Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01638533|
Recruitment Status : Active, not recruiting
First Posted : July 11, 2012
Last Update Posted : May 6, 2019
|Condition or disease||Intervention/treatment||Phase|
|Glioma Lymphoma Metastatic Malignant Solid Neoplasm Neuroendocrine Neoplasm Recurrent Adult Soft Tissue Sarcoma Recurrent Bladder Carcinoma Recurrent Breast Carcinoma Recurrent Chronic Lymphocytic Leukemia Recurrent Colorectal Carcinoma Recurrent Head and Neck Carcinoma Recurrent Lung Carcinoma Recurrent Malignant Solid Neoplasm Recurrent Melanoma Recurrent Pancreatic Carcinoma Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma Recurrent Prostate Carcinoma Recurrent Renal Cell Carcinoma Recurrent Thyroid Gland Carcinoma Refractory Chronic Lymphocytic Leukemia Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma Stage III Breast Cancer AJCC v7 Stage III Colorectal Cancer AJCC v7 Stage III Cutaneous Melanoma AJCC v7 Stage III Lung Cancer AJCC v7 Stage III Pancreatic Cancer AJCC v6 and v7 Stage III Prostate Cancer AJCC v7 Stage III Renal Cell Cancer AJCC v7 Stage III Soft Tissue Sarcoma AJCC v7 Stage IIIA Breast Cancer AJCC v7 Stage IIIA Colorectal Cancer AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Breast Cancer AJCC v7 Stage IIIB Colorectal Cancer AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Breast Cancer AJCC v7 Stage IIIC Colorectal Cancer AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Breast Cancer AJCC v6 and v7 Stage IV Colorectal Cancer AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Stage IV Lung Cancer AJCC v7 Stage IV Pancreatic Cancer AJCC v6 and v7 Stage IV Prostate Cancer AJCC v7 Stage IV Renal Cell Cancer AJCC v7 Stage IV Soft Tissue Sarcoma AJCC v7 Stage IVA Colorectal Cancer AJCC v7 Stage IVB Colorectal Cancer AJCC v7 Unresectable Solid Neoplasm||Other: Pharmacological Study Drug: Romidepsin||Phase 1|
I. To establish the safety and tolerability of romidepsin given on days 1, 8, and 15 of a 28 day cycle to patients with varying degrees of liver dysfunction (mild, moderate and severe).
II. To establish the maximum tolerated dose (MTD) and appropriate dosing recommendations for romidepsin in such patients.
III. To characterize the pharmacokinetics (PK) of romidepsin in patients with varying degrees of liver dysfunction.
I. To explore correlations of the Child-Pugh classification of liver dysfunction with the observed toxicities and plasma PK of romidepsin administration.
II. To document any preliminary evidence of antitumor activity at tolerable doses of romidepsin in patients with varying degrees of liver dysfunction.
OUTLINE: This is a dose-escalation study.
Patients receive romidepsin intravenously (IV) over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 and Pharmacokinetic Single Agent Study of Romidepsin in Patients With, Lymphomas, Chronic Lymphocytic Leukemia, and Select Solid Tumors and Varying Degrees of Liver Dysfunction|
|Actual Study Start Date :||June 12, 2012|
|Actual Primary Completion Date :||November 29, 2018|
Experimental: Treatment (romidepsin)
Patients receive romidepsin IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Pharmacological Study
- Maximum tolerated dose of romidepsin in groups of patients with varying degree of hepatic dysfunction according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0 [ Time Frame: 28 days ]Analyses will be descriptive in nature. The observed toxicities will be characterized by dose level within each category of liver dysfunction (mild, moderate, severe, and liver transplant). These results will be summarized in relation to what is known about romidepsin in a population without liver dysfunction (as defined in this protocol).
- Dose-limiting toxicity of romidepsin in groups of patients with varying degree of hepatic dysfunction according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0 [ Time Frame: 28 days ]In order to define levels of hepatic impairment at which dose modifications of romidepsin are required, data will be combined across hepatic dysfunction groups to evaluate the association between toxicity, dose, and liver assay level(s). The outcome variable, drug tolerance and dose-limiting toxicities will be modeled as function of dose and liver assay using multivariate linear regression. Higher order terms of the predictor variables and interactions will be included if there is evidence of non-linear and/or non-additive associations.
- Pharmacokinetic (PK) profile of romidepsin in patients with varying degrees of hepatic dysfunction using liquid chromatography-electrospray ionization tandem mass spectrometric method [ Time Frame: 0, 1, 2, 3, 4, 4.25, 4.5, 5, 6, 8, 10, 24, and 48 hours after initiation of the infusion on day 1 ]Pharmacokinetic variables will be tabulated and descriptive statistics calculated for each function group. Geometric means and coefficients of variation will be presented for maximum concentration and area under the curve for each group.
- Child-Pugh classification of hepatic dysfunction [ Time Frame: Baseline ]Correlations of the Child-Pugh classification of hepatic dysfunction with the observed toxicities and plasma PK of romidepsin administration will be explored.
- Antitumor activity assessed using Response Evaluation Criteria in Solid Tumors and the International Workshop Lymphoma Response Criteria [ Time Frame: Up to 30 days ]Association of antitumor activity and romidepsin treatment will be documented.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01638533
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Georgia|
|Emory University Hospital/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center|
|Baltimore, Maryland, United States, 21287|
|National Cancer Institute Developmental Therapeutics Clinic|
|Bethesda, Maryland, United States, 20892|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|Thomas Jefferson University Hospital|
|Philadelphia, Pennsylvania, United States, 19107|
|University Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Roisin M Connolly||JHU Sidney Kimmel Comprehensive Cancer Center LAO|