Intraperitoneal Pemetrexed, Cisplatin, and Paclitaxel as First-Line Therapy in Treating Women With Stage III Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer
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.
Fallopian Tube Cancer
Peritoneal Cavity Cancer
Drug: pemetrexed disodium
Other: biologic sample preservation procedure
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Open Label Trial of Alimta® Plus Cisplatin and Paclitaxel Given Intraperitoneally (IP) as First Line Treatment for Women With Stage III Ovarian Cancer|
- Maximum-tolerated Dose of Pemetrexed With a Day 2 i.p. Cisplatin (75 mg/m2) and Day 8 i.p. Paclitaxel (60 mg/m2) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]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 [ Time Frame: 18 months ] [ Designated as safety issue: No ]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 That Experienced Grade >=3 Toxicity at Dose Level 5 (1,000 mg/m2 i.p. Pemetrexed) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]Toxicity was assessed by NCI Common Toxicity Criteria for Adverse Effects v3.0
- Progression-free Survival at 18 Months as Assessed by Cancer Antigen 125 [ Time Frame: 18 months ] [ Designated as safety issue: No ]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 [ Time Frame: Average Length of follow-up 788 days ] [ Designated as safety issue: No ]
- Pharmacokinetics (Mean Cmax, ug/mL)for Different Dosages of Pemetrexed [ Time Frame: 18 months ] [ Designated as safety issue: No ]Cmax levels were found through plasma collected between 0.5 to 4 hours and at 24 hours after initiation of intraperitoneal administration
|Study Start Date:||September 2007|
|Study Completion Date:||October 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Experimental: Receiving Treatment
Dose escalation of day 1 i.p. pemetrexed 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)
IP cisplatin will be administered on day 2 of each cycle at 75mg per m2 and IP paclitaxel will be administered at 60mg per m2 on day 8 of each cycle. Courses will be repeated every 21 days for up to 6 cyclesDrug: paclitaxel
IP cisplatin will be administered on day 2 of each cycle at 75mg per m2 and IP paclitaxel will be administered at 60mg per m2 on day 8 of each cycle. Courses will be repeated every 21 days for up to 6 cyclesDrug: pemetrexed disodium
Escalate doses in groups of 3 patients to 60mg per m2, 120 mg per m2, 500 mg per m2, 750 mg per m2, 1000 mg per m2
Other Name: AlimtaOther: biologic sample preservation procedure
Plasma samples will be collected on the 1st course at baseline, 30 minutes, 60 minutes, 2 hours, 4 hours, 6 hours (if possible) and 24 hours after the first IP Alimta® dose.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00702299
|United States, Arizona|
|Arizona Oncology - Scottsdale|
|Scottsdale, Arizona, United States, 85258|
|Arizona Cancer Center at University of Arizona Health Sciences Center|
|Tucson, Arizona, United States, 85724-5024|
|Study Chair:||Setsuko K. Chambers, MD||University of Arizona|
|Principal Investigator:||David S. Alberts, MD||University of Arizona|