A Study of Pemetrexed and Cyclophosphamide Given Every 21 Days in Advanced Breast Cancer Patients

Study Overview
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Brief Summary
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This is the phase 2 portion of a phase 1/2 trial, testing the use of pemetrexed and cyclophosphamide in combination for the treatment of advanced breast cancer. A single arm Phase 1 dose finding (establish maximum tolerated dose) study precedes the randomized phase 2 portion.

Official Title
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A Phase 1/2 Dose-Escalating Study of ALIMTA and Cyclophosphamide Administered Every 21 Days in Patients With Locally Advanced or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: pemetrexed
* Drug: cyclophosphamide
* Drug: pemetrexed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - You must be female and at least 18 years old. - You must have been diagnosed with breast cancer. - Your pre-study lab tests are within study requirements. - You must be willing to take folic acid and vitamin B12. Exclusion Criteria: - You are pregnant or breastfeeding. - You have another illness that your doctor thinks would make you unable to participate. - You are currently taking aspirin or aspirin-like medicine and are unable to stop for a few days during each cycle of therapy.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pemetrexed 600 mg/m2<br> | Drug: pemetrexed<br>* Pemetrexed: 600 mg/m2, intravenous (IV), every 21 days x 8 cycles<br>* Other names: Alimta;Drug: cyclophosphamide<br>* 600 mg/m2, intravenous (IV), every 21 days x 8 cycles<br>|
| Experimental: Pemetrexed 1800 mg/m2<br> | Drug: cyclophosphamide<br>* 600 mg/m2, intravenous (IV), every 21 days x 8 cycles<br>Drug: pemetrexed<br>* 1800 mg/m2, intravenous (IV), every 21 days x 8 cycles<br>* Other names: Alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Tumor Response | Tumor response was assessed using radiological imaging, which was repeated every 6 weeks prior to every other cycle. Confirmation of response was to occur no less than 4 weeks (28 days) after the first evidence of response. | baseline to measured progressive disease | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progressive Disease | Time to progressive disease was defined as the time from the date of the first treatment dose to the first date of progressive disease or death from study disease. | baseline to measured progressive disease | 
| Progression Free Survival | Defined as date of first treatment dose to first date of progressive disease or death from any cause. For patients not known to have died as of data cutoff date and who did not have progressive disease, the progression free survival date was censored at last contact date. | baseline to measured progressive disease | 
| Pharmacokinetics - Maximum Observed Drug Concentration (Cmax) |  | cycle 1 (Day 1: <1 min prior to end of pemetrexed infusion; 1/2, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 hours after start of pemetrexed infusion) | 
| Pharmacokinetics - Area Under the Curve (AUC) | Area under the gemcitabine concentration-time curve from zero to last quantifiable concentration [AUC(0-t)] was calculated by combination of linear and logarithmic trapezoidal methods. Linear trapezoidal method was employed up to tmax (time to reach maximal concentration), and then log trapezoidal method was used for those data after tmax. | cycle 1 (Day 1: <1 min prior to end of pemetrexed infusion; 1/2, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 hours after start of pemetrexed infusion) | 
| Pharmacokinetics - Clearance (CL) | Total body clearance of drug calculated after intravenous administration. | cycle 1 (Day 1: <1 min prior to end of pemetrexed infusion; 1/2, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 hours after start of pemetrexed infusion) | 
| Pharmacokinetics - Volume of Distribution | Central volume (V1) and peripheral volume (V2) of distribution. | cycle 1 (Day 1: <1 min prior to end of pemetrexed infusion; 1/2, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 hours after start of pemetrexed infusion) | 
| Pharmacokinetics - Half-Life (t½) | The half-life associated with the terminal elimination rate constant. | cycle 1 (Day 1: <1 min prior to end of pemetrexed infusion; 1/2, 1, 1.5, 2, 3, 4, 6, 8, 24, 48, 72 hours after start of pemetrexed infusion) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Breast Cancer