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

This study has been terminated.
(Withdrawn due to slow accrual)
Sponsor:
Information provided by:
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00003926
First received: November 1, 1999
Last updated: August 20, 2010
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Childhood Germ Cell Tumor
Chordoma
Kidney Cancer
Liver Cancer
Neuroblastoma
Ovarian Cancer
Retinoblastoma
Sarcoma
Drug: amifostine trihydrate
Drug: busulfan
Drug: filgrastim
Drug: melphalan
Drug: thiotepa
Procedure: peripheral blood stem cell transplantation (PBSC)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
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

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Enrollment: 13
Study Start Date: November 1998
Study Completion Date: August 2003
Primary Completion Date: August 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Solid/brain tumor patients (1-18 years)
Patients with solid tumor or brain tumor in the 1-18 years old stratum.
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.

Other Name: Ethyol
Drug: busulfan
Patients receive oral busulfan every 6 hours on days -8 to -6.
Other Name: Busulfex
Drug: filgrastim
All patients receive filgrastim (G-CSF) IV for 1 week.
Other Names:
  • granulocyte colony-stimulating factor
  • G-CSF
Drug: melphalan
melphalan intravenous (IV) over 30 minutes on days -5 and -4
Other Name: Alkeran
Drug: thiotepa
thiotepa intravenous (IV) over 2 hours on days -3 and -2.
Other Name: Thioplex
Procedure: peripheral blood stem cell transplantation (PBSC)
PBSC are reinfused on day 0
Other Name: bone marrow transplant
Experimental: Solid/brain tumor patients (19-45 years)
Patients with solid tumor or brain tumor in the 19-45 years old stratum.
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.

Other Name: Ethyol
Drug: busulfan
Patients receive oral busulfan every 6 hours on days -8 to -6.
Other Name: Busulfex
Drug: filgrastim
All patients receive filgrastim (G-CSF) IV for 1 week.
Other Names:
  • granulocyte colony-stimulating factor
  • G-CSF
Drug: melphalan
melphalan intravenous (IV) over 30 minutes on days -5 and -4
Other Name: Alkeran
Drug: thiotepa
thiotepa intravenous (IV) over 2 hours on days -3 and -2.
Other Name: Thioplex
Procedure: peripheral blood stem cell transplantation (PBSC)
PBSC are reinfused on day 0
Other Name: bone marrow transplant

Detailed 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.

  Eligibility

Ages Eligible for Study:   1 Year to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003926

Locations
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Study Chair: John P. Perentesis, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: John Perentesis, MD, Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00003926     History of Changes
Other Study ID Numbers: 1997LS053, UMN-MT-9713, UMN-9712M00074
Study First Received: November 1, 1999
Last Updated: August 20, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
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

Additional relevant MeSH terms:
Sarcoma
Carcinoma, Renal Cell
Kidney Neoplasms
Neuroblastoma
Neoplasms, Germ Cell and Embryonal
Liver Neoplasms
Ovarian Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Retinoblastoma
Neoplasms
Chordoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Nerve Tissue
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on September 22, 2014