois, 61401, United States

Location

Oncology Specialists

Park Ridge, Illinois, 60068, United States

Location

Hematology Oncology Centers of the Northern Rockies

Billings, Montana, 59101, United States

Location

Las Vegas Cancer Center

Henderson, Nevada, 89052, United States

Location

The Lancaster Cancer Center, Ltd

Lancaster, Pennsylvania, 17605, United States

Location

The West Clinic

Memphis, Tennessee, 38120, United States

Location

Cancer Specialists of Tidewater

Chesapeake, Virginia, 23320, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

Capecitabine; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Vice President of Scientific Affairs
• Organization: Accelerated Community Oncology Research Network, Inc.

mwalker@acorncro.com

901-435-5570

Study Officials

• Lee S. Schwartzberg, MD

  Acorn Cardiovascular, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2007
• First Posted: September 24, 2007
• Study Start: October 1, 2007
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: February 1, 2013
• Results First Posted: February 1, 2013

Record last verified: 2012-12

Locations

US (10)