S0430 Cyclophosphamide and Capecitabine in Treating Women With Stage IV Breast Cancer

Phase II Trial of Simple Oral Therapy (Continuous Oral Cyclophosphamide and Capecitabine) in Patients With Metastatic Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one chemotherapy drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cyclophosphamide together with capecitabine works in treating women with stage IV breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: capecitabine

Detailed Description

OBJECTIVES:

• Determine the response rate (complete and partial, confirmed and unconfirmed) in women with stage IV breast cancer treated with oral cyclophosphamide and oral capecitabine.
• Determine the progression-free survival and overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral cyclophosphamide once daily on days 1-14 and oral capecitabine twice daily on days 8-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then at weeks 7, 13, 19, and 25.

After completion of study treatment, patients are followed every 3 months for up to 2 years.

PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study within 4 years.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Cancer Center
    • Anchorage, Alaska, United States, 99508
      • Alaska Regional Hospital Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Castro Valley, California, United States, 94546
      • Eden Medical Center
    • Fremont, California, United States, 94538
      • Kaiser Permanente - Fremont
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Hayward, California, United States, 94545
      • Kaiser Permanente Medical Center - Hayward
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94602
      • Highland General Hospital
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94611
      • Kaiser Permanente Medical Center - Oakland
    • Pleasanton, California, United States, 94588
      • Valley Care Medical Center
    • Redwood City, California, United States, 94063
      • Kaiser Permanente Medical Center - Redwood City
    • Richmond, California, United States, 94801
      • Kaiser Permanente Medical Center - Richmond
    • Roseville, California, United States, 95661
      • Kaiser Permanente Medical Center - Roseville
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Sacramento, California, United States, 95823
      • South Sacramento Kaiser-Permanente Medical Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Center - Sacramento
    • San Francisco, California, United States, 94115
      • Kaiser Permanente Medical Center - San Francisco Geary Campus
    • San Jose, California, United States, 95119
      • Kaiser Permanente Medical Center - Santa Teresa
    • San Pablo, California, United States, 94806
      • Doctors Medical Center - San Pablo Campus
    • San Rafael, California, United States, 94903
      • Kaiser Foundation Hospital - San Rafael
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara Kiely Campus
    • Santa Rosa, California, United States, 95403
      • Kaiser Permanente Medical Center - Santa Rosa
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente Medical Center - South San Francisco
    • Stockton, California, United States, 95210
      • Kaiser Permanente Medical Facility - Stockton
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Medical Center - Vallejo
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente Medical Center - Walnut Creek
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center at UC Health Sciences Center
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center
    • Edwards, Colorado, United States, 81632
      • Shaw Cancer Center at Vail Valley Medical Center
  • Georgia
    • Savannah, Georgia, United States, 31403-3089
      • Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
    • Valdosta, Georgia, United States, 31603
      • Pearlman Comprehensive Cancer Center at South Georgia Medical Center
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Hospital at Saint Anthony's Health Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Mt. Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Naperville, Illinois, United States, 60540
      • Edward Hospital Cancer Center
    • Springfield, Illinois, United States, 62781-0001
      • Regional Cancer Center at Memorial Medical Center
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Kansas City, Kansas, United States, 66160-7357
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - Salina
    • Salina, Kansas, United States, 67401
      • Tammy Walker Cancer Center at Salina Regional Health Center
    • Topeka, Kansas, United States, 66606
      • St. Francis Comprehensive Cancer Center
    • Topeka, Kansas, United States, 66604
      • Cotton-O'Neil Cancer Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67203
      • Associates in Womens Health, PA - North Review
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • Caritas Holy Family Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0942
      • University of Michigan Comprehensive Cancer Center
    • Lansing, Michigan, United States, 48910
      • Breslin Cancer Center at Ingham Regional Medical Center
    • Mount Clemens, Michigan, United States, 48043
      • Ted B. Wahby Cancer Center at Mount Clemens General Hospital
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Gape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
    • Springfield, Missouri, United States, 65802
      • CCOP - Cancer Research for the Ozarks
    • Springfield, Missouri, United States, 65804
      • St. John's Regional Health Center
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
    • St. Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405
    • Great Falls, Montana, United States, 59405-5309
      • Big Sky Oncology
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology at KRMC
    • Missoula, Montana, United States, 59801
      • Community Medical Center
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • New York
    • Glens Falls, New York, United States, 12801
      • Adirondack Cancer Care - Glens Falls
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Independence, Ohio, United States, 44131
      • Community Oncology Group at Cleveland Clinic Cancer Center
    • Mansfield, Ohio, United States, 44903
      • MedCentral - Mansfield Hospital
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic - Wooster
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Portland, Oregon, United States, 97213-2967
      • Providence Cancer Center at Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center & Children's Hospital
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis Cancer Center at Roper Hospital
  • Texas
    • El Paso, Texas, United States, 79902
      • Center for Cancer Medicine and Blood Disorders, PA
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Cedar City, Utah, United States, 84720
      • Sandra L. Maxwell Cancer Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Murray, Utah, United States, 84157
      • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
    • Salt Lake City, Utah, United States, 84103
      • Latter Day Saints Hospital
  • Washington
    • Auburn, Washington, United States, 98002
      • Auburn Regional Center for Cancer Care
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Centralia, Washington, United States, 98531-9027
      • Providence Centralia Hospital
    • Federal Way, Washington, United States, 98003
      • St. Francis Hospital
    • Mt. Vernon, Washington, United States, 98273
      • Skagit Valley Hospital Cancer Care Center
    • Olympia, Washington, United States, 98506-5166
      • Providence St. Peter Hospital Regional Cancer Center
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Cancer Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical, PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98122
      • Polyclinic First Hill
    • Seattle, Washington, United States, 98195-6043
      • University Cancer Center at University of Washington Medical Center
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Tacoma, Washington, United States, 98405
      • Allenmore Hospital
    • Tacoma, Washington, United States, 98405
      • CCOP - Northwest
    • Tacoma, Washington, United States, 98405
      • MultiCare Regional Cancer Center at Tacoma General Hospital
    • Tacoma, Washington, United States, 98499
      • St. Clare Hospital
    • Tacoma, Washington, United States, 98405-3004
      • St. Joseph Medical Center at Franciscan Health System
    • Vancouver, Washington, United States, 98668
      • Southwest Washington Medical Center Cancer Center
    • Wenatchee, Washington, United States, 98801-2028
      • Wenatchee Valley Medical Center
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • United Hospital Center
    • Parkersburg, West Virginia, United States, 26102
      • Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed stage IV breast cancer

