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

NCT ID: NCT00551122

Last Updated: 2013-01-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30

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.

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.

Conditions

Brain and Central Nervous System Tumors; Extragonadal Germ Cell Tumor; Ovarian Cancer; Testicular Germ Cell Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

lenograstim

Intervention Type: BIOLOGICAL

pegfilgrastim

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

Interventions

filgrastim

Intervention Type: BIOLOGICAL

lenograstim

Intervention Type: BIOLOGICAL

pegfilgrastim

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role: collaborator

University of Southampton

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

G. Mead, MD

Role: STUDY_CHAIR

University Hospital Southampton NHS Foundation Trust

Locations

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham, England, United Kingdom

Site Status: RECRUITING

Southampton General Hospital

Southampton, England, United Kingdom

Site Status: RECRUITING

Royal Marsden - Surrey

Sutton, England, United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Facility Contacts

Michael H. Cullen, MD

Role: primary

0121-627-2444

G. Mead, MD

Role: primary

44-23-8079-8639

Robert A. Huddart, MD

Role: primary

robert.huddart@icr.ac.uk

44-20-8661-3457

Other Identifiers

USCTU-UR1002-GEM-TIP

Identifier Type: -

Identifier Source: secondary_id

EU-20769

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2004-004804-19

Identifier Type: -

Identifier Source: secondary_id

CDR0000572096

Identifier Type: -

Identifier Source: org_study_id