Paclitaxel, Ifosfamide, and Carboplatin Followed By Autologous Stem Cell Transplant in Treating Patients With Germ Cell Tumors That Did Not Respond to Cisplatin
Condition: Brain and Central Nervous System Tumors; Extragonadal Germ Cell Tumor; Ovarian Cancer; Teratoma; Testicular Germ Cell Tumor
MeSH terms: Neoplasms; Neoplasms, Germ Cell and Embryonal; Nervous System Neoplasms; Central Nervous System Neoplasms; Teratoma
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): filgrastim; carboplatin; ifosfamide; paclitaxel; autologous hematopoietic stem cell transplantation; peripheral blood stem cell transplantation
Intervention type(s): Biological; Drug; Drug; Drug; Procedure; Procedure
Intervention MeSH terms: Paclitaxel; Carboplatin; Ifosfamide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
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