Protocol Number: 05-C-0239

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

Number:

05-C-0239

Summary:

This study will determine the safe dose and potential benefit of the experimental drug Talabostat, together with either temozolomide or carboplatin, for treating children and adolescents with solid tumor cancers. Temozolomide and carboplatin are standard anti-cancer drugs used to treat children. Talabostat, a drug developed to stimulate the recovery of normal blood cells after chemotherapy, was found to enhance the anti-cancer effects of chemotherapy in animal models. The study will also examine how the body handles Talabostat and how it may affect various proteins and cells in the body.

Patients between 2 and 18 years of age with solid tumors whose disease has failed to respond to treatment with standard curative therapies or has relapsed after treatment and for whom no other potentially curative therapy is available may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests and radiological evaluations, such as computed tomography (CT) scans and magnetic resonance imaging (MRI), to measure the extent of disease.

Participants receive drug therapy in 28-week cycles. They are assigned to take either temozolomide or carboplatin, depending on their type of cancer and what drugs they have previously received. Temozolomide is taken by mouth, in tablet form, on days 1 through 5 of each treatment cycle. Carboplatin is given intravenously (into a vein) on days 1 and 2 of each treatment cycle. Talabostat is taken by mouth, in tablet form, once a day starting on day 7 of the treatment cycle and continuing 14 days. The dose of Talabostat is increased incrementally in small groups of patients until unacceptable toxicity occurs or until a blood test shows that the drug has completely blocked a protein in the blood called DPP-IV in at least 5 or 6 patients treated at a given dose level. (When DPP-IV is blocked, it is a marker that the dose is effective.) An additional 12 patients are then given a slightly higher dose of Talabostat, as long as serious side effects do not occur in more than one patient, to increase the certainty that the DPP-IV is completely blocked in all patients.

During the first treatment cycle, several special varying blood tests are conducted to see how the body handles Talabostat; to examine the drug's effects on the body; study DPP-IV activity; examine the function of infection-fighting white blood cells called neutrophils; and study immune-stimulating proteins called cytokines. Patients also are examined by a physician once a week and have blood drawn twice a week. Each tumor is evaluated by MRI or CT scans before starting therapy and after every two treatment cycles. A tumor sample collected during a prior surgery or biopsy is examined for the presence of fibroblast activation protein (FAP), an enzyme that is blocked by Talabostat and may be important in the drug's effect on tumors.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Childhood Cancer

Toxicity

DPP-IV

Dose Response

Cytokines

Recruitment Keyword(s):

Pediatrics

Solid Tumor

Brain Tumor

Childhood Cancer

Condition(s):

Relapsed or Refractory Solid Tumors

Brain Tumor

Investigational Drug(s):

Talabostat

Investigational Device(s):

None

Interventions:

Drug: Talabostat

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Overexpression of thrombospondin-1 decreases angiogenesis and inhibits the growth of human cutaneous squamous cell carcinomas. Am J Pathol. 1999 Aug;155(2):441-52.

Adams S, Miller GT, Jesson MI, Watanabe T, Jones B, Wallner BP. Related Articles, Links PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism. Cancer Res. 2004 Aug 1;64(15):5471-80.

Garin-Chesa P, Old LJ, Rettig WJ. Related Articles, Links Cell surface glycoprotein of reactive stromal fibroblasts as a potential antibody target in human epithelial cancers. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7235-9.

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