Bortezomib in Treating Children With Advanced Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Childhood Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: bortezomib

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Arcadia, California, United States, 91006-3776
      • Children's Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (bortezomib); 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.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: bortezomib; Given IV; Other Names: MLN341; LDP 341; VELCADE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival		Up to 24 months
MTD defined as the dose at which fewer than 20% of patients experience DLT assessed using CTC version 2.0		3 weeks
20S proteasome inhibition	The 95% confidence interval for the percent of patients who exhibit inhibition at a recommended dose level determined according to the table above is 61%-100%, if six patients are evaluated or 55%-100% if five patients are evaluated.	Up to 2 weeks

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Susan Blaney, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start: November 1, 2001
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: July 11, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): April 15, 2015
• Last Update Submitted That Met QC Criteria: April 14, 2015
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: NCI-2012-01860 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U01CA097452 (U.S. NIH Grant/Contract); COG-ADVL0015; CDR0000068760; ADVL0015 (Other Identifier: CTEP)