LY231514 Plus Gemcitabine in Treating Women With Metastatic Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Assess the antitumor activity of pemetrexed disodium 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. pemetrexed disodium 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.

Official Title
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A Phase II Study of a Combination of MTA (LY231514) and Gemcitabine in Patients With Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: pemetrexed disodium


Participation Criteria
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Eligibility Criteria
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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 pemetrexed disodium 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 pemetrexed disodium administration (5 days before for long acting agents such as naproxen, piroxicam, diflunisal, or nabumetone)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gemcitabine + pemetrexed<br>Patients receive gemcitabine IV over 30 minutes on days 1 and 8. pemetrexed disodium 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. | Drug: gemcitabine hydrochloride<br> <br> Drug: pemetrexed disodium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to progression |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV breast cancer, recurrent breast cancer