Clinical trial NCT00227656: Capecitabine and Pegylated Interferon Alfa-2a in Treating Patients With Recurrent or Progressive Brain Metastases Due to Breast Cancer
Official title: Phase II Trial of Capecitabine (Xeloda®) and Pegylated Interferon Alfa-2A(Pegasys®) for Recurrent or Progressive Brain Metastasis From Breast Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Metastatic Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
male breast cancer
tumors metastatic to brain
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-09-28
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pegylated interferon alfa-2a may interfere with the growth of tumor cells. Giving capecitabine together with pegylated interferon alfa-2a may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving capecitabine together with pegylated interferon alfa-2a works in treating patients with recurrent or progressive brain metastases due to breast cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the efficacy of capecitabine and pegylated interferon alfa-2a, in terms of 6-month neurologic progression-free rate, in patients with recurrent or progressive brain metastases secondary to breast cancer.

Secondary

* Determine the toxicity spectrum of this regimen in these patients.
* Determine the time to neurologic progression and overall survival of patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral capecitabine twice daily on days 1-14 and pegylated interferon alfa-2a subcutaneously on days 1, 8, and 15. Treatment repeats every 3 weeks for at least 6 months in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 38-98 patients will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed breast cancer that metastasized to the brain, meeting all of the following criteria:

  * Must have ≥ 1 inoperable brain metastases, meeting 1 of the following criteria:

    * Progressive or recurrent disease after prior whole-brain or stereotactic radiotherapy
    * Ineligible for OR unwilling to be treated with radiotherapy
  * At least 1 unidimensionally measurable brain metastasis by enhanced MRI within the past 21 days
  * No progression or development of central nervous system (CNS) metastasis during prior treatment with capecitabine, fluorouracil, interferon alfa, or interferon beta
* Systemic (i.e., outside the CNS system) cancer must be stable

  * No progressive disease (e.g., liver, lymphangitic, or lung metastases)
* Hormone receptor status:

  * Not specified

PATIENT CHARACTERISTICS:

Age

* 18 and over

Sex

* Male or female

Menopausal status

* Not specified

Performance status

* Karnofsky 70-100%

Life expectancy

* More than 12 weeks

Hematopoietic

* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 10 mg/dL
* No history of idiopathic thrombocytopenic purpura
* No known uncontrolled coagulopathy
* No increased risk for anemia (e.g., thalassemia or spherocytosis)
* No medically problematic anemia

Hepatic

* aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤ 2.5 times upper limit of normal (ULN) (5 times ULN for patients with concurrent liver metastases )
* Bilirubin ≤ 1.5 times ULN
* Alkaline phosphatase ≤ 2.5 times ULN (5 times ULN for patients with concurrent liver metastases; 10 times ULN for patients with concurrent bone metastases)

Renal

* Creatinine ≤ 1.5 times ULN OR
* Creatinine clearance ≥ 30 mL/min

Cardiovascular

* No congestive heart failure
* No symptomatic coronary artery disease
* No medically uncontrolled arrhythmia
* No other clinically significant cardiac disease
* No myocardial infarction within the past 12 months

Gastrointestinal

* No history of inflammatory bowel disease
* Must have intact upper gastrointestinal tract
* Able to swallow tablets
* No malabsorption syndrome
* No history of gastrointestinal bleeding

Immunologic

* No prior unanticipated severe reaction to fluoropyrimidine therapy, interferon, pegylated interferon, or a pegylated moiety
* No known sensitivity to fluorouracil
* No serious uncontrolled infection
* No history of immunologically mediated disease

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 6 months after completion of study treatment
* No known dihydropyrimidine dehydrogenase deficiency
* No history of depression characterized by a suicide attempt
* No history of hospitalization for psychiatric disease
* No history of other severe psychiatric disease
* No prior disability as a result of psychiatric disease
* No history of clinically significant psychiatric disability that would preclude study compliance
* No other malignancy within the past 5 years except cured nonmelanoma skin cancer or treated carcinoma in situ of the cervix
* No uncontrolled thyroid dysfunction (e.g., thyroid-stimulating hormone not in normal range)
* No evidence of severe retinopathy (e.g., Cytomegalovirus (CMV) retinitis or macular degeneration)
* No clinically relevant ophthalmologic disorders due to diabetes or hypertension
* No other serious uncontrolled medical conditions that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics
* At least 3 months since prior interferon alfa or interferon beta

Chemotherapy

* See Disease Characteristics
* At least 3 months since prior capecitabine or fluorouracil

Endocrine therapy

* Concurrent hormonal agents (e.g., tamoxifen, raloxifene, or anastrazole) for breast cancer allowed

Radiotherapy

* See Disease Characteristics

Surgery

* More than 4 weeks since prior major surgery and recovered

Other

* More than 4 weeks since prior participation in another investigational drug study
* At least 4 weeks since prior and no concurrent brivudine or sorivudine
* No concurrent cimetidine
* No other concurrent investigational or commercial agents or therapies for this malignancy

Primary outcomes:
measure: Neurologic progression-free survival rate at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Time to neurologic progression
timeFrame: 6 months or until disease progression
measure: Overall survival
timeFrame: Up to 2 years
measure: Tumor response (complete response and partial response)
timeFrame: 6 months
measure: Toxicity
timeFrame: 6 months
Other outcomes:
Locations:
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids
state: Michigan
city: Springfield
country: United States
facility: Cancer Research for the Ozarks
state: Missouri
city: Houston
country: United States
facility: University of Texas M.D. Anderson CCOP Research Base
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Morris D. Groves, MD, JD
role: PRINCIPAL_INVESTIGATOR
References: