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Temozolomide, Vincristine, and Irinotecan in Treating Young Patients With Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT00138216
Recruitment Status : Completed
First Posted : August 30, 2005
Last Update Posted : February 20, 2014
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE August 29, 2005
First Posted Date  ICMJE August 30, 2005
Last Update Posted Date February 20, 2014
Study Start Date  ICMJE October 2005
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2014)
Determine maximum tolerated dose (MTD) of oral irinotecan [ Time Frame: length of study ]
To estimate the maximum tolerated dose (MTD) of oral irinotecan administered on two different schedules together with fixed-dose temozolomide and vincristine in children with refractory solid tumors or brain tumors
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2014)
To preliminarily define the antitumor activity [ Time Frame: Length of study ]
To preliminarily define the antitumor activity of this drug combination within the confines of a Phase 1 study.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Temozolomide, Vincristine, and Irinotecan in Treating Young Patients With Refractory Solid Tumors
Official Title  ICMJE A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors
Brief 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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain and Central Nervous System Tumors
  • Unspecified Childhood Solid Tumor, Protocol Specific
Intervention  ICMJE
  • Drug: irinotecan hydrochloride
  • Drug: temozolomide
  • Drug: vincristine sulfate
Study Arms  ICMJE Experimental: Oral Irinotecan, temozolomide and vincristine sulfate
see detailed description
Interventions:
  • Drug: irinotecan hydrochloride
  • Drug: temozolomide
  • Drug: vincristine sulfate
Publications * Wagner LM, Perentesis JP, Reid JM, Ames MM, Safgren SL, Nelson MD Jr, Ingle AM, Blaney SM, Adamson PC. Phase I trial of two schedules of vincristine, oral irinotecan, and temozolomide (VOIT) for children with relapsed or refractory solid tumors: a Children's Oncology Group phase I consortium study. Pediatr Blood Cancer. 2010 Apr;54(4):538-45. doi: 10.1002/pbc.22407.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 18, 2014)
42
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE January 2011
Actual Primary Completion Date June 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00138216
Other Study ID Numbers  ICMJE ADVL0414
COG-ADVL0414 ( Other Identifier: Children's Oncology Group )
CDR0000440069 ( Other Identifier: ClinicalTrials.gov )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Lars M. Wagner, MD Children's Hospital Medical Center, Cincinnati
Study Chair: John P. Perentesis, MD Children's Hospital Medical Center, Cincinnati
PRS Account Children's Oncology Group
Verification Date February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP