Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of high-dose chemotherapy. PURPOSE: Phase I trial to study the effectiveness of amifostine in protecting from the side effects of peripheral stem cell transplantation in treating patients who have high-risk or relapsed solid tumors.

Detailed Description
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OBJECTIVES: Determine the dose-limiting toxicity of amifostine chemoprotection with peripheral blood stem cell transplantation plus chemotherapy in patients with high-risk or relapsed solid tumors or brain tumors. Determine response or time to disease progression in patients treated with this regimen. OUTLINE: This is a dose-escalation study of amifostine. Patients are stratified according to age (1 to 18 vs 19 to 45 years). All patients receive filgrastim (G-CSF) IV for 1 week. On day 6 of G-CSF administration, patients undergo peripheral blood stem cell (PBSC) harvest followed by chemotherapy. Patients receive oral busulfan every 6 hours on days -8 to -6 followed by melphalan IV over 30 minutes on days -5 and -4 and thiotepa IV over 2 hours on days -3 and -2. Patients receive amifostine IV over 5 minutes beginning 30 minutes prior to melphalan and thiotepa administration on days -5 to -1. PBSC are reinfused on day 0. Cohorts of 3-6 patients receive escalating doses of amifostine until the maximum tolerated dose 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. Patients are followed on day 50; at 3, 6, and 9 months; and at 1, 2, and 3 years post PBSC transplantation. PROJECTED ACCRUAL: A maximum of 60 patients (30 per stratum) will be accrued for this study within 3 years.

Official Title
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A Phase I Study of the Chemoprotectant Amifostine With Autologous Stem Cell Transplantation for High Risk or Relapsed Pediatric Solid Tumors and Brain Tumors

Conditions
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Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Chordoma, Kidney Cancer, Liver Cancer, Neuroblastoma, Ovarian Cancer, Retinoblastoma, Sarcoma

Intervention / Treatment
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* Drug: amifostine trihydrate
* Drug: busulfan
* Drug: filgrastim
* Drug: melphalan
* Drug: thiotepa
* Procedure: peripheral blood stem cell transplantation (PBSC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed high-risk or relapsed solid tumors or brain tumors, including: Metastatic or relapsed Ewing's sarcoma Metastatic or relapsed rhabdomyosarcoma Refractory Wilms' tumor Diffuse anaplastic Wilms' tumor Stage III or IV neuroblastoma Recurrent retinoblastoma Metastatic or relapsed germ cell tumors Metastatic or relapsed other soft tissue sarcomas Small cell ovarian sarcoma Metastatic or relapsed primitive neuroectodermal tumors of the bone Recurrent brain tumors Desmoplastic small round cell tumors Recurrent or metastatic chordomas Metastatic or relapsed hepatoblastoma Patients receive peripheral blood stem cell transplantation only if in complete remission or in very good partial remission with no disease progression Must have radiologic, nuclear image, or histologic verification of relapse Age 1 to 45 Performance status:Karnofsky 70-100% Absolute neutrophil count greater than 1,000/mm^3 Platelet count greater than 100,000/mm^3 Hemoglobin count at least 10 g/dL Bilirubin less than 2 times upper limit of normal (ULN) SGOT or SGPT less than 2.5 times ULN Creatinine less than 2 times ULN Creatinine clearance greater than 70 mL/min Cardiac shortening fraction greater than 30% Cardiac ejection fraction greater than 45% At least 1 week since prior hematopoietic growth factor and recovered At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered Recovered from any prior therapy Exclusion Criteria: Osteogenic sarcoma Less than 4 months Uncontrolled bleeding Congestive heart failure Uncontrolled hypertension Asthma Pregnant or nursing Uncontrolled metabolic disease Active severe infection Allergy to aminothiol compounds Prior bone marrow transplantation Other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Solid/brain tumor patients (1-18 years)<br>Patients with solid tumor or brain tumor in the 1-18 years old stratum. | Drug: amifostine trihydrate<br>* Patients receive amifostine intravenous (IV) over 5 minutes beginning 30 minutes prior to melphalan and thiotepa administration on days -5 to -1. Cohorts of 3-6 patients receive escalating doses of amifostine until the maximum tolerated dose is determined.<br>* Other names: Ethyol;Drug: busulfan<br>* Patients receive oral busulfan every 6 hours on days -8 to -6.<br>* Other names: Busulfex;Drug: filgrastim<br>* All patients receive filgrastim (G-CSF) IV for 1 week.<br>* Other names: G-CSF;Drug: melphalan<br>* melphalan intravenous (IV) over 30 minutes on days -5 and -4<br>* Other names: Alkeran;Drug: thiotepa<br>* thiotepa intravenous (IV) over 2 hours on days -3 and -2.<br>* Other names: Thioplex;Procedure: peripheral blood stem cell transplantation (PBSC)<br>* PBSC are reinfused on day 0<br>* Other names: bone marrow transplant;|
| Experimental: Solid/brain tumor patients (19-45 years)<br>Patients with solid tumor or brain tumor in the 19-45 years old stratum. | Drug: amifostine trihydrate<br>* Patients receive amifostine intravenous (IV) over 5 minutes beginning 30 minutes prior to melphalan and thiotepa administration on days -5 to -1. Cohorts of 3-6 patients receive escalating doses of amifostine until the maximum tolerated dose is determined.<br>* Other names: Ethyol;Drug: busulfan<br>* Patients receive oral busulfan every 6 hours on days -8 to -6.<br>* Other names: Busulfex;Drug: filgrastim<br>* All patients receive filgrastim (G-CSF) IV for 1 week.<br>* Other names: G-CSF;Drug: melphalan<br>* melphalan intravenous (IV) over 30 minutes on days -5 and -4<br>* Other names: Alkeran;Drug: thiotepa<br>* thiotepa intravenous (IV) over 2 hours on days -3 and -2.<br>* Other names: Thioplex;Procedure: peripheral blood stem cell transplantation (PBSC)<br>* PBSC are reinfused on day 0<br>* Other names: bone marrow transplant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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soft tissue sarcoma, regional neuroblastoma, disseminated neuroblastoma, recurrent Wilms tumor, recurrent retinoblastoma, recurrent adult brain tumor, adult rhabdomyosarcoma, ovarian germ cell tumor, chordoma, ovarian sarcoma, unresectable neuroblastoma, desmoplastic small round cell tumor, rhabdomyosarcoma, Ewing sarcoma, neuroectodermal tumor, teratoma, malignant testicular germ cell tumor, malignant ovarian germ cell tumor, extragonadal germ cell tumor, malignant germ cell tumor, hepatoblastoma, liver cancer, medulloblastoma, cerebellar astrocytoma, brain stem glioma, glioma, cerebral astrocytoma, ependymoma