Extragonadal Germ Cell Tumor, Ovarian Cancer, Testicular Germ Cell Tumor
Conditions
Keywords
recurrent malignant testicular germ cell tumor, recurrent ovarian germ cell tumor, extragonadal germ cell tumor
Brief summary
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, ifosfamide, carboplatin, and etoposide work in different ways to stop the growth of tumor cells, either by killing them or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell transplant may allow more chemotherapy to be given so that more tumor cells are killed. The design of this trial is a phase I/II trial of sequential accelerated chemotherapy cycles with taxol/ifosfamide and carboplatin/etoposide administered with G-CSF and PBSC support. PURPOSE: The purpose of this study is to determine the effects of an intensive sequence of chemotherapy drugs in patients with metastatic germ cell cancer. All of these chemotherapy drugs are known to be active in this disease.
Detailed description
OBJECTIVES: * Determine the safety of paclitaxel and ifosfamide followed by carboplatin and etoposide with stem cell support in patients with unfavorable germ cell tumors with unfavorable prognostic factors and resistance to cisplatin. * Determine the efficacy of this regimen as salvage therapy in these patients. * Escalate the dose of carboplatin based on a target area under the concentration time curve and renal function, and determine the pharmacokinetics of carboplatin in selected patients. * Determine the qualitative effects of paclitaxel and ifosfamide on hematopoietic progenitors in these patients. OUTLINE: This is a dose escalation study of carboplatin. * Part A: Patients receive paclitaxel IV continuously on day 1 and ifosfamide IV over 4 hours on days 2-4. Autologous peripheral blood stem cells (PBSC) are harvested on days 11-13. Filgrastim (G-CSF) is administered subcutaneously (SC) twice daily beginning 6 hours after completion of paclitaxel and ifosfamide infusions and continuing until the last day of leukapheresis. Treatment continues every 2 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Before beginning the first course of chemotherapy, autologous bone marrow (ABM) is harvested, if possible, in case insufficient peripheral blood stem cells (PBSC) are harvested. Patients who were unable to undergo harvest of ABM before the first course of chemotherapy undergo harvest of ABM before beginning the second course of chemotherapy. * Part B : Beginning 2 weeks after completion of regimen A, patients receive etoposide IV over 2 hours and carboplatin IV over 1 hour on days 1-3. PBSC are reinfused on day 5. G-CSF is administered SC twice daily beginning 6 hours after completion of etoposide and carboplatin infusions and continuing until blood counts recover. G-CSF is held on the morning of PBSC transplantation and restarted beginning 6 hours after completion of PBSC transplantation. Treatment continues every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with insufficient PBSC for the second course receive PBSC combined with ABM. Patients with insufficient PBSC for the third course receive ABM. During the second part, cohorts of 3-6 patients receive escalating doses of carboplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity. After completion of parts A and B, some patients may undergo resection of residual masses.
Interventions
BIOLOGICALfilgrastim
DRUGcarboplatin
DRUGetoposide
DRUGifosfamide
DRUGpaclitaxel
PROCEDUREperipheral blood stem cell transplantation
Sponsors
National Cancer Institute (NCI)
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male/Female with histologically confirmed GCT with review by the Department of Pathology at this center. * Patients with advanced GCT, including patients with: measurable or evaluable disease, * patients with only elevated serum tumor markers (AFP and/or HCG), or * patients with known residual disease after postchemotherapy surgery. Eligible patients must have established clinical resistance to cisplatin by their failure to achieve a durable CR to a cisplatin-based regimen. * Prior treatment limited to ≤ 6 prior cycles (≤ four cycles preferred) of cisplatin. (GROUP A) * Prior therapy \> 6 cycles of cisplatin. (GROUP B) * Therapy must have been discontinued at least 3 weeks before entry onto protocol. * Patients must have one or more unfavorable prognostic factors for achieving a CR to cisplatin-based salvage therapy. These are: * Extragonadal primary site. * Testis/ovarian primary site with the best response of an IR to first-line therapy, or a partial response with normal tumor markers of six months or less in duration. * Prior treatment with ifosfamide-containing therapy * General medical condition sufficient to allow for general anesthesia at the time of pheresis catheter placement. * Patients must have negative serology for Human Immunodeficiency Virus. * Laboratory criteria for protocol entry: WBC ≥ 3000/ul Platelets 3 100,000/ul Cr Clearance \> 50 cc/min\* \* (unless renal dysfunction is due to tumor obstructing the ureters in which case eligibility will be determined by the Principal Investigator). * Age ≥ 15 years. * Signed informed consent.
Exclusion criteria
* Presence of active infection * Concurrent treatment with chemotherapy or * Inability to comply with the treatment protocol or to undergo the specified follow-up tests for safety or effectiveness. * Prior high-dose therapy with AuBMT. * Patients must have recovered from recent surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Objective Response | 2 years | Overall Objective Response will be assessed prior to dose-intensive therapy and at the completion of therapy. Complete disappearance of all clinical, radiographic and biochemical (normal AFP and HCG) evidence of disease for a minimum of 4 weeks (CR to chemotherapy). Patients must be free of disease for a minimum of 4 weeks. Partial Response: Complete disappearance of all biochemical evidence of disease in patients without a surgical procedure for a residual radiographic mass. Patients must demonstrate no biochemical recurrence or progression of radiographic masses for a minimum of four weeks (PR to chemotherapy} |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Group A: Prior Treatment Limited to \<= 6 Cycles of Cisplatin | 92 |
| Group B Group B: Prior Treatment Limited to \> 6 Cycles of Cisplatin | 16 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 0 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 89 Participants | 16 Participants | 105 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 90 Participants | 15 Participants | 105 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 92 / 92 | 15 / 16 |
| serious Total, serious adverse events | 7 / 92 | 2 / 16 |
Outcome results
Primary
Overall Objective Response
Overall Objective Response will be assessed prior to dose-intensive therapy and at the completion of therapy. Complete disappearance of all clinical, radiographic and biochemical (normal AFP and HCG) evidence of disease for a minimum of 4 weeks (CR to chemotherapy). Patients must be free of disease for a minimum of 4 weeks. Partial Response: Complete disappearance of all biochemical evidence of disease in patients without a surgical procedure for a residual radiographic mass. Patients must demonstrate no biochemical recurrence or progression of radiographic masses for a minimum of four weeks (PR to chemotherapy}
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A | Overall Objective Response | Complete Response (CR) | 50 participants |
| Group A | Overall Objective Response | Incomplete Response (IR) | 36 participants |
| Group A | Overall Objective Response | Partial Response (PR) | 5 participants |
| Group B | Overall Objective Response | Complete Response (CR) | 4 participants |
| Group B | Overall Objective Response | Incomplete Response (IR) | 8 participants |
| Group B | Overall Objective Response | Partial Response (PR) | 3 participants |