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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00077454
Recruitment Status : Completed
First Posted : February 12, 2004
Last Update Posted : June 5, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
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 Drug: erlotinib hydrochloride Drug: temozolomide Other: pharmacological study Other: laboratory biomarker analysis Phase 1

Detailed Description:


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.


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 95 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : February 2004
Actual Primary Completion Date : September 2007

Arm Intervention/treatment
Experimental: 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.
Drug: erlotinib hydrochloride
Given orally (PO)
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774

Drug: temozolomide
Given PO
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: 56 days (2 courses) ]
  2. Maximum-tolerated dose (MTD) based on the incidence of DLT as assessed by NCI CTCAE version 3.0 [ Time Frame: 56 days (2 courses) ]
  3. Pharmacokinetics of erlotinib hydrochloride [ Time Frame: At baseline and at 0.5, 1, 2, 4, 6, 8, and 24 hours of course 1 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00077454

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United States, California
COG Phase I Consortium
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Regina Jakacki COG Phase I Consortium

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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00077454     History of Changes
Obsolete Identifiers: NCT00089934
Other Study ID Numbers: NCI-2012-01808
U01CA097452 ( U.S. NIH Grant/Contract )
First Posted: February 12, 2004    Key Record Dates
Last Update Posted: June 5, 2013
Last Verified: June 2013

Additional relevant MeSH terms:
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Brain Neoplasms
Neoplasms, Germ Cell and Embryonal
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Rhabdomyosarcoma, Embryonal
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Neuroepithelial
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Muscle Tissue