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

Condition(s) targeted: Drug Toxicity; Unspecified Childhood Solid Tumor, Protocol Specific

Intervention: amifostine trihydrate (Drug); cisplatin (Drug); irinotecan hydrochloride (Drug); chemoprotection (Procedure); chemotherapy (Procedure); supportive care/therapy (Procedure)

Phase: Phase 1

Status: No longer recruiting

Sponsored by: Pediatric Oncology Group

Official(s) and/or principal investigator(s):
Abdul Kader Souid, MD, PhD, Study Chair, Affiliation: SUNY Upstate Medical University Hospital

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.

Official title: A Trial of Irinotecan and Cisplatin in Children With Refractory Solid Tumors

Study design: Interventional, Treatment

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.

Minimum age: 1 Year. Maximum age: 21 Years. Gender(s): Both.

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

University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States

Children's Hospital Los Angeles, Los Angeles, California 90027-0700, United States

Children's Hospital of Orange County, Orange, California 92868, United States

City of Hope National Medical Center, Duarte, California 91010, United States

Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095-1781, United States

Stanford University Medical Center, Stanford, California 94305-5408, United States

UCSF Cancer Center and Cancer Research Institute, San Francisco, California 94143-0128, United States

University of California San Diego Cancer Center, La Jolla, California 92093-0658, United States

Children's National Medical Center, Washington, District of Columbia 20010-2970, United States

University of Florida Health Science Center, Gainesville, Florida 32610-0296, United States

Emory University Hospital - Atlanta, Atlanta, Georgia 30322, United States

Children's Memorial Hospital, Chicago, Chicago, Illinois 60614, United States

Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois 60611-3013, United States

Indiana University Cancer Center, Indianapolis, Indiana 46202-5289, United States

University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States

Boston Floating Hospital Infants and Children, Boston, Massachusetts 02111, United States

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States

Children's Hospital of Michigan, Detroit, Michigan 48201, United States

University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0752, United States

Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States

University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, United States

University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States

Cardinal Glennon Children's Hospital, Saint Louis, Missouri 63104, United States

Children's Mercy Hospital, Kansas City, Missouri 64108, United States

Washington University School of Medicine, Saint Louis, Missouri 63110, United States

Cancer Institute of New Jersey, New Brunswick, New Jersey 08901, United States

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

Columbia Presbyterian Hospital, New York, New York 10032, United States

Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States

NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York, New York 10016, United States

Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States

State University of New York - Upstate Medical University, Syracuse, New York 13210, United States

Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States

Children's Hospital Medical Center - Cincinnati, Cincinnati, Ohio 45229-3039, United States

Children's Hospital of Columbus, Columbus, Ohio 43205-2696, United States

University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, United States

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States

Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada

McGill University Health Center - Montreal Children's Hospital, Montreal, Quebec H3H 1P3, Canada

Medical University of South Carolina, Charleston, South Carolina 29425-0721, United States

Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232-6838, United States

Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104, United States

Simmons Cancer Center - Dallas, Dallas, Texas 75235-9154, United States

Texas Children's Cancer Center, Houston, Texas 77030-2399, United States

University of Texas - MD Anderson Cancer Center, Houston, Texas 77030-4009, United States

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7811, United States

Primary Children's Medical Center, Salt Lake City, Utah 84113, United States

Royal Children's Hospital, Parkville, Victoria 3052, Australia

Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States

Princess Margaret Hospital for Children, Perth, Western Australia 6001, Australia

Midwest Children's Cancer Center, Milwaukee, Wisconsin 53226, United States

University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53792-6164, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: December 1999
Last updated: February 20, 2007