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Sponsors and Collaborators: |
Pediatric Oncology Group National Cancer Institute (NCI) |
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Information provided by: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00004919 |
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 |
---|---|---|
Drug/Agent Toxicity by Tissue/Organ Unspecified Childhood Solid Tumor, Protocol Specific |
Drug: amifostine trihydrate Drug: cisplatin Drug: irinotecan hydrochloride |
Phase I |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | A Trial of Irinotecan and Cisplatin in Children With Refractory Solid Tumors |
Study Start Date: | December 1999 |
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.
Ages Eligible for Study: | 1 Year to 21 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
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
Study Chair: | Abdul Kader Souid, MD, PhD | State University of New York - Upstate Medical University |
Study ID Numbers: | CDR0000067601, POG-9970, CCG-P9970 |
Study First Received: | March 7, 2000 |
Last Updated: | May 9, 2009 |
ClinicalTrials.gov Identifier: | NCT00004919 History of Changes |
Health Authority: | United States: Federal Government |
unspecified childhood solid tumor, protocol specific drug/agent toxicity by tissue/organ |
Radiation-Protective Agents Radiation-Sensitizing Agents Amifostine Cisplatin |
Irinotecan Antineoplastic Agents, Phytogenic Camptothecin |
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 |