search
Back to results

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

Primary Purpose

Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Kidney Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
carboplatin
talabostat mesylate
temozolomide
pharmacological study
Sponsored by
National Institutes of Health Clinical Center (CC)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring unspecified childhood solid tumor, protocol specific, recurrent childhood rhabdomyosarcoma, recurrent childhood soft tissue sarcoma, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent osteosarcoma, recurrent neuroblastoma, recurrent Wilms tumor and other childhood kidney tumors, recurrent childhood malignant germ cell tumor, recurrent childhood liver cancer, recurrent childhood brain stem glioma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood ependymoma, recurrent childhood medulloblastoma, recurrent childhood supratentorial primitive neuroectodermal tumor, childhood atypical teratoid/rhabdoid tumor, childhood low-grade cerebral astrocytoma, childhood high-grade cerebral astrocytoma, childhood choroid plexus tumor, childhood craniopharyngioma, childhood infratentorial ependymoma, childhood supratentorial ependymoma, childhood oligodendroglioma, recurrent childhood visual pathway and hypothalamic glioma, recurrent childhood brain tumor, childhood central nervous system germ cell tumor, childhood grade I meningioma, childhood grade II meningioma, childhood grade III meningioma, childhood malignant ovarian germ cell tumor, childhood malignant testicular germ cell tumor, childhood teratoma

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed solid tumors, including, but not limited to, any of the following: Rhabdomyosarcoma and other soft tissue sarcomas Ewing's sarcoma family of tumors Osteosarcoma Neuroblastoma Wilms' tumor Hepatic tumors Germ cell tumors Primary brain tumors In patients with brainstem or optic gliomas, requirement for histological confirmation can be waived if biopsy was not performed Patients with brainstem gliomas that did not respond to therapy but that are without radiographic evidence of disease progression must have clinical evidence of progression Patients with brain tumors must be on stable or tapering dose of corticosteroids for 7 days prior to study entry Measurable or evaluable disease Relapsed or failed to respond to frontline curative therapy, including any of the following: Surgery Radiotherapy Chemotherapy Combination of modalities No other potentially curative treatment options available PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Hemoglobin ≥ 8 mg/dL Platelet count ≥ 100,000/mm^3 (platelet transfusion independent) Bilirubin ≤ 1.5 times upper limit of normal (ULN) SGPT ≤ 2.5 times ULN Creatinine clearance ≥ 60 mL/min OR age-adjusted creatinine* as follows: No more than 0.8 mg/dL (for patients ≤ 5 years of age) No more than 1.0 mg/dL (for patients 6 to 10 years of age) No more than 1.2 mg/dL (for patients 11 to 15 years of age) No more than 1.5 mg/dL (for patients > 15 years of age) NOTE: *For patients receiving carboplatin a nuclear glomerular filtration rate study, 24-hour urine collection, and serum creatinine for estimation of creatinine clearance is required if under 15 years of age OR serum creatinine and weight for estimation of creatinine clearance is required if 15-18 years of age Patients with history of seizures eligible if seizures controlled by anticonvulsants 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

Sites / Locations

  • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
March 15, 2006
Last Updated
March 14, 2012
Sponsor
National Institutes of Health Clinical Center (CC)
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00303940
Brief Title
Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors
Official Title
A Phase I Trial and Pharmacokinetic Study of Talabostat (PT-100, Val-Boro-Pro) in Combination With Temozolomide or Carboplatin in Pediatric Patients With Relapsed or Refractory Solid Tumors Including Brain Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
National Institutes of Health Clinical Center (CC)
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Kidney Cancer, Liver Cancer, Neuroblastoma, Ovarian Cancer, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific
Keywords
unspecified childhood solid tumor, protocol specific, recurrent childhood rhabdomyosarcoma, recurrent childhood soft tissue sarcoma, recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor, recurrent osteosarcoma, recurrent neuroblastoma, recurrent Wilms tumor and other childhood kidney tumors, recurrent childhood malignant germ cell tumor, recurrent childhood liver cancer, recurrent childhood brain stem glioma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, recurrent childhood ependymoma, recurrent childhood medulloblastoma, recurrent childhood supratentorial primitive neuroectodermal tumor, childhood atypical teratoid/rhabdoid tumor, childhood low-grade cerebral astrocytoma, childhood high-grade cerebral astrocytoma, childhood choroid plexus tumor, childhood craniopharyngioma, childhood infratentorial ependymoma, childhood supratentorial ependymoma, childhood oligodendroglioma, recurrent childhood visual pathway and hypothalamic glioma, recurrent childhood brain tumor, childhood central nervous system germ cell tumor, childhood grade I meningioma, childhood grade II meningioma, childhood grade III meningioma, childhood malignant ovarian germ cell tumor, childhood malignant testicular germ cell tumor, childhood teratoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
26 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Type
Drug
Intervention Name(s)
talabostat mesylate
Intervention Type
Drug
Intervention Name(s)
temozolomide
Intervention Type
Other
Intervention Name(s)
pharmacological study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed solid tumors, including, but not limited to, any of the following: Rhabdomyosarcoma and other soft tissue sarcomas Ewing's sarcoma family of tumors Osteosarcoma Neuroblastoma Wilms' tumor Hepatic tumors Germ cell tumors Primary brain tumors In patients with brainstem or optic gliomas, requirement for histological confirmation can be waived if biopsy was not performed Patients with brainstem gliomas that did not respond to therapy but that are without radiographic evidence of disease progression must have clinical evidence of progression Patients with brain tumors must be on stable or tapering dose of corticosteroids for 7 days prior to study entry Measurable or evaluable disease Relapsed or failed to respond to frontline curative therapy, including any of the following: Surgery Radiotherapy Chemotherapy Combination of modalities No other potentially curative treatment options available PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,500/mm^3 Hemoglobin ≥ 8 mg/dL Platelet count ≥ 100,000/mm^3 (platelet transfusion independent) Bilirubin ≤ 1.5 times upper limit of normal (ULN) SGPT ≤ 2.5 times ULN Creatinine clearance ≥ 60 mL/min OR age-adjusted creatinine* as follows: No more than 0.8 mg/dL (for patients ≤ 5 years of age) No more than 1.0 mg/dL (for patients 6 to 10 years of age) No more than 1.2 mg/dL (for patients 11 to 15 years of age) No more than 1.5 mg/dL (for patients > 15 years of age) NOTE: *For patients receiving carboplatin a nuclear glomerular filtration rate study, 24-hour urine collection, and serum creatinine for estimation of creatinine clearance is required if under 15 years of age OR serum creatinine and weight for estimation of creatinine clearance is required if 15-18 years of age Patients with history of seizures eligible if seizures controlled by anticonvulsants 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Holly Meany, MD
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Elizabeth Fox, MD
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892-1182
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20460632
Citation
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.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs