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

NCT ID: NCT00003926

Last Updated: 2017-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-11-30

Study Completion Date

2003-08-31

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.

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

Keywords

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Solid/brain tumor patients (1-18 years)

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

Group Type EXPERIMENTAL

amifostine trihydrate

Intervention Type DRUG

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.

busulfan

Intervention Type DRUG

Patients receive oral busulfan every 6 hours on days -8 to -6.

filgrastim

Intervention Type DRUG

All patients receive filgrastim (G-CSF) IV for 1 week.

melphalan

Intervention Type DRUG

melphalan intravenous (IV) over 30 minutes on days -5 and -4

thiotepa

Intervention Type DRUG

thiotepa intravenous (IV) over 2 hours on days -3 and -2.

peripheral blood stem cell transplantation (PBSC)

Intervention Type PROCEDURE

PBSC are reinfused on day 0

Solid/brain tumor patients (19-45 years)

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

Group Type EXPERIMENTAL

amifostine trihydrate

Intervention Type DRUG

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.

busulfan

Intervention Type DRUG

Patients receive oral busulfan every 6 hours on days -8 to -6.

filgrastim

Intervention Type DRUG

All patients receive filgrastim (G-CSF) IV for 1 week.

melphalan

Intervention Type DRUG

melphalan intravenous (IV) over 30 minutes on days -5 and -4

thiotepa

Intervention Type DRUG

thiotepa intravenous (IV) over 2 hours on days -3 and -2.

peripheral blood stem cell transplantation (PBSC)

Intervention Type PROCEDURE

PBSC are reinfused on day 0

Interventions

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amifostine trihydrate

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.

Intervention Type DRUG

busulfan

Patients receive oral busulfan every 6 hours on days -8 to -6.

Intervention Type DRUG

filgrastim

All patients receive filgrastim (G-CSF) IV for 1 week.

Intervention Type DRUG

melphalan

melphalan intravenous (IV) over 30 minutes on days -5 and -4

Intervention Type DRUG

thiotepa

thiotepa intravenous (IV) over 2 hours on days -3 and -2.

Intervention Type DRUG

peripheral blood stem cell transplantation (PBSC)

PBSC are reinfused on day 0

Intervention Type PROCEDURE

Other Intervention Names

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Ethyol Busulfex granulocyte colony-stimulating factor G-CSF Alkeran Thioplex bone marrow transplant

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
Minimum Eligible Age

1 Year

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Masonic Cancer Center, University of Minnesota

Principal Investigators

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John P. Perentesis, MD

Role: STUDY_CHAIR

Masonic Cancer Center, University of Minnesota

Locations

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University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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UMN-MT-9713

Identifier Type: OTHER

Identifier Source: secondary_id

UMN-9712M00074

Identifier Type: OTHER

Identifier Source: secondary_id

1997LS053

Identifier Type: -

Identifier Source: org_study_id