Clinical trial NCT00006007: LY231514 Plus Gemcitabine in Treating Women With Metastatic Breast Cancer
Official title: A Phase II Study of a Combination of MTA (LY231514) and Gemcitabine in Patients With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IV breast cancer
recurrent breast cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 59
Sex: FEMALE
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 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: 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.

Eligibility 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 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)

Primary outcomes:
measure: time to progression
timeFrame: Up to 5 years
Secondary outcomes:
measure: overall survival
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Scottsdale Oncology Program
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Illinois Oncology Research Association
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Ann Arbor
country: United States
facility: CCOP - Ann Arbor Regional
state: Michigan
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Health Plaza
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Bismarck
country: United States
facility: Medcenter One Health System
state: North Dakota
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Health Systems
state: North Dakota
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital Oncology Program
state: Ohio
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Mayo Clinic
name: Alex A. Adjei, MD, PhD
role: STUDY_CHAIR
References:
citation: Ma CX, Steen P, Rowland KM, Niedringhaus RD, Fitch TR, Kugler JW, Hillman DW, Perez EA, Ingle JN, Adjei AA. A phase II trial of a combination of pemetrexed and gemcitabine in patients with metastatic breast cancer: an NCCTG study. Ann Oncol. 2006 Feb;17(2):226-31. doi: 10.1093/annonc/mdj054. Epub 2005 Nov 22.
citation: Ma CX, Steen P, Rowland KM, et al.: A phase II study of a combination of pemetrexed (Pem) and gemcitabine (Gem) in patients with metastatic breast cancer (MBC): an NCCTG study. [Abstract] J Clin Oncol 22 (Suppl 14): A-639, 36s, 2004.