Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Irinotecan and Cisplatin With or Without Amifostine in Treating Children With Solid Tumors That Have Not Responded to Previous Therapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Supportive care, Treatment	Closed	1 to 21	NCI	POG-9970 CCG-P9970, NCT00004919, P9970

Objectives

I. Determine the maximum tolerated dose (MTD) of irinotecan when administered 
with cisplatin, with or without amifostine, to children with refractory solid 
tumors.

II. Determine the dose limiting toxicities of the combination of irinotecan 
and cisplatin, with and without amifostine, in this patient population.

III. Determine the pharmacokinetics of cisplatin with and without amifostine 
in these patients.

IV. Quantify the leukocyte DNA-platinum adduct formation, with and without 
amifostine, and correlate it with response and toxicity in these patients.

V. Determine the safety and efficacy of the doses and schedules of 
administration to be used in phase II clinical trials.

Entry Criteria

Disease Characteristics:

Histologically confirmed solid tumor that is refractory to standard therapy or
for which no effective therapy exists
 Brainstem gliomas allowed without histologic diagnosis
 Brain tumors allowed provided not receiving anticonvulsants


Strata 2 and 3:
 No bone marrow involvement

Prior/Concurrent Therapy:

Biologic therapy:
 At least 1 week since prior biologic therapy and recovered
 At least 6 months since prior autologous or allogeneic bone marrow
  transplantation without total body irradiation (TBI)
 At least 1 week since prior growth factors
Strata 2 and 3:
 No prior stem cell transplantation (with or without TBI)  

Chemotherapy:
 At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for
  nitrosoureas) and recovered
 At least 1 week since prior antineoplastic agents
 No other concurrent chemotherapy
Strata 2 and 3:
 No more than 2 prior chemotherapy regimens (single or multiagent)

Endocrine therapy:
 If receiving dexamethasone for CNS tumors, must be on stable or decreasing
  dose for at least 2 weeks
 
Radiotherapy:
 At least 2 weeks since prior local radiation (small port)
 At least 6 months since prior craniospinal radiation 
 At least 6 months since prior radiation to at least 50% of pelvis
 At least 6 weeks since prior substantial bone marrow radiation
 Recovered from prior radiotherapy
Strata 2 and 3:
 No prior central axis radiotherapy 

Surgery:
 Not specified

Other:
 No other concurrent investigational agents
 No other concurrent anticancer therapy
 No concurrent anticonvulsants

Patient Characteristics:

Age:
 1 to 21

Performance status:
 Karnofsky 50-100% for patients over 10 years of age OR
 Lansky 50-100% for patients 10 years of age and under

Life expectancy:
 At least 8 weeks

Hematopoietic:
 Absolute neutrophil count at least 1,000/mm3
 Hemoglobin at least 8.0 g/dL
 Platelet count at least 100,000/mm3

Hepatic:
 Albumin at least 2.5 g/dL
 Bilirubin no greater than 1.5 mg/dL
 SGPT no greater than 2 times upper limit of normal

Renal:
 Creatinine normal for age OR
 GFR normal for age

Other:
 Not pregnant or nursing
 Negative pregnancy test
 Fertile patients must use effective contraception
 If CNS tumor, neurologic deficits relatively stable for at least 2 weeks
 Must be at least third percentile weight for height
 No concurrent significant systemic illness (e.g., infection, fever,
  mucositis, severe anorexia, and severe malnutrition)
 No uncontrolled infections
 No evidence of graft versus host disease

Expected Enrollment

A total of 3-30 patients will be accrued for this study within 2.5 years.

Outline

This is a dose escalation study of irinotecan.

Treatment A:  Patients receive cisplatin IV over 1 hour followed immediately 
by irinotecan IV over 90 minutes on days 1, 8, 15, and 22.  Courses repeat 
every 6 weeks.  Treatment continues for a minimum of 2 courses in the absence 
of unacceptable toxicity or disease progression.

Treatment B:  Patients receive therapy as in treatment A.  In addition, 
amifostine IV is administered over 15 minutes immediately before cisplatin.

Cohorts of 3-6 patients receive escalating doses of irinotecan until the 
maximum tolerated dose (MTD) is determined.  The MTD is defined as the dose 
preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting 
toxicities.  Once the MTD of treatment A is determined, additional patients 
are accrued to determine the MTD of treatment B.

If myelosuppression is the dose limiting toxicity of treatment A, then stratum 
1 closes and stratum 2 opens and these patients with less prior therapy 
receive treatment A.  Treatment B is then only open to stratum 3 patients.  

Patients are followed every 6 months for 4 years, then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Pediatric Oncology Group

Abdul Kader Souid, MD, PhD, Protocol chair		Ph: 315-464-5294; 877-464-8668

Registry Information
Official Title		A Trial of Irinotecan and Cisplatin in Children with Refractory Solid Tumors
Trial Start Date		1999-12-24
Registered in ClinicalTrials.gov		NCT00004919
Date Submitted to PDQ		2000-01-13
Information Last Verified		2002-04-01
NCI Grant/Contract Number		U01-CA57745

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