Erlotinib and Temozolomide in Treating Young Patients With Recurrent or Refractory Solid Tumors

NCT ID: NCT00077454

Last Updated: 2013-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29

Brief Summary

This phase I trial is studying the side effects and best dose of erlotinib when given with temozolomide in treating young patients with recurrent or refractory solid tumors. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving erlotinib with temozolomide may kill more tumor cells.

Detailed Description

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.

Conditions

Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Brain Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (erlotinib hydrochloride, temozolomide)

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.

Group Type: EXPERIMENTAL

erlotinib hydrochloride

Intervention Type: DRUG

Given orally (PO)

temozolomide

Intervention Type: DRUG

Given PO

pharmacological study

Intervention Type: OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

erlotinib hydrochloride

Given orally (PO)

Intervention Type: DRUG

temozolomide

Given PO

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

CP-358,774; erlotinib; OSI-774; SCH 52365; Temodal; Temodar; TMZ; pharmacological studies

Eligibility 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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Regina Jakacki

Role: PRINCIPAL_INVESTIGATOR

COG Phase I Consortium

Locations

COG Phase I Consortium

Arcadia, California, United States

Countries

United States

Other Identifiers

ADVL0214

Identifier Type: -

Identifier Source: secondary_id

CDR0000350336

Identifier Type: -

Identifier Source: secondary_id

COG-ADVL0214

Identifier Type: -

Identifier Source: secondary_id

NCI-04-C-0256

Identifier Type: -

Identifier Source: secondary_id

U01CA097452

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01808

Identifier Type: -

Identifier Source: org_study_id

NCT00089934

Identifier Type: -

Identifier Source: nct_alias