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

Ovarian Cancer Clinical Trial

— GemTIP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00551122
• Other study ID #: CDR0000572096
• Secondary ID: USCTU-UR1002-GEM
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: October 25, 2007
• Last updated: January 22, 2013
• Start date: November 2006

Study information

• Verified date: October 2007
• Source: University of Southampton
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 23
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 60 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Extragonadal Germ Cell Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Nervous System Neoplasms
• Ovarian Cancer
• Testicular Germ Cell Tumor
• Testicular Neoplasms

Intervention

Biological:
• filgrastim

• lenograstim

• pegfilgrastim

Drug:
• cisplatin

• gemcitabine hydrochloride

• ifosfamide

• paclitaxel

Locations

Country	Name	City	State
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (2)

Lead Sponsor	Collaborator
University of Southampton	University Hospital Southampton NHS Foundation Trust.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	Response rates (phase I)		end of study	No
Primary	Failure-free survival (phase I)		end of study	No
Primary	Utility of positron emission tomography scanning after Gem-TIP chemotherapy (phase I)		end of study	No
Primary	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	No