Clinical trial NCT00551122: Gemcitabine, Paclitaxel, Ifosfamide, and Cisplatin in Treating Patients With Progressive or Relapsed Metastatic Germ Cell Tumors
Official title: Phase I/II Multicentre Trial of Salvage Chemotherapy With Gem-TIP for Relapsed Germ Cell Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: University of Southampton
Sponsor class: OTHER
Collaborators: name: University Hospital Southampton NHS Foundation Trust
First posted: 2007-10-30
Enrollment: 23
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum tolerated dose of gemcitabine hydrochloride when administered with TIP chemotherapy comprising paclitaxel, ifosfamide, and cisplatin with growth factor support (phase I)
timeFrame: end of study
measure: Response rates (phase I)
timeFrame: end of study
measure: Failure-free survival (phase I)
timeFrame: end of study
measure: Utility of positron emission tomography scanning after Gem-TIP chemotherapy (phase I)
timeFrame: end of study
measure: Degree of dose intensification achieved with Gem-TIP chemotherapy relative to a previous Medical Research Council study with TIP alone (phase II)
timeFrame: end of study
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: G. Mead, MD
role: STUDY_CHAIR
References: