A Phase I Study of Single Agent OSI-774 (Tarceva) (NSC# 718781, IND# 63383) Followed by OSI-774 With Temozolomide for Patients With Selected Recurrent/Refractory Solid Tumors, Including Brain Tumors
erlotinib hydrochloride
+ temozolomide
+ pharmacological study
Astrocytoma+30
+ Brain Diseases
+ Brain Neoplasms
Treatment Study
Summary
Study start date: February 1, 2004
Actual date on which the first participant was enrolled.PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of erlotinib in children with recurrent or refractory solid tumors. II. Determine the dose-limiting toxic effects of this drug alone and with temozolomide in these patients. III. Determine the tolerability of this regimen in these patients. IV. Determine the pharmacokinetics of this regimen in these patients. SECONDARY OBJECTIVES: I. Determine, preliminarily, the antitumor activity of this regimen in these patients. OUTLINE: This is a 2-part, multicenter, dose-escalation study of erlotinib. Patients are stratified according to pretreatment (heavily pretreated \[received more than 2 prior multiagent myelosuppressive chemotherapy regimens OR received prior craniospinal or pelvic radiotherapy or bone marrow transplantation OR has bone marrow involvement\] vs less heavily pretreated).Part 1: Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 23 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib during course 1 only 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 toxicity. Part 2: Patients receive erlotinib (at the MTD) and temozolomide as in part 1. PROJECTED ACCRUAL: A total of 9-45 patients (9-24 for part 1 and up to 21 for part 2) will be accrued for this study.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.95 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Until 21 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria: * One of the following histologically confirmed solid tumors: * Brain tumors * Osteogenic sarcoma * Rhabdomyosarcoma * Soft tissue sarcoma (excluding Ewing's sarcoma) * Neuroblastoma * Germ cell tumors * Recurrent or refractory disease * No known curative therapy exists * Performance status - Karnofsky 50-100% (for patients age 11 to 21) * Performance status - Lansky 50-100% (for patients age 10 and under) * At least 8 weeks * Absolute neutrophil count \> 1,000/mm\^3 * Platelet count \> 100,000/mm\^3 (transfusion independent\*) * Hemoglobin \> 8.0 g/dL (transfusion allowed) * Bilirubin \< 1.5 times upper limit of normal (ULN) * ALT \< 2.5 times ULN * Albumin ≥ 2 g/dL * Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min * Creatinine based on age as follows: * ≤ 0.8 mg/dL for patients age 5 and under * ≤ 1.0 mg/dL for patients 6 to 10 * ≤ 1.2 mg/dL for patients 11 to 15 * ≤ 1.5 mg/dL for patients age 15 to 21 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to swallow tablets (for patients in part 2 only) * No uncontrolled infection * Recovered from all prior immunotherapy * At least 7 days since prior biologic therapy * At least 3 months since prior stem cell transplantation and no evidence of active graft-versus-host disease * More than 1 week since prior growth factors * No concurrent prophylactic growth factor therapy * No concurrent immunotherapy * No concurrent biologic therapy * More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered * No other concurrent chemotherapy * No concurrent systemic corticosteroids except for treatment of increased intracranial pressure or symptomatic tumor edema in patients with CNS tumors * No concurrent steroids as an antiemetic * Concurrent dexamethasone for patients with CNS tumors allowed provided patient has been on a stable or decreasing dose for at least 1 week before study entry * Recovered from all prior radiotherapy * At least 2 weeks since prior local palliative radiotherapy (small port) * At least 6 weeks since prior substantial bone marrow irradiation * At least 6 months since prior craniospinal radiotherapy * At least 6 months since prior radiotherapy to 50% or more of the pelvis * At least 8 weeks since prior standard-fraction radiotherapy for patients with recurrent brain tumors unless there is biopsy proof of recurrent tumor * Prior radiosurgery within the past 9 months allowed provided there is documentation of progressive disease by biopsy, positron-emission tomography (PET) scan, or MR spectroscopy * No concurrent radiotherapy * More than 1 week since prior CYP3A4 inhibitors * More than 4 weeks since prior CYP3A4 inducers * More than 5 days since prior proton-pump inhibitors * More than 2 days since prior H_2 blockers * No prior erlotinib * No concurrent enzyme-inducing anticonvulsants * No concurrent proton-pump inhibitors * No concurrent H2 blockers * No other concurrent investigational agents * Concurrent antacids allowed provided the antacid is not administered 2 hours before, during, and 2 hours after erlotinib administration
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location