Brain and Central Nervous System Tumors, Extragonadal Germ Cell Tumor, Ovarian Cancer, Teratoma, Testicular Germ Cell Tumor
Conditions
Keywords
recurrent ovarian germ cell tumor, stage III ovarian germ cell tumor, stage IV ovarian germ cell tumor, recurrent malignant testicular germ cell tumor, adult central nervous system germ cell tumor, stage III malignant testicular germ cell tumor, stage II malignant testicular germ cell tumor, recurrent extragonadal non-seminomatous germ cell tumor, recurrent extragonadal seminoma, stage III extragonadal non-seminomatous germ cell tumor, stage III extragonadal seminoma, stage IV extragonadal non-seminomatous germ cell tumor, stage IV extragonadal seminoma, recurrent extragonadal germ cell tumor, adult teratoma, testicular immature teratoma, testicular mature teratoma
Brief summary
RATIONALE: Drugs used in chemotherapy, such as paclitaxel, ifosfamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. An autologous peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more tumor cells are killed. PURPOSE: This phase I/II trial is studying the side effects and best dose of ifosfamide when given together with paclitaxel and carboplatin followed by an autologous stem cell transplant and to see how well they work in treating patients with germ cell tumors that did not respond to cisplatin.
Detailed description
OBJECTIVES: * Determine the safety of paclitaxel and ifosfamide followed by dose-escalated, dose-intensive paclitaxel, carboplatin, and ifosfamide with autologous peripheral blood stem cell support in patients with cisplatin-resistant germ cell tumor. (Phase I) * Determine the maximum tolerated dose of paclitaxel, carboplatin, and ifosfamide when given with a high-dose treatment program in these patients. (Phase I) * Determine the efficacy of this regimen when given as salvage therapy in the second-line or third-line setting, in terms of complete response, in these patients. (Phase II) OUTLINE: This is a phase I, dose-escalation study of paclitaxel, carboplatin, and ifosfamide followed by a phase II, open-label study. * Phase I: * Paclitaxel, ifosfamide, and autologous peripheral blood stem cell (PBSC) collection: Patients receive paclitaxel IV over 3 hours on day 1 and ifosfamide IV over 2 hours on days 1-3. Patients undergo leukapheresis on days 11-13. Patients also receive filgrastim (G-CSF) subcutaneously (SC) twice daily beginning on day 3 and continuing until leukapheresis is completed. Beginning on day 14 or 21, patients may receive a second course of paclitaxel, ifosfamide, and G-CSF. Patients may also undergo additional leukapheresis. * Paclitaxel, carboplatin, ifosfamide, and autologous PBSC transplantation: Patients receive paclitaxel IV over 3 hours, high-dose carboplatin IV over 30 minutes, and ifosfamide IV over 4 hours on days 1-3. Patients also receive G-CSF SC beginning on day 3 and continuing until blood counts recover. Patients undergo reinfusion of autologous PBSCs on day 5. Treatment repeats every 21-28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of paclitaxel, carboplatin, and ifosfamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. * Phase II: Patients receive treatment as in phase I with paclitaxel, carboplatin, and ifosfamide at the MTD determined in phase I. After completion of study treatment, patients are followed periodically for 1 year and then annually thereafter.
Interventions
BIOLOGICALfilgrastim
DRUGcarboplatin
DRUGifosfamide
DRUGpaclitaxel
PROCEDUREautologous hematopoietic stem cell transplantation
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
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed germ cell tumor (GCT) * Primary CNS GCT allowed * Unidimensionally measurable disease OR elevated serum tumor markers (alpha-fetoprotein and/or human chorionic gonadotropin) * Advanced disease * Disease resistant to a cisplatin-based chemotherapy regimen (i.e., failed to achieve a durable complete response to cisplatin) * Known residual disease after post-chemotherapy surgery allowed PATIENT CHARACTERISTICS: * Platelet count ≥ 100,000/mm\^3 * WBC ≥ 3,000/mm\^3 * Creatinine clearance \> 50 mL/min (unless due to tumor obstructing the ureters) * AST and ALT \< 2 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active infection * Negative serology for HIV type I and II, human T-lymphotropic virus type I and II, hepatitis B or C virus, syphilis, and cytomegalovirus * Hepatitis C negative serology by RIBA or PCR * Adequate medical condition for general anesthesia PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from recent surgery * At least 3 weeks since prior chemotherapy * No prior high-dose therapy with autologous bone marrow transplantation * No other concurrent chemotherapy * No other concurrent treatment (e.g., surgery or radiotherapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response | 2 year | Response assessed at the completion of therapy (after four to five cycles of chemotherapy and after surgery if necessary) Complete Response (CR): A complete response is defined as one of the following: * Complete disappearance of all clinical and radiographic and biochemical (normal AFP and HCG) evidence of disease for a minimum of 4 weeks (CR to chemotherapy). * Complete disappearance of all biochemical evidence of disease with resection of residual radiographic masses that prove to be negative for residual GCT; this includes both mature teratoma and necrotic debris (CR to chemotherapy) for a minimum of 4 weeks. * Complete disappearance of all biochemical evidence of disease with complete surgical excision of all residual radiographic masses that, if pathologically positive for residual malignant GCT, show margins to microscopically free of disease (CR to chemotherapy + surgery). Patients must be free of disease for a minimum of 4 weeks. |
| Maximum Tolerated Dose of Ifosfamide | 4 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy With Stem Cell Support This is a phase I/II trial of sequential accelerated chemotherapy cycles with paclitaxel/ifosfamide and paclitaxel/ifosfamide and carboplatin administered with G-CSF and PBSC support. During phase I, carboplatin, ifosfamide, and paclitaxel will be dose escalated to determine the MTD. Additional patients will be enrolled in the Phase II portion of the study following the determination of the MTD of Ifosfamide and paclitaxel, to bring the total possible number of patients treated at the MTD to 38.
filgrastim
carboplatin
ifosfamide
paclitaxel
autologous hematopoietic stem cell transplantation
peripheral blood stem cell transplantation | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Removed pior to the high-dose portion | 3 |
Baseline characteristics
| Characteristic | Chemotherapy With Stem Cell Support |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 9 / 26 |
Outcome results
Primary
Maximum Tolerated Dose of Ifosfamide
Time frame: 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chemotherapy With Stem Cell Support | Maximum Tolerated Dose of Ifosfamide | 9990 mg/m2 |
Primary
Response
Response assessed at the completion of therapy (after four to five cycles of chemotherapy and after surgery if necessary) Complete Response (CR): A complete response is defined as one of the following: * Complete disappearance of all clinical and radiographic and biochemical (normal AFP and HCG) evidence of disease for a minimum of 4 weeks (CR to chemotherapy). * Complete disappearance of all biochemical evidence of disease with resection of residual radiographic masses that prove to be negative for residual GCT; this includes both mature teratoma and necrotic debris (CR to chemotherapy) for a minimum of 4 weeks. * Complete disappearance of all biochemical evidence of disease with complete surgical excision of all residual radiographic masses that, if pathologically positive for residual malignant GCT, show margins to microscopically free of disease (CR to chemotherapy + surgery). Patients must be free of disease for a minimum of 4 weeks.
Time frame: 2 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemotherapy With Stem Cell Support | Response | Complete Response (CR) | 12 participants |
| Chemotherapy With Stem Cell Support | Response | Incomplete Response (IR) | 6 participants |
| Chemotherapy With Stem Cell Support | Response | Partial Response (PR) | 5 participants |