RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining LY231514 plus gemcitabine in treating women who have metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Drug: gemcitabine  Drug: pemetrexed disodium  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Assess the antitumor activity of LY231514 in combination with gemcitabine in the treatment of women with metastatic breast cancer who have received an anthracycline and a taxane in the adjuvant and/or metastatic setting and no more than 1 chemotherapy regimen for metastatic disease (unless these were a taxane and anthracycline).
• Determine the toxicity of this regimen in this patient population.
• Determine time to progression and overall survival of these patients receiving this regimen.

OUTLINE: Patients receive gemcitabine IV over 30 minutes on days 1 and 8. LY231514 IV is administered over 10 minutes 90 minutes following gemcitabine on day 8. Treatment continues every 21 days for a minimum of 6 courses in the absence of unacceptable toxicity or disease progression. Patients achieving a complete response receive 2 additional courses.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer with clinical evidence of metastatic disease
• Bidimensionally measurable disease
• If bisphosphonates used, must have measurable disease site other than bone
• No bone only disease
• Must have received a prior anthracycline and taxane in the adjuvant and/or metastatic setting
• No clinically significant pericardial effusions, pleural effusions, or ascites unless they can be drained
• No active CNS metastases
• Treated CNS metastasis that has ben stable for at least 8 weeks allowed
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST no greater than 3 times ULN (5 times ULN if liver metastases)
• Albumin at least 3.0 g/dL

Renal:

• Creatinine clearance at least 45 mL/min

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to take folic acid and cyanocobalamin (vitamin B12) supplements
• Body surface area less than 3 m^2
• No uncontrolled infection
• No chronic debilitating disease
• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated noninvasive carcinomas

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 4 weeks since prior immunotherapy
• At least 4 weeks since prior genetic therapy
• No concurrent immunomodulating agents

Chemotherapy:

• See Disease Characteristics
• No more than 3 prior chemotherapy regimens including adjuvant therapy
• No more than 1 prior chemotherapy regimen for metastatic disease unless these were a taxane and anthracycline
• At least 4 weeks since prior chemotherapy
• No prior gemcitabine and/or LY231514
• No other concurrent cytostatic or cytotoxic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to greater than 25% of bone marrow
• No prior strontium chloride Sr 89
• No concurrent radiotherapy

Surgery:

• At least 4 weeks since prior major surgery

Other:

• No aspirin or nonsteroidal antiinflammatory agents 2 days before, the day of, and for 2 days after LY231514 administration (5 days before for long acting agents such as naproxen, piroxicam, diflunisal, or nabumetone)

Arizona
      CCOP - Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
Florida
      Mayo Clinic, Jacksonville,  Florida,  32224,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
      Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
Michigan
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      CentraCare Health Plaza, Saint Cloud,  Minnesota,  56303,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States
North Dakota
      Altru Health Systems, Grand Forks,  North Dakota,  58201,  United States
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
      Medcenter One Health System, Bismarck,  North Dakota,  58501,  United States
Ohio
      CCOP - Toledo Community Hospital Oncology Program, Toledo,  Ohio,  43623-3456,  United States
Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States
Canada, Saskatchewan
      Allan Blair Cancer Centre, Regina,  Saskatchewan,  S4T 7T1,  Canada

Study chairs or principal investigators

Alex A. Adjei, MD, PhD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000068015; NCCTG-983253
Record last reviewed:  March 2003
Last Updated:  October 13, 2004
Record first received:  July 5, 2000
ClinicalTrials.gov Identifier:  NCT00006007
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08