Bortezomib in Treating Children With Advanced Solid Tumors

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Unspecified Childhood Solid Tumor, Protocol Specific

Treatments

Other: laboratory biomarker analysis

Drug: bortezomib

Other: pharmacological study

Study type

Interventional

Funder types

NIH

Identifiers

NCT00021216

COG-ADVL0015

NCI-2012-01860 (Registry Identifier)

ADVL0015 (Other Identifier)

CDR0000068760

U01CA097452 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of bortezomib in treating children who have advanced solid tumors that have not responded to previous treatment.

Full description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of bortezomib in pediatric patients with refractory solid tumors.

II. Determine the dose-limiting toxicity and other toxic effects of this regimen in these patients.

III. Preliminarily determine the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib 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. If dose-limiting toxicity in the form of myelosuppression occurs in stratum I, dose escalation continues with patients meeting the qualifications for stratum II.

PROJECTED ACCRUAL: Approximately 24-36 patients will be accrued for this study.

Enrollment

36 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Histologically confirmed solid tumor that is refractory to standard therapy or for which no standard therapy exists
- Histologic confirmation not required for brainstem glioma or optic pathway tumor
Ineligible for therapies of higher priority
Stratum II only:
- No bone marrow involvement
Performance status - Karnofsky 50-100% (over 10 years of age)
Performance status - Lansky 50-100% (10 years of age and under)
At least 8 weeks
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 75,000/mm^3 (transfusion independent)
Hemoglobin at least 8 g/dL (RBC transfusions allowed)
Bilirubin less than 1.5 mg/dL
ALT less than 5 times normal for age
Albumin at least 2 g/dL
Creatinine no greater than upper limit of normal for age
Creatinine clearance or radioisotope glomerular filtration rate greater than 70 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Neurologic deficits related to CNS tumors allowed if relatively stable for at least 2 weeks
No uncontrolled infection
At least 7 days since prior biologic therapy and recovered
At least 3 months since prior allogeneic stem cell transplantation
At least 1 week since prior growth factors
Stratum II only:
- No prior stem cell transplantation with or without total body irradiation
At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) and recovered
Stratum II only:
- No more than 2 prior multi-agent chemotherapy regimens
- More than 2 single-agent regimens allowed
Concurrent dexamethasone allowed for CNS tumors if stable dose for at least 2 weeks
See Biologic therapy
At least 2 weeks since prior palliative local radiotherapy
At least 6 months since prior craniospinal radiotherapy or radiotherapy to at least 50% of pelvis
At least 6 weeks since prior substantial bone marrow radiotherapy
Recovered from prior radiotherapy
Stratum II only:
- No prior radiotherapy to more than 20% of bone marrow
No prior bortezomib
No concurrent anticonvulsants
No other concurrent investigational agents