GemTIP: Gemcitabine, Paclitaxel, Ifosfamide, and Cisplatin in Treating Patients With Progressive or Relapsed Metastatic Germ Cell Tumors

Sponsor

University of Southampton (Other)

Overall Status

Unknown status

CT.gov ID

NCT00551122

Collaborator

University Hospital Southampton NHS Foundation Trust (Other)

Enrollment

Locations

Arm

7.7

Patients Per Site

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Extragonadal Germ Cell Tumor Ovarian Cancer Testicular Germ Cell Tumor	Biological: filgrastim Biological: lenograstim Biological: pegfilgrastim Drug: cisplatin Drug: gemcitabine hydrochloride Drug: ifosfamide Drug: paclitaxel	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

23 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I/II Multicentre Trial of Salvage Chemotherapy With Gem-TIP for Relapsed Germ Cell Cancer

Study Start Date :

Nov 1, 2006

Anticipated Primary Completion Date :

Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of gemcitabine hydrochloride when administered with TIP chemotherapy comprising paclitaxel, ifosfamide, and cisplatin with growth factor support (phase I) [end of study]
Response rates (phase I) [end of study]
Failure-free survival (phase I) [end of study]
Utility of positron emission tomography scanning after Gem-TIP chemotherapy (phase I) [end of study]
Degree of dose intensification achieved with Gem-TIP chemotherapy relative to a previous Medical Research Council study with TIP alone (phase II) [end of study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Meets the following criteria:
Histologically confirmed extracranial primary germ cell cancer, seminoma, or nonseminoma
Unresectable metastatic disease
No completely resected cancer
Rising serum markers (i.e., alpha-fetoprotein and human chorionic gonadotropin) on sequential measurement or biopsy-proven unresectable germ cell cancer
In first relapse after a single prior cisplatin-containing combination chemotherapy
Patients with late relapse (i.e., > 2 years post initial chemotherapy) should be considered for surgery rather than chemotherapy, if technically feasible
No patients with cerebral metastases alone
Progressive cerebral and systemic disease may be considered for this study, provided cranial irradiation is also considered as a component of care

PATIENT CHARACTERISTICS:

Medically and psychologically fit to receive this intensive chemotherapy schedule
WBC > 3.5 times 10^9/L
Platelet count > 130 times 10^9/L
Glomerular filtration rate ≥ 50 mL/min (as determined by 24 hour creatinine clearance or nuclear medicine technique)
Fertile patients must use effective contraception
No other prior malignancy except successfully treated nonmelanoma skin cancer or superficial bladder cancer
No prior allergic reactions to cisplatin or other platinum compounds

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England	United Kingdom	B15 2TH
2	Southampton General Hospital	Southampton	England	United Kingdom	SO16 6YD
3	Royal Marsden - Surrey	Sutton	England	United Kingdom	SM2 5PT