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

Sponsored by:	Southampton General Hospital
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00551122

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	Drug: cisplatin Drug: filgrastim Drug: gemcitabine hydrochloride Drug: ifosfamide Drug: lenograstim Drug: paclitaxel Drug: pegfilgrastim	Phase I Phase II

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Ifosfamide Filgrastim Cisplatin Gemcitabine hydrochloride Gemcitabine Paclitaxel Pegfilgrastim Lenograstim

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Phase I/II Multicentre Trial of Salvage Chemotherapy With Gem-TIP for Relapsed Germ Cell Cancer

Further study details as provided by National Cancer Institute (NCI):

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) [ Designated as safety issue: Yes ]
Response rates (phase I) [ Designated as safety issue: No ]
Failure-free survival (phase I) [ Designated as safety issue: No ]
Utility of positron emission tomography scanning after Gem-TIP chemotherapy (phase I) [ 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) [ Designated as safety issue: No ]

Estimated Enrollment:	23
Study Start Date:	November 2006

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

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

Locations

United Kingdom, England
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
Royal Marsden - Surrey	Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Robert A. Huddart, MD 44-20-8661-3457 robert.huddart@icr.ac.uk
Southampton General Hospital	Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: G. Mead, MD 44-23-8079-8639

Sponsors and Collaborators

Southampton General Hospital

Investigators

Study Chair:

G. Mead, MD

Southampton General Hospital

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000572096, USCTU-UR1002-GEM-TIP, EU-20769, EUDRACT-2004-004804-19
Study First Received:	October 25, 2007
Last Updated:	October 8, 2008
ClinicalTrials.gov Identifier:	NCT00551122
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Gonadal Disorders
Seminoma
Urogenital Neoplasms
Nonseminomatous germ cell tumor
Ovarian Diseases
Central Nervous System Neoplasms
Genital Diseases, Female
Cisplatin
Neoplasms, Germ Cell and Embryonal
Gemcitabine
Nervous System Neoplasms
Endocrine Gland Neoplasms
Extragonadal Germ Cell Tumor
Ovarian cancer
Ovarian Neoplasms

Lenograstim
Choriocarcinoma
Genital Neoplasms, Female
Endocrine System Diseases
Testicular Neoplasms
Malignant germ cell tumor
Recurrence
Carcinoma
Ifosfamide
Paclitaxel
Mechlorethamine
Testicular cancer
Endocrinopathy
Teratoma
Isophosphamide mustard

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms by Site
Therapeutic Uses
Alkylating Agents
Neoplasms by Histologic Type
Nervous System Diseases
Mitosis Modulators

Adjuvants, Immunologic
Enzyme Inhibitors
Antimitotic Agents
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Adnexal Diseases
Neoplasms
Radiation-Sensitizing Agents
Tubulin Modulators
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 15, 2009