Brain and Central Nervous System TumorsPhase 1NCT00138216
Temozolomide, Vincristine, and Irinotecan in Treating Young Patients With Refractory Solid Tumors
A Phase 1 study testing irinotecan hydrochloride, temozolomide and vincristine sulfate in people with Brain and Central Nervous System Tumors and Unspecified Childhood Solid Tumor, Protocol Specific, run by Children's Oncology Group at 18 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Brain and Central Nervous System Tumors, Unspecified Childhood Solid Tumor, Protocol Specific
- What is being tested?
- irinotecan hydrochloride, temozolomide and vincristine sulfate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 18 sitesin 2 countries
- Study dates
- Oct 2005to Jan 2011
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Trial locations and contacts
18 sites in 2 countries.
18 sites in 2 countries
United States16 sites
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18107
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, 35294
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Children's Memorial Hospital - Chicago
Chicago, Illinois, 60614
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, 75390
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202-5289
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, 10032
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-9786
Oregon Health and Science University Cancer Institute
Portland, Oregon, 97239-3098
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
Stanford Cancer Center
Stanford, California, 94305-5824
SUNY Upstate Medical University Hospital
Syracuse, New York, 13210
Canada2 sites
Hopital Sainte Justine
Montreal, Quebec, H3T 1C5
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
Official title: A Phase I Study of Temozolomide, Oral Irinotecan, and Vincristine for Children With Refractory Solid Tumors
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.
Read the 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.
- Conditions
- Brain and Central Nervous System Tumors, Unspecified Childhood Solid Tumor, Protocol Specific
- Being tested
- irinotecan hydrochloride, temozolomide, vincristine sulfate
- Keywords
- unspecified childhood solid tumor, protocol specific, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood brain stem glioma, recurrent childhood brain tumor, recurrent childhood ependymoma, recurrent childhood medulloblastoma, recurrent childhood supratentorial primitive neuroectodermal tumor, recurrent childhood visual pathway and hypothalamic glioma, childhood oligodendroglioma, childhood craniopharyngioma, childhood choroid plexus tumor, childhood infratentorial ependymoma, childhood supratentorial ependymoma, childhood high-grade cerebral astrocytoma, childhood low-grade cerebral astrocytoma, childhood central nervous system germ cell tumor, childhood grade I meningioma, childhood grade II meningioma, childhood grade III meningioma
- Medical subject headings
- Central Nervous System Neoplasms, Astrocytoma, Familial ependymoma, Medulloblastoma, Optic Nerve Glioma, Oligodendroglioma, Choroid Plexus Neoplasms, Rhabdoid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Oral Irinotecan, temozolomide and vincristine sulfate | Experimental | see detailed description Receives: Drug: irinotecan hydrochloride; Drug: temozolomide; Drug: vincristine sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine maximum tolerated dose (MTD) of oral irinotecan
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
Measured: length of study
Secondary outcomes (1)
To preliminarily define the antitumor activity
To preliminarily define the antitumor activity of this drug combination within the confines of a Phase 1 study.
Measured: Length of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2005 (estimated)
- Study startOct 2005
- Primary completionJun 2009
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Lars M. Wagner, MD, Study chair, Children's Hospital Medical Center, CincinnatiJohn P. Perentesis, MD, Study chair, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00138216
- Sponsor's protocol ID
- ADVL0414
- Other IDs
- COG-ADVL0414, CDR0000440069
- Status last verified
- Feb 2014
- First submitted
- 29 Aug 2005
- Last updated
- 2 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 20049936