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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00003926
• Other study ID #: 1997LS053
• Secondary ID: UMN-MT-9713UMN-9
• Status: Terminated
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: November 27, 2017
• Start date: November 1998
• Est. completion date: August 2003

Study information

• Verified date: November 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: August 2003
• Est. primary completion date: August 2002
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Carcinoma, Renal Cell
• Central Nervous System Neoplasms
• Childhood Germ Cell Tumor
• Chordoma
• Kidney Cancer
• Kidney Neoplasms
• Liver Cancer
• Liver Neoplasms
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Nervous System Neoplasms
• Neuroblastoma
• Ovarian Cancer
• Retinoblastoma
• Sarcoma

Intervention

Drug:
• 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.
• busulfan
Patients receive oral busulfan every 6 hours on days -8 to -6.
• filgrastim
All patients receive filgrastim (G-CSF) IV for 1 week.
• melphalan
melphalan intravenous (IV) over 30 minutes on days -5 and -4
• thiotepa
thiotepa intravenous (IV) over 2 hours on days -3 and -2.

Procedure:
• peripheral blood stem cell transplantation (PBSC)
PBSC are reinfused on day 0

Locations

Country	Name	City	State
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States,