Gemcitabine, Paclitaxel, Ifosfamide, and Cisplatin in Treating Patients With Progressive or Relapsed Metastatic Germ Cell Tumors (GemTIP)
Recruitment status was: Recruiting
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, paclitaxel, ifosfamide, and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of gemcitabine when given together with paclitaxel, ifosfamide, and cisplatin, and to see how well they work in treating patients with progressive or relapsed metastatic germ cell tumors.
Brain and Central Nervous System Tumors
Extragonadal Germ Cell Tumor
Testicular Germ Cell Tumor
Drug: gemcitabine hydrochloride
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Multicentre Trial of Salvage Chemotherapy With Gem-TIP for Relapsed Germ Cell Cancer|
- Maximum tolerated dose of gemcitabine hydrochloride when administered with TIP chemotherapy comprising paclitaxel, ifosfamide, and cisplatin with growth factor support (phase I) [ Time Frame: end of study ] [ Designated as safety issue: Yes ]
- Response rates (phase I) [ Time Frame: end of study ] [ Designated as safety issue: No ]
- Failure-free survival (phase I) [ Time Frame: end of study ] [ Designated as safety issue: No ]
- Utility of positron emission tomography scanning after Gem-TIP chemotherapy (phase I) [ Time Frame: end of study ] [ Designated as safety issue: No ]
- Degree of dose intensification achieved with Gem-TIP chemotherapy relative to a previous Medical Research Council study with TIP alone (phase II) [ Time Frame: end of study ] [ Designated as safety issue: No ]
|Study Start Date:||November 2006|
|Estimated Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Experimental: Paclitaxel, gemcitabine, cisplatin, ifosfamide
Day 1 Dexamethasone sodium phosphate 25mg I/V ) before Chlorphenamine 10mg I/V 30 - 60 mins ) paclitaxel Ranitidine 50mg I/V ) Paclitaxel - 175 mg m2 I/V in 500ml normal saline over 3 hours Gemcitabine - 1200mg per m2 I/V in 500ml normal saline over 30 mins Days 1-5 Cisplatin 20mg per m2 in 1 litre normal saline over 4 hours 2 litres normal saline over 16 hours, each litre containing 10 mmol MgSO4 and 20mmol KCL.
If urine output is insufficient (less than 600ml per 6 hours) or if excessive weight gain (greater than 2kg) 100 - 200ml 10% mannitol should be used. Alternatively, low dose frusemide (20mg I/V) can be used.
Days 2 - 6 Ifosfamide 1G per m2 + MESNA 0.5G m2 in 500 ml normal saline over 1 hour after the cisplatin infusion.
MESNA 0.5G m2 to be included in first 1 litre post cisplatin hydration bag Pegylated G-CSF will be given on day 7 as an alternative to daily G-CSF.
|Biological: filgrastim Biological: lenograstim Biological: pegfilgrastim Drug: cisplatin Drug: gemcitabine hydrochloride Drug: ifosfamide Drug: paclitaxel|
- To determine the maximum tolerated dose (MTD) of gemcitabine hydrochloride when administered with TIP chemotherapy comprising paclitaxel, ifosfamide, and cisplatin with growth factor support (Gem-TIP) in patients with progressive or relapsed metastatic germ cell tumors.
- To compare the MTD of the Gem-TIP regimen with the MTD determined in a previous Medical Research Council study of TIP alone.
- To compare the degree of dose intensification achieved with Gem-TIP chemotherapy with that achieved in the prior study of TIP chemotherapy alone.
- To assess the dose of gemcitabine hydrochloride that can be delivered with the TIP regimen in these patients.
- To measure response rates and failure-free survival of patients treated with Gem-TIP alone.
- To assess the utility of PET scanning after Gem-TIP chemotherapy in these patients.
OUTLINE: This is a multicenter, phase I dose-escalation study of gemcitabine hydrochloride followed by a phase II study.
- Phase I: Patients receive gemcitabine hydrochloride IV over 30 minutes and paclitaxel IV over 3 hours on day 1, cisplatin IV over 4 hours on days 1-5, and ifosfamide IV over 1 hour on days 2-6. Patients also receive filgrastim or lenograstim (G-CSF) subcutaneously (SC) on days 7-18 or until blood counts recover OR pegfilgrastim SC once on day 6. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Phase II: An additional cohort of 14 patients is treated as in phase I at the MTD determined in phase I.
After completion of study therapy, patients are followed periodically for up to 1 year and then at the investigator's discretion.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00551122
|Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust|
|Birmingham, England, United Kingdom, B15 2TH|
|Southampton General Hospital|
|Southampton, England, United Kingdom, SO16 6YD|
|Royal Marsden - Surrey|
|Sutton, England, United Kingdom, SM2 5PT|
|Study Chair:||G. Mead, MD||University Hospital Southampton NHS Foundation Trust|