Temozolomide, Vincristine, and Irinotecan in Treating Young Patients With Refractory Solid Tumors
Information source: Children's Oncology Group
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Brain and Central Nervous System Tumors; Unspecified Childhood Solid Tumor, Protocol Specific
Intervention: irinotecan hydrochloride (Drug); temozolomide (Drug); vincristine sulfate (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Children's Oncology Group Official(s) and/or principal investigator(s): Lars M. Wagner, MD, Study Chair, Affiliation: Children's Hospital Medical Center, Cincinnati John P. Perentesis, MD, Study Chair, Affiliation: Children's Hospital Medical Center, Cincinnati
Summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide, vincristine, and irinotecan,
work in different ways to stop the growth of tumor cells, either by killing the cells or by
stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill
more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when
given together with temozolomide and vincristine in treating young patients with refractory
solid tumors.
Clinical Details
Official title: A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Determine maximum tolerated dose (MTD) of oral irinotecan
Secondary outcome: To preliminarily define the antitumor activity
Detailed description:
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended phase II dose of irinotecan when
administered with temozolomide and vincristine in young patients with refractory solid
tumors, including brain tumors.
- Determine the toxic effects of this regimen in these patients.
- Compare the toxic effects of this regimen in patients with low- vs high-risk UGT1A1
genotypes.
- Determine the pharmacokinetics of irinotecan in these patients.
Secondary
- Determine, preliminarily, the antitumor activity of this regimen in these patients.
- Correlate UGT1A1, UGT1A7, UGT1A9, and BCRP genotypes with the pharmacokinetics and
pharmacodynamics of irinotecan and its metabolites in these patients.
OUTLINE: This is a multicenter, dose-escalation study of irinotecan. Patients are stratified
according to UGT1A1 genotype (high-risk [7/7 or 6/7 genotype AND bilirubin ≥ 0. 6 mg/dL] vs
low-risk [absence of high-risk criteria]) if a high-risk patient experiences a dose-limiting
toxicity (DLT).
Patients receive oral temozolomide on days 1-5 and oral irinotecan on days 1-5 and 8-12.
Patients also receive vincristine IV over 1 minute on days 1 and 8. Treatment repeats every
21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
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 6
patients experience DLT.
After completion of study treatment, patients are followed for 1 month and then annually
thereafter.
PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 18 months.
Eligibility
Minimum age: 1 Year.
Maximum age: 21 Years.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- Histologically confirmed* malignant solid tumor, including brain tumor, at original
diagnosis or relapse
- Refractory disease NOTE: *Histologic confirmation not required for intrinsic
brain stem tumors
- Measurable or evaluable disease
- No known curative therapy OR therapy proven to prolong survival with an acceptable
quality of life exists
- No known bone marrow metastases
PATIENT CHARACTERISTICS:
Age
- 1 to 21
Performance status
- Lansky 50-100% (for patients ≤ 10 years of age)
- Karnofsky 50-100% (for patients > 10 years of age)
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3 (transfusion independent)
- Hemoglobin ≥ 8. 0 g/dL (RBC transfusions allowed)
Hepatic
- ALT ≤ 110 U/L (upper limit of normal [ULN] for ALT is 45 U/L)
- Bilirubin ≤ 1. 5 times ULN
- Albumin ≥ 2 g/dL
Renal
- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
- Creatinine based on age as follows:
- No greater than 0. 8 mg/dL (for patients ≤ 5 years of age)
- No greater than 1. 0 mg/dL (for patients 6 to 10 years of age)
- No greater than 1. 2 mg/dL (for patients 11 to 15 years of age)
- No greater than 1. 5 mg/dL (for patients > 15 years of age)
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Neurologic deficits in patients with CNS tumors must be stable for ≥ 1 week prior to
study entry
- No uncontrolled infection
- No documented allergy to cephalosporins or dacarbazine
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Recovered from prior immunotherapy
- At least 3 months since prior stem cell transplantation or rescue without total-body
irradiation
- No evidence of active graft-versus-host disease
- At least 7 days since prior antineoplastic biologic agents
- At least 7 days since prior hematopoietic growth factors
- No concurrent biologic therapy or immunotherapy
- No concurrent prophylactic filgrastim (G-CSF) during the first course of study
treatment
Chemotherapy
- Recovered from prior chemotherapy
- Prior temozolomide, vincristine, irinotecan, or topotecan allowed
- No prior coadministration of temozolomide and irinotecan
- No disease progression during treatment with either irinotecan or temozolomide
- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for
nitrosoureas)
- No other concurrent chemotherapy
Endocrine therapy
- Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for
≥ 7 days prior to study entry
Radiotherapy
- Recovered from prior radiotherapy
- At least 6 months since prior total-body irradiation, craniospinal radiotherapy, or
radiotherapy to ≥ 50% of the pelvis
- At least 6 weeks since other prior substantial bone marrow radiotherapy
- At least 2 weeks since prior local palliative radiotherapy (small port)
- No concurrent radiotherapy
Surgery
- Not specified
Other
- No other concurrent investigational drugs
- No other concurrent anticancer therapy
- No concurrent enzyme-inducing anticonvulsants, including any of the following:
- Phenobarbital
- Phenytoin
- Carbamazepine
- Oxcarbazepine
- No concurrent administration of any of the following:
- Rifampin
- Voriconazole
- Itraconazole
- Ketoconazole
- Aprepitant
- Hypericum perforatum (St. John's wort)
- No concurrent treatment for clostridium difficile infection
Locations and Contacts
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham, Birmingham, Alabama 35294, United States
Children's Hospital of Orange County, Orange, California 92868, United States
Stanford Cancer Center, Stanford, California 94305-5824, United States
Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States
Masonic Cancer Center at University of Minnesota, Minneapolis, Minnesota 55455, United States
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center, New York, New York 10032, United States
SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, United States
Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada
Oregon Health and Science University Cancer Institute, Portland, Oregon 97239-3098, United States
Lehigh Valley Hospital - Muhlenberg, Bethlehem, Pennsylvania 18107, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-9786, United States
Hopital Sainte Justine, Montreal, Quebec H3T 1C5, Canada
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas, Texas 75390, United States
Children's Hospital and Regional Medical Center - Seattle, Seattle, Washington 98105, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: October 2005
Last updated: February 18, 2014
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