  • Metastatic disease (M1) OR multiple sites of new disease that is clinically obvious metastatic disease (i.e., multiple sites of new osseous disease)

• Meets 1 of the following criteria:

  • Measurable disease

  • Non-measurable disease

    • MUC-1 antigen level > 2 times upper limit of normal AND level has increased by 1.5 times

• Must have documented MUC-1 antigen level

  • Either cancer antigen (CA) 15-3 or CA 27-29 allowed
• Must have received at least 1 prior hormonal therapy for metastatic disease (estogen receptor-positive patients only)

• No symptomatic brain or CNS metastases

  • Previously treated brain or CNS metastasis allowed provided radiotherapy was completed ≥ 8 weeks before study entry

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• No known existing uncontrolled coagulopathy

Hepatic

• Not specified

Renal

• Creatinine clearance > 40 mL/min

Cardiovascular

• No congestive heart failure
• No symptomatic coronary artery disease
• No cardiac arrhythmia not well controlled with medication
• No myocardial infarction within the past 12 months
• No other clinically significant cardiac disease

Gastrointestinal

• Able to take oral medication
• No uncontrolled nausea, vomiting, or diarrhea
• No lack of physical integrity of the upper gastrointestinal tract
• No malabsorption syndrome

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No active infection requiring systemic therapy
• No prior severe reaction to fluoropyrimidines
• No known sensitivity to fluorouracil
• No known dihydropyrimidine dehydrogenase deficiency
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy or biologic therapy for breast cancer
• No concurrent gene therapy for breast cancer
• No concurrent filgrastim (G-CSF)

Chemotherapy

• At least 14 days since prior chemotherapy and recovered
• No more than 2 prior chemotherapy regimens for metastatic disease
• No prior capecitabine for metastatic disease

• No prior oral cyclophosphamide for metastatic disease

  • Prior IV cyclophosphamide allowed
• No other concurrent chemotherapy for breast cancer

Endocrine therapy

• See Disease Characteristics
• No concurrent hormonal therapy for breast cancer

Radiotherapy

• See Disease Characteristics
• At least 14 days since prior radiotherapy to non-CNS disease sites and recovered
• No concurrent radiotherapy for breast cancer

Surgery

• Not specified

Other

• Concurrent bisphosphonates allowed

• No concurrent full-dose warfarin

  • Concurrent prophylactic warfarin (≤ 1 mg/day) to maintain port patency allowed
• No other concurrent antineoplastic therapy for breast cancer

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: cyclophosphamide and capecitabine; cyclophosphamide orally days 1-14 and capecitabine orally days 15-21 for 8 cycles of 21 days each	Drug: cyclophosphamide; Other Names: cytoxan; Drug: capecitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (Complete and Partial, Confirmed and Unconfirmed)	Complete Response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms. Normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.	Patients assessed at least every six weeks while on protocol treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival and Overall Survival	Progression-Free Survival: From date of registration to time of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at last date of contact. Overall Survival: From date of registration to date of death due to any cause. Patients last known to be alive are censored at last date of contact. Progression is 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed and/or unequivocal progression of non-measurable disease and/or appearance of new lesion/site or death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.	two years
Toxicity	Number of patients for whom Grade 3 or higher toxicity observed during treatment. Only adverse events that are possibly, probably or definitely related to study drug are reported.	Patients assessed after each 21-day cycle for 8 cycles (24 weeks of treatment)

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: April 5, 2005
• First Submitted That Met QC Criteria: April 5, 2005
• First Posted (Estimate): April 6, 2005

Study Record Updates

• Last Update Posted (Estimate): July 18, 2013
• Last Update Submitted That Met QC Criteria: July 3, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Capecitabine
• Other Study ID Numbers: CDR0000423180; U10CA032102 (U.S. NIH Grant/Contract); S0430 (Other Identifier: SWOG)