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

Primary Purpose

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

Status
Unknown status
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
filgrastim
lenograstim
pegfilgrastim
cisplatin
gemcitabine hydrochloride
ifosfamide
paclitaxel
Sponsored by
University of Southampton
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring recurrent malignant testicular germ cell tumor, testicular seminoma, recurrent ovarian germ cell tumor, stage IV ovarian germ cell tumor, stage III malignant testicular germ cell tumor, testicular choriocarcinoma and seminoma, testicular embryonal carcinoma and seminoma, testicular embryonal carcinoma and teratoma with seminoma, testicular embryonal carcinoma and yolk sac tumor with seminoma, testicular yolk sac tumor and teratoma with seminoma, recurrent extragonadal non-seminomatous germ cell tumor, recurrent extragonadal seminoma, stage IV extragonadal non-seminomatous germ cell tumor, stage IV extragonadal seminoma, recurrent extragonadal germ cell tumor, ovarian mixed germ cell tumor, adult central nervous system germ cell tumor

Eligibility Criteria

16 Years - 60 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Queen Elizabeth Hospital at University Hospital of Birmingham NHS TrustRecruiting
  • Southampton General HospitalRecruiting
  • Royal Marsden - SurreyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Paclitaxel, gemcitabine, cisplatin, ifosfamide

Arm Description

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.

Outcomes

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)
Response rates (phase I)
Failure-free survival (phase I)
Utility of positron emission tomography scanning after Gem-TIP chemotherapy (phase I)
Degree of dose intensification achieved with Gem-TIP chemotherapy relative to a previous Medical Research Council study with TIP alone (phase II)

Secondary Outcome Measures

Full Information

First Posted
October 25, 2007
Last Updated
January 22, 2013
Sponsor
University of Southampton
Collaborators
University Hospital Southampton NHS Foundation Trust
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1. Study Identification

Unique Protocol Identification Number
NCT00551122
Brief Title
Gemcitabine, Paclitaxel, Ifosfamide, and Cisplatin in Treating Patients With Progressive or Relapsed Metastatic Germ Cell Tumors
Acronym
GemTIP
Official Title
Phase I/II Multicentre Trial of Salvage Chemotherapy With Gem-TIP for Relapsed Germ Cell Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2007
Overall Recruitment Status
Unknown status
Study Start Date
November 2006 (undefined)
Primary Completion Date
April 2013 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southampton
Collaborators
University Hospital Southampton NHS Foundation Trust

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors, Extragonadal Germ Cell Tumor, Ovarian Cancer, Testicular Germ Cell Tumor
Keywords
recurrent malignant testicular germ cell tumor, testicular seminoma, recurrent ovarian germ cell tumor, stage IV ovarian germ cell tumor, stage III malignant testicular germ cell tumor, testicular choriocarcinoma and seminoma, testicular embryonal carcinoma and seminoma, testicular embryonal carcinoma and teratoma with seminoma, testicular embryonal carcinoma and yolk sac tumor with seminoma, testicular yolk sac tumor and teratoma with seminoma, recurrent extragonadal non-seminomatous germ cell tumor, recurrent extragonadal seminoma, stage IV extragonadal non-seminomatous germ cell tumor, stage IV extragonadal seminoma, recurrent extragonadal germ cell tumor, ovarian mixed germ cell tumor, adult central nervous system germ cell tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
23 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Paclitaxel, gemcitabine, cisplatin, ifosfamide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Biological
Intervention Name(s)
lenograstim
Intervention Type
Biological
Intervention Name(s)
pegfilgrastim
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
gemcitabine hydrochloride
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Primary Outcome Measure Information:
Title
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
Title
Response rates (phase I)
Time Frame
end of study
Title
Failure-free survival (phase I)
Time Frame
end of study
Title
Utility of positron emission tomography scanning after Gem-TIP chemotherapy (phase I)
Time Frame
end of study
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
G. Mead, MD
Organizational Affiliation
University Hospital Southampton NHS Foundation Trust
Official's Role
Study Chair
Facility Information:
Facility Name
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
City
Birmingham
State/Province
England
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael H. Cullen, MD
Phone
0121-627-2444
Facility Name
Southampton General Hospital
City
Southampton
State/Province
England
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
G. Mead, MD
Phone
44-23-8079-8639
Facility Name
Royal Marsden - Surrey
City
Sutton
State/Province
England
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert A. Huddart, MD
Phone
44-20-8661-3457
Email
robert.huddart@icr.ac.uk

12. IPD Sharing Statement

Learn more about this trial

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

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