Digestive System Diseases

All Conditions

Liver Diseases

Gastrointestinal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Bortezomib

Liver Extracts

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

bortezomib

pharmacological study

Patricia LoRusso

Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. This phase I trial is studying the side effects and best dose of bortezomib in treating patients with advanced cancer and liver dysfunction.

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of bortezomib in patients with advanced malignancies and varying degrees of liver dysfunction.

II. Determine the safety and tolerability of this drug in these patients. III. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients with mild, moderate, or severe liver insufficiency.

IV. Examine the dietary influences on bortezomib disposition and efficacy. V. Examine the influences of proteasome inhibition on CYP 450 activity.

OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to hepatic function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction).

Patients receive bortezomib IV over 3-5 seconds 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 per stratum 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 6 patients experience dose-limiting toxicity.

\[Note: Patients with normal hepatic function do not receive escalating doses of bortezomib.\]

Bortezomib in Treating Patients With Advanced Cancer and Liver Dysfunction

A Phase I Pharmacokinetic Study of PS-341 in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction for the CTEPSponsored Organ Dysfunction Working Group

National Cancer Institute (NCI)

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Anti-Infective Agents

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of temsirolimus 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. Up to 12 patients are treated at the MTD.

temsirolimus

laboratory biomarker analysis

John Sarantopoulos

This phase I trial is studying the side effects and best dose of temsirolimus in treating patients with metastatic solid tumor or lymphoma that cannot be removed by surgery who have different levels of liver function. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Temsirolimus may have different effects in patients who have changes in their liver function

PRIMARY OBJECTIVES:

I. To evaluate the safety, tolerability, and to establish the maximum tolerated recommended dose (RD) CCI-779 (temsirolimus) in cohorts of patients with varying degrees of hepatic dysfunction (mild, moderate, and severe) in order to provide appropriate dosing recommendations for CCI-779 (temsirolimus) in this population.

SECONDARY OBJECTIVES:

I. To characterize the pharmacokinetic (PK) profile of CCI-779 (temsirolimus) in patients with varying degrees of hepatic function.

II. To determine if the pharmacodynamic (PD) profile of CCI-779 (temsirolimus) as measured by drug effects on p70s6 kinase and p4EBP1 phosphorylation and other markers of mTOR inhibition in peripheral blood mononuclear cells (PBMC) is altered in patients with varying degrees of hepatic function.

III. To document the non-dose limiting toxicities and any anti-tumor efficacy associated with administration of CCI-779 (temsirolimus) in this patient population.

IV. To compare the NCI ODWG criteria and the Child-Pugh classification of hepatic dysfunction in terms of their predictive value in reducing interpatient variability in the PK and PD of CCI-779 (temsirolimus).

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to hepatic function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction vs liver transplant).

Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of temsirolimus 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. Up to 12 patients are treated at the MTD.

After completion of study treatment, patients are followed periodically for 30 days.

Temsirolimus in Treating Patients With Metastatic Solid Tumor or Lymphoma That Cannot Be Removed By Surgery Who Have Different Levels of Liver Function

A Phase I Pharmacokinetic and Pharmacodynamic Study of Temsirolimus (CCI-779) in Patients With Advanced Malignancies and Normal and Impaired Liver Function: An NCI Organ Dysfunction Working Group Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bortezomib in Treating Patients With Advanced Cancer and Liver Dysfunction	NCT00091117	Hepatic Complic... Malignant Neopl...	bortezomib pharmacological...	18 Years -	National Cancer Institute (NCI)
Temsirolimus in Treating Patients With Metastatic Solid Tumor or Lymphoma That Cannot Be Removed By Surgery Who Have Different Levels of Liver Function	NCT00275093	Hepatic Complic... Lymphoma Unspecified Adu...	temsirolimus laboratory biom... pharmacological...	18 Years -	National Cancer Institute (NCI)
Temsirolimus in Treating Patients With Metastatic Solid Tumor or Lymphoma That Cannot Be Removed By Surgery Who Have Different Levels of Liver Function	NCT00275093	Hepatic Complic... Lymphoma Unspecified Adu...	temsirolimus laboratory biom... pharmacological...	18 Years -	National Cancer Institute (NCI)
Bortezomib in Treating Patients With Advanced Cancer and Liver Dysfunction	NCT00091117	Hepatic Complic... Malignant Neopl...	bortezomib pharmacological...	18 Years -	National Cancer Institute (NCI)

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