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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2007 by University of Southampton.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
University Hospital Southampton NHS Foundation Trust.
Information provided by (Responsible Party):
University of Southampton
ClinicalTrials.gov Identifier:
NCT00551122
First received: October 25, 2007
Last updated: January 22, 2013
Last verified: October 2007
  Purpose

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 Intervention 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

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Southampton:

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) [ 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 ]

Estimated Enrollment: 23
Study Start Date: November 2006
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   16 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00551122

Locations
United Kingdom
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust Recruiting
Birmingham, England, United Kingdom, B15 2TH
Contact: Michael H. Cullen, MD    0121-627-2444      
Southampton General Hospital Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: G. Mead, MD    44-23-8079-8639      
Royal Marsden - Surrey Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Robert A. Huddart, MD    44-20-8661-3457    robert.huddart@icr.ac.uk   
Sponsors and Collaborators
University of Southampton
University Hospital Southampton NHS Foundation Trust.
Investigators
Study Chair: G. Mead, MD University Hospital Southampton NHS Foundation Trust.
  More Information

Additional Information:
No publications provided

Responsible Party: University of Southampton
ClinicalTrials.gov Identifier: NCT00551122     History of Changes
Other Study ID Numbers: CDR0000572096, USCTU-UR1002-GEM-TIP, EU-20769, EUDRACT-2004-004804-19
Study First Received: October 25, 2007
Last Updated: January 22, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Southampton:
recurrent malignant testicular germ cell tumor
recurrent ovarian germ cell tumor
stage IV ovarian germ cell tumor
stage III malignant testicular germ cell tumor
testicular embryonal carcinoma and yolk sac tumor with seminoma
testicular yolk sac tumor and teratoma with seminoma
recurrent extragonadal non-seminomatous germ cell tumor
stage IV extragonadal non-seminomatous germ cell tumor
recurrent extragonadal germ cell tumor
ovarian mixed germ cell tumor
adult central nervous system germ cell tumor
testicular seminoma
testicular choriocarcinoma and seminoma
testicular embryonal carcinoma and seminoma
testicular embryonal carcinoma and teratoma with seminoma
recurrent extragonadal seminoma
stage IV extragonadal seminoma

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Germ Cell and Embryonal
Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Testicular Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Histologic Type
Genital Neoplasms, Male
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Nervous System Diseases
Genital Diseases, Male
Testicular Diseases
Paclitaxel
Gemcitabine
Isophosphamide mustard
Cisplatin
Ifosfamide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators

ClinicalTrials.gov processed this record on October 02, 2014