Bortezomib in Treating Children With Advanced Solid Tumors - Full Text View

Purpose

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.

Condition	Intervention	Phase
Unspecified Childhood Solid Tumor, Protocol Specific	Drug: bortezomib Other: laboratory biomarker analysis Other: pharmacological study	Phase 1


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Study Of PS-341 In Pediatric Patients With Refractory Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Bortezomib

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

MTD defined as the dose at which fewer than 20% of patients experience DLT assessed using CTC version 2.0 [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
20S proteasome inhibition [ Time Frame: Up to 2 weeks ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]


Enrollment:	36
Study Start Date:	November 2001
Study Completion Date:	December 2005
Primary Completion Date:	December 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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

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.

Eligibility


Ages Eligible for Study:	up to 21 Years (Child, Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00021216

Locations


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

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Susan Blaney	Children's Oncology Group

More Information


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00021216 History of Changes
Other Study ID Numbers:	NCI-2012-01860 NCI-2012-01860 COG-ADVL0015 CDR0000068760 ADVL0015 ADVL0015 U01CA097452
Study First Received:	July 11, 2001
Last Updated:	April 14, 2015
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Bortezomib Antineoplastic Agents

ClinicalTrials.gov processed this record on September 28, 2016