Bortezomib in Treating Children With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT00021216
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: April 15, 2015
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: July 11, 2001
• First Posted Date: January 27, 2003
• Last Update Posted Date: April 15, 2015
• Study Start Date: November 2001
• Actual Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 15, 2013)

• MTD defined as the dose at which fewer than 20% of patients experience DLT assessed using CTC version 2.0 [ Time Frame: 3 weeks ]
• 20S proteasome inhibition [ Time Frame: Up to 2 weeks ]
  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.
• Progression free survival [ Time Frame: Up to 24 months ]

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Bortezomib in Treating Children With Advanced Solid Tumors
• Official Title: A Phase I Study Of PS-341 In Pediatric Patients With Refractory Solid Tumors
• Brief Summary: 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.

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
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

• Drug: bortezomib
  Given IV
  Other Names:

  • LDP 341
  • MLN341
  • VELCADE
• Other: laboratory biomarker analysis
  Correlative studies
• Other: pharmacological study
  Correlative studies
  Other Name: pharmacological studies

Study Arms

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.

Interventions:

• Drug: bortezomib
• Other: laboratory biomarker analysis
• Other: pharmacological study

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 15, 2013): 36
• Original Enrollment: Not Provided
• Actual Study Completion Date: December 2005
• Actual Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States
• Removed Location Countries: Australia, Canada

Administrative Information

• NCT Number: NCT00021216
• Other Study ID Numbers: NCI-2012-01860; NCI-2012-01860 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); COG-ADVL0015; CDR0000068760; ADVL0015 ( Other Identifier: Children's Oncology Group ); ADVL0015 ( Other Identifier: CTEP ); U01CA097452 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Cancer Institute (NCI)
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Cancer Institute (NCI)
• Original Study Sponsor: Children's Oncology Group
• Collaborators: Not Provided

Investigators

• Principal Investigator: Susan Blaney; Children's Oncology Group

• PRS Account: National Cancer Institute (NCI)
• Verification Date: December 2013