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A Phase I Study Of PS-341 In Pediatric Patients With Refractory Solid Tumors

Phase 1
21 Years
Open (Enrolling)
Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study Of PS-341 In Pediatric Patients With Refractory Solid Tumors


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

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.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD defined as the dose at which fewer than 20% of patients experience DLT assessed using CTC version 2.0

Outcome Time Frame:

3 weeks

Safety Issue:


Principal Investigator

Susan Blaney

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

November 2001

Completion Date:

Related Keywords:

  • Unspecified Childhood Solid Tumor, Protocol Specific
  • Neoplasms



Children's Oncology Group Arcadia, California  91006-3776