Clinical trial NCT00003926: Amifostine to Protect From Side Effects of PSCT in Treating Patients With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Childhood Germ Cell Tumor
Chordoma
Kidney Cancer
Liver Cancer
Neuroblastoma
Ovarian Cancer
Retinoblastoma
Sarcoma
Keywords: 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
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2003-05-02
Enrollment: 13
Sex: ALL
Minimum age (years): 1
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: John P. Perentesis, MD
role: STUDY_CHAIR
References: