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

University of Minnesota (UMN)

Status and phase: Terminated; Phase 1

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

Treatments: Drug: melphalan; Procedure: peripheral blood stem cell transplantation (PBSC); Drug: busulfan; Drug: amifostine trihydrate; Drug: thiotepa; Drug: filgrastim

Study type: Interventional

Funder types: Other

Identifiers

NCT00003926

UMN-9712M00074 (Other Identifier)

1997LS053

UMN-MT-9713 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 13 patients

Sex: All

Ages: 1 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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13 participants in 2 patient groups

Solid/brain tumor patients (1-18 years)

Experimental group

Description:

Patients with solid tumor or brain tumor in the 1-18 years old stratum.

Treatment:

Drug: filgrastim

Drug: thiotepa

Procedure: peripheral blood stem cell transplantation (PBSC)

Drug: busulfan

Drug: amifostine trihydrate

Drug: melphalan

Solid/brain tumor patients (19-45 years)

Experimental group

Description:

Patients with solid tumor or brain tumor in the 19-45 years old stratum.

Treatment:

Drug: filgrastim

Drug: thiotepa

Procedure: peripheral blood stem cell transplantation (PBSC)

Drug: busulfan

Drug: amifostine trihydrate

Drug: melphalan