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

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Recurrent Childhood Medulloblastoma

Recurrent Neuroblastoma

Recurrent Osteosarcoma

Recurrent Childhood Soft Tissue Sarcoma

Recurrent Childhood Ependymoma

Recurrent Childhood Cerebellar Astrocytoma

Recurrent Childhood Cerebral Astrocytoma

Recurrent Childhood Malignant Germ Cell Tumor

Recurrent Childhood Brain Tumor

Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

Previously Treated Childhood Rhabdomyosarcoma

Recurrent Childhood Rhabdomyosarcoma

Treatments

Drug: temozolomide

Other: pharmacological study

Drug: erlotinib hydrochloride

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

NIH

Identifiers

NCT00077454

NCI-04-C-0256

NCI-2012-01808

COG-ADVL0214

ADVL0214

CDR0000350336

U01CA097452 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

95 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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