Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors

NCT ID: NCT00303940

Last Updated: 2012-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2010-02-28

Brief Summary

RATIONALE: Talabostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving talabostat together with temozolomide or carboplatin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of talabostat when given together with temozolomide or carboplatin in treating young patients with relapsed or refractory brain tumors or other solid tumors.

Detailed Description

OBJECTIVES:

Primary

• Determine the dose of talabostat, when used in combination with either temozolomide or carboplatin, at which maximum plasma dipeptidyl peptidase IV enzyme inhibition is achieved (in the absence of talabostat-related dose-limiting toxicity) in pediatric patients with refractory or relapsed solid tumors, including brain tumors.
• Determine the maximum tolerated dose of talabostat, when used in combination with temozolomide or carboplatin in pediatric patients, if dose-limiting toxicity attributed to talabostat is observed.
• Define the toxicity profile of talabostat when used in combination with temozolomide or carboplatin.
• Describe the pharmacokinetic profile of talabostat in pediatric patients.

Secondary

• Study levels, at baseline and after drug administration, of serum cytokines (interleukin [IL]-2, IL-6, IL-10, filgrastim [G-CSF], tumor necrosis factor-α, IL-1β, IL-8, IP10, and thrombospondin) that may be important in the immune-mediated antitumor effect of talabostat.
• Evaluate the antitumor effect of talabostat in combination with temozolomide or carboplatin on pediatric solid tumors by direct assessment of tumor response.
• Study the effect of talabostat on neutrophil function.
• Evaluate the expression of fibroblast activation protein (FAP) in pediatric tumors using immunohistochemistry to detect FAP in paraffin-embedded tissue sections from existing tumor specimens, when available.

OUTLINE: This is a dose-escalation study of talabostat. Patients are stratified according to tumor histology and prior therapy.

Based on stratification, patients receive either oral temozolomide on days 1-5 or carboplatin IV over 30 minutes on days 1-2. Patients also receive oral talabostat on days 7-20. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. (Closed to accrual as of 5/25/2009)

Cohorts of 2-6 patients receive escalating doses of talabostat until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or < 4 of 12 patients experience dose-limiting toxicity during the first course of therapy.

PROJECTED ACCRUAL: A total of 26 patients will be accrued for this study.

Conditions

Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Kidney Cancer; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Study Design

• Primary Study Purpose: TREATMENT

Interventions

carboplatin

Intervention Type: DRUG

talabostat mesylate

Intervention Type: DRUG

temozolomide

Intervention Type: DRUG

pharmacological study

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• No clinically significant, unrelated systemic illness, including either of the following:

• Serious infections
• Hepatic, renal, or other organ dysfunction that would preclude study treatment
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No generalized pitting peripheral edema
• No sensitivity to valine-proline boronic acid

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered to ≤ grade 1 from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study entry
• Any number of prior chemotherapy regimens allowed
• Prior temozolomide or carboplatin as frontline therapy or in the adjuvant setting allowed provided patient did not experience severe toxicities related to the drug and tumor progressed during this therapy
• At least 3 weeks since last dose of all myelosuppressive chemotherapy
• At least 7 days since last dose of anticancer biologic agents (e.g., retinoids)
• At least 30 days since prior investigational agents
• At least 4 weeks since prior radiotherapy to > 25% of marrow-containing bones (pelvis, spine, or skull) (2 weeks for palliative [limited-port] radiotherapy)
• At least 2 months since prior autologous stem cell transplantation and recovered
• At least 1 week since prior filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa
• At least 2 weeks since prior pegfilgrastim
• No history of allogeneic stem cell transplantation
• No other concurrent anticancer chemotherapy, radiation therapy, or immunotherapy
• No other concurrent investigational agents

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role: lead

Principal Investigators

Holly Meany, MD

Role: STUDY_CHAIR

National Cancer Institute (NCI)

Elizabeth Fox, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

Countries

United States

References

Meany H, Balis FM, Aikin A, Whitcomb P, Murphy RF, Steinberg SM, Widemann BC, Fox E. Pediatric phase I trial design using maximum target inhibition as the primary endpoint. J Natl Cancer Inst. 2010 Jun 16;102(12):909-12. doi: 10.1093/jnci/djq174. Epub 2010 May 11.

Reference Type: RESULT

PMID: 20460632 (View on PubMed)

Other Identifiers

05-C-0239

Identifier Type: -

Identifier Source: secondary_id

NCI-P6672

Identifier Type: -

Identifier Source: secondary_id

CDR0000462620

Identifier Type: -

Identifier Source: secondary_id

050239

Identifier Type: -

Identifier Source: org_study_id

NCT00261885

Identifier Type: -

Identifier Source: nct_alias