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Irinotecan and Cisplatin With or Without Amifostine in Treating Children With Solid Tumors That Have Not Responded to Previous Therapy
This study is ongoing, but not recruiting participants.
First Received: March 7, 2000   Last Updated: October 18, 2008   History of Changes
Sponsors and Collaborators: Pediatric Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004919
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs such as amifostine may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase I trial to study the effectiveness of irinotecan and cisplatin with or without amifostine in treating children who have solid tumors that have not responded to previous therapy.


Condition Intervention Phase
Cancer-Related Problem/Condition
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: amifostine trihydrate
Drug: cisplatin
Drug: irinotecan hydrochloride
Phase I

MedlinePlus related topics: Cancer
Drug Information available for: Cisplatin Amifostine Irinotecan U 101440E Irinotecan hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: A Trial of Irinotecan and Cisplatin in Children With Refractory Solid Tumors

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: December 1999
Detailed Description:

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.

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.

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

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004919

  Show 55 Study Locations
Sponsors and Collaborators
Pediatric Oncology Group
Investigators
Study Chair: Abdul Kader Souid, MD, PhD State University of New York - Upstate Medical University
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067601, POG-9970, CCG-P9970
Study First Received: March 7, 2000
Last Updated: October 18, 2008
ClinicalTrials.gov Identifier: NCT00004919     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
unspecified childhood solid tumor, protocol specific
drug/agent toxicity by tissue/organ

Study placed in the following topic categories:
Radiation-Protective Agents
Radiation-Sensitizing Agents
Amifostine
Cisplatin
Irinotecan
Antineoplastic Agents, Phytogenic
Camptothecin

Additional relevant MeSH terms:
Radiation-Protective Agents
Molecular Mechanisms of Pharmacological Action
Amifostine
Antineoplastic Agents
Irinotecan
Physiological Effects of Drugs
Enzyme Inhibitors
Protective Agents
Camptothecin
Pharmacologic Actions
Cisplatin
Radiation-Sensitizing Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 07, 2009