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

January 22, 2013 updated by: University of Southampton

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

23

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • England
      • Birmingham, England, United Kingdom, B15 2TH
        • Recruiting
        • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
        • Contact:
          • Michael H. Cullen, MD
          • Phone Number: 0121-627-2444
      • Southampton, England, United Kingdom, SO16 6YD
        • Recruiting
        • Southampton General Hospital
        • Contact:
          • G. Mead, MD
          • Phone Number: 44-23-8079-8639
      • Sutton, England, United Kingdom, SM2 5PT
        • Recruiting
        • Royal Marsden - Surrey

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 60 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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.
Drug: cisplatin
Drug: gemcitabine hydrochloride
Drug: paclitaxel
Biological: filgrastim
Drug: ifosfamide
Biological: pegfilgrastim
Biological: lenograstim

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
end of study
Response rates (phase I)
Time Frame: end of study
end of study
Failure-free survival (phase I)
Time Frame: end of study
end of study
Utility of positron emission tomography scanning after Gem-TIP chemotherapy (phase I)
Time Frame: end of study
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)
Time Frame: end of study
end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Southampton

Collaborators

University Hospital Southampton NHS Foundation Trust

Investigators

  • Study Chair: G. Mead, MD, University Hospital Southampton NHS Foundation Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (ANTICIPATED)

April 1, 2013

Study Registration Dates

First Submitted

October 25, 2007

First Submitted That Met QC Criteria

October 25, 2007

First Posted (ESTIMATE)

October 30, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

January 23, 2013

Last Update Submitted That Met QC Criteria

January 22, 2013

Last Verified

October 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000572096
  • USCTU-UR1002-GEM-TIP
  • EU-20769
  • EUDRACT-2004-004804-19

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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