Talabostat in Treating Patients With Metastatic Kidney Cancer

Study Overview
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Brief Summary
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RATIONALE: Talabostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well talabostat works in treating patients with metastatic kidney cancer.

Detailed Description
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OBJECTIVES: Primary Determine the response rate in patients with metastatic renal cell carcinoma treated with talabostat mesylate. Determine the progression-free survival of patients treated with this drug. Secondary Determine the toxicity of this drug in these patients. Correlate changes in specific cytokine levels and peripheral blood flow cytometry with progression-free survival. OUTLINE: This is a nonrandomized study. Patients receive oral talabostat mesylate once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Blood samples are obtained from patients at baseline and after each course for biomarker correlative studies. Samples are analyzed for serum cytokines and chemokines and for T-cell subsets and natural killer (NK) cells by flow cytometry. Peripheral blood lymphocytes are obtained at baseline and after course 1 for future assessment by gene microarray analysis.

Official Title
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A Phase II Study of Talabostat in Patients With Metastatic Renal Cell Carcinoma

Conditions
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Kidney Cancer

Intervention / Treatment
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* Drug: talabostat mesylate
* Biological: enzyme inhibitor therapy
* Diagnostic Test: flow cytometry
* Diagnostic Test: laboratory biomarker analysis
* Biological: non-specific immune-modulator therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Pathologic diagnosis of renal cell carcinoma (clinical confirmation of metastatic disease required) Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan Progressed after ≥ 1 multikinase inhibitor regimen (i.e., sorafenib tosylate or sunitinib malate) No history of central nervous system or brain metastasis Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Absolute neutrophil count (ANC) ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 8.5 g/dL (no packed red blood cell transfusions within the past 4 weeks) (epoetin alfa support allowed) Bilirubin ≤ 1.5 times the upper limit of normal (ULN) (unless due to Gilbert's syndrome) aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 3 times ULN Creatinine < 2.0 mg/dL No active serious infections No other malignancy within the past 5 years except basal cell or nonmetastatic squamous cell skin cancer or carcinoma in situ of the cervix No comorbidity or concurrent condition that would interfere with protocol assessments or procedures No ongoing coagulopathy At least 4 weeks since prior systemic therapy and recovered Prior radiotherapy allowed as long as the lesion treated is not used to assess response No prior radiotherapy to > 50% of the bone marrow No prior radiotherapy to index lesions unless there is clearly progressive disease within the irradiated area OR measurable disease outside the irradiated area Exclusion Criteria History of CNS or brain metastasis Pregnant, nursing or planning on becoming pregnant Active serious infections Malignancy within the past 5 years except basal cell or nonmetastatic squamous cell skin cancer or carcinoma in situ of the cervix comorbidity or concurrent condition that would interfere with protocol assessments or procedures

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Talabostat<br>Talabostat 600 mcg orally, daily x 14 days (21 day cycle); 2 cycles | Drug: talabostat mesylate<br> <br> * Other names: Val-boroPro;Biological: enzyme inhibitor therapy<br> <br> Diagnostic Test: flow cytometry<br> <br> Diagnostic Test: laboratory biomarker analysis<br> <br> Biological: non-specific immune-modulator therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Evaluable patients are those that have completed 4 cycles of treatment. | After 9 and 12 evaluable patients (126 to 168 days of total treatment). Each course is 14 days and repeats every 21 days in the absence of disease progression or unacceptable toxicity. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity | Any grade 3-4 non-haematological or grade 4 haematological toxicity at least possibly related to treatment | From day 1 through 14 of each course. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | 
| Adverse events | Adverse events as assessed by NCI CTCAE v3.0 | From day 1 through 14 of each course. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV renal cell cancer, recurrent renal cell cancer