Alimta® Plus Cisplatin & Paclitaxel Given Intraperitonelly; First Line Tx Stage III Ovarian Cancer
- Conditions
- Fallopian Tube CancerPeritoneal Cavity CancerOvarian Cancer
- Interventions
- Other: biologic sample preservation procedure
- Registration Number
- NCT00702299
- Lead Sponsor
- University of Arizona
- Brief Summary
RATIONALE: Pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed together with cisplatin and paclitaxel and giving them in different ways may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal pemetrexed when given together with intraperitoneal cisplatin and paclitaxel in treating patients with stage III ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer.
- Detailed Description
OBJECTIVES:
Primary
* To determine the maximum-tolerated dose (MTD) of combination therapy comprising intraperitoneal (IP) pemetrexed disodium in combination with IP cisplatin and paclitaxel in patients with optimally debulked stage III ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer in relation to the percentage of patients completing at least 6 courses of treatment.
* To determine the toxicity and the tolerability of this regimen in these patients.
Secondary
* To observe 80% of these patients progression free at 18 months after initiation of chemotherapy.
* To determine, as an exploratory endpoint, the median overall survival of patients treated with this regimen.
* To investigate the pharmacokinetics of this regimen at the determined MTD in these patients.
* To conduct correlative studies on tumor tissue and blood from these patients.
OUTLINE: This is a dose-escalation study of pemetrexed disodium.
Patients receive pemetrexed disodium intraperitoneally (IP) on day 1, cisplatin IP on day 2, and paclitaxel IP on day 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. At least 10 patients are treated at the maximum-tolerated dose (MTD).
Whole blood samples and tumor tissue specimens are obtained from patients at baseline and banked for future DNA, RNA, and protein studies related to prediction of disease progression and treatment resistance. Plasma and intraperitoneal fluid samples may also be collected from patients treated at the MTD for pharmacokinetic analysis of plasma concentrations of pemetrexed disodium by high-performance liquid chromatography (HPLC) or mass spectrometry-HPLC.
After completion of study therapy, patients are followed periodically.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Receiving Treatment biologic sample preservation procedure Dose escalation of day 1 i.p. pemetrexed disodium accrued three patients to each of five dose levels (60-1,000 mg/m2), along with day 2 i.p. cisplatin (75 mg/m2) and day 8 i.p. paclitaxel (60 mg/m2) with a biologic sample preservation procedure Receiving Treatment pemetrexed disodium Dose escalation of day 1 i.p. pemetrexed disodium accrued three patients to each of five dose levels (60-1,000 mg/m2), along with day 2 i.p. cisplatin (75 mg/m2) and day 8 i.p. paclitaxel (60 mg/m2) with a biologic sample preservation procedure Receiving Treatment cisplatin Dose escalation of day 1 i.p. pemetrexed disodium accrued three patients to each of five dose levels (60-1,000 mg/m2), along with day 2 i.p. cisplatin (75 mg/m2) and day 8 i.p. paclitaxel (60 mg/m2) with a biologic sample preservation procedure Receiving Treatment paclitaxel Dose escalation of day 1 i.p. pemetrexed disodium accrued three patients to each of five dose levels (60-1,000 mg/m2), along with day 2 i.p. cisplatin (75 mg/m2) and day 8 i.p. paclitaxel (60 mg/m2) with a biologic sample preservation procedure
- Primary Outcome Measures
Name Time Method Maximum-tolerated Dose of Pemetrexed With a Day 2 i.p. Cisplatin (75 mg/m2) and Day 8 i.p. Paclitaxel (60 mg/m2) 18 months If none of the initial 3 patients on a dose level experienced a dose-limiting toxicity (DLT) after the first cycle of therapy, then the dose was escalated to the next level. If 2 or more patients on any dose level experienced a DLT, then the maximum tolerated dose would be determined to be the next lower dose level.
Patients That Completed at Least 6 Courses of Therapy of Pemetrexed Along With Day 2 i.p. Cisplatin (75 mg/m2) and Day 8 i.p. Paclitaxel (60 mg/m2)at the Determined Maximum Tolerated Dose 18 months If none of the initial 3 patients on a dose level experienced a dose-limiting toxicity (DLT) after the first cycle of therapy, then the dose was escalated to the next level. If 2 or more patients on any dose level experienced a DLT, then the Maximum Tolerance Dose (MTD) would be determined to be the next lower dose level.
Patients Experienced Grade >=3 Toxicity at Dose Level 5 (1,000 mg/m2 IP Pemetrexed) 18 months Toxicity was assessed by NCI Common Toxicity Criteria for Adverse Effects v3.0
- Secondary Outcome Measures
Name Time Method Progression-free Survival at 18 Months as Assessed by Cancer Antigen 125 18 months Progression was evaluated with posttreatment CT scans and measured changes in cancer antigen 125 levels 6 months after the initiation of the treatment regimen, or within one month after discontinuation of treatment if stopped early. Cancer antigen 125 response in evaluable patients (N=13) was analyzed using the modified Gynecologic Cancer Intergroup (GCIG) criteria. There was one evaluable patient by Response Evaluation Criteria in Solid Tumors(RECIST) criteria
Overall Survival Average Length of follow-up 788 days Pharmacokinetics (Mean Cmax, ug/mL)for Different Dosages of Pemetrexed 18 months Cmax levels were found through plasma collected between 0.5 to 4 hours and at 24 hours after initiation of intraperitoneal administration
Trial Locations
- Locations (2)
Arizona Oncology - Scottsdale
🇺🇸Scottsdale, Arizona, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States