Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01638533
First received: July 9, 2012
Last updated: September 16, 2014
Last verified: August 2014
  Purpose

This phase I trial studies the side effects and best dose of romidepsin in treating patients with lymphoma, chronic lymphocytic leukemia, or solid tumors with liver dysfunction. Romidepsin may stop the growth of cancer cells by entering the cancer cells and by blocking the activity of proteins that are important for the cancer's growth and survival.


Condition Intervention Phase
Adult Anaplastic Astrocytoma
Adult Anaplastic Ependymoma
Adult Anaplastic Oligodendroglioma
Adult Brain Stem Glioma
Adult Ependymoblastoma
Adult Giant Cell Glioblastoma
Adult Glioblastoma
Adult Gliosarcoma
Adult Mixed Glioma
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Adult Pineal Gland Astrocytoma
AIDS-related Diffuse Large Cell Lymphoma
AIDS-related Diffuse Mixed Cell Lymphoma
AIDS-related Diffuse Small Cleaved Cell Lymphoma
AIDS-related Immunoblastic Large Cell Lymphoma
AIDS-related Lymphoblastic Lymphoma
AIDS-related Peripheral/Systemic Lymphoma
AIDS-related Primary CNS Lymphoma
AIDS-related Small Noncleaved Cell Lymphoma
Anaplastic Large Cell Lymphoma
Anaplastic Thyroid Cancer
Angioimmunoblastic T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extensive Stage Small Cell Lung Cancer
Extra-adrenal Paraganglioma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Gastrinoma
Glucagonoma
Hepatic Complications
Hepatosplenic T-cell Lymphoma
HIV-associated Hodgkin Lymphoma
Insular Thyroid Cancer
Insulinoma
Intraocular Lymphoma
Male Breast Cancer
Metastatic Gastrointestinal Carcinoid Tumor
Metastatic Pheochromocytoma
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Pancreatic Polypeptide Tumor
Peripheral T-cell Lymphoma
Pulmonary Carcinoid Tumor
Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Brain Tumor
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult Soft Tissue Sarcoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Basal Cell Carcinoma of the Lip
Recurrent Bladder Cancer
Recurrent Breast Cancer
Recurrent Colon Cancer
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Recurrent Gastrointestinal Carcinoid Tumor
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Recurrent Islet Cell Carcinoma
Recurrent Lymphoepithelioma of the Nasopharynx
Recurrent Lymphoepithelioma of the Oropharynx
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Melanoma
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Recurrent Mucoepidermoid Carcinoma of the Oral Cavity
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Neuroendocrine Carcinoma of the Skin
Recurrent Non-small Cell Lung Cancer
Recurrent Pancreatic Cancer
Recurrent Pheochromocytoma
Recurrent Prostate Cancer
Recurrent Rectal Cancer
Recurrent Renal Cell Cancer
Recurrent Salivary Gland Cancer
Recurrent Small Cell Lung Cancer
Recurrent Small Lymphocytic Lymphoma
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Squamous Cell Carcinoma of the Larynx
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Oropharynx
Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Recurrent Thyroid Cancer
Recurrent Verrucous Carcinoma of the Larynx
Recurrent Verrucous Carcinoma of the Oral Cavity
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Regional Gastrointestinal Carcinoid Tumor
Regional Pheochromocytoma
Small Intestine Lymphoma
Somatostatinoma
Splenic Marginal Zone Lymphoma
Stage III Adenoid Cystic Carcinoma of the Oral Cavity
Stage III Adult Soft Tissue Sarcoma
Stage III Basal Cell Carcinoma of the Lip
Stage III Bladder Cancer
Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage III Follicular Thyroid Cancer
Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage III Lymphoepithelioma of the Nasopharynx
Stage III Lymphoepithelioma of the Oropharynx
Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage III Mucoepidermoid Carcinoma of the Oral Cavity
Stage III Neuroendocrine Carcinoma of the Skin
Stage III Pancreatic Cancer
Stage III Papillary Thyroid Cancer
Stage III Prostate Cancer
Stage III Renal Cell Cancer
Stage III Salivary Gland Cancer
Stage III Squamous Cell Carcinoma of the Hypopharynx
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage III Squamous Cell Carcinoma of the Nasopharynx
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage III Verrucous Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Oral Cavity
Stage IIIA Breast Cancer
Stage IIIA Colon Cancer
Stage IIIA Melanoma
Stage IIIA Non-small Cell Lung Cancer
Stage IIIA Rectal Cancer
Stage IIIB Breast Cancer
Stage IIIB Colon Cancer
Stage IIIB Melanoma
Stage IIIB Non-small Cell Lung Cancer
Stage IIIB Rectal Cancer
Stage IIIC Breast Cancer
Stage IIIC Colon Cancer
Stage IIIC Melanoma
Stage IIIC Rectal Cancer
Stage IV Adult Soft Tissue Sarcoma
Stage IV Bladder Cancer
Stage IV Breast Cancer
Stage IV Lymphoepithelioma of the Nasopharynx
Stage IV Melanoma
Stage IV Neuroendocrine Carcinoma of the Skin
Stage IV Non-small Cell Lung Cancer
Stage IV Pancreatic Cancer
Stage IV Prostate Cancer
Stage IV Renal Cell Cancer
Stage IV Squamous Cell Carcinoma of the Hypopharynx
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity
Stage IVA Basal Cell Carcinoma of the Lip
Stage IVA Colon Cancer
Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage IVA Follicular Thyroid Cancer
Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage IVA Lymphoepithelioma of the Oropharynx
Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity
Stage IVA Papillary Thyroid Cancer
Stage IVA Rectal Cancer
Stage IVA Salivary Gland Cancer
Stage IVA Squamous Cell Carcinoma of the Larynx
Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVA Verrucous Carcinoma of the Larynx
Stage IVA Verrucous Carcinoma of the Oral Cavity
Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity
Stage IVB Basal Cell Carcinoma of the Lip
Stage IVB Colon Cancer
Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage IVB Follicular Thyroid Cancer
Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage IVB Lymphoepithelioma of the Oropharynx
Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity
Stage IVB Papillary Thyroid Cancer
Stage IVB Rectal Cancer
Stage IVB Salivary Gland Cancer
Stage IVB Squamous Cell Carcinoma of the Larynx
Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVB Verrucous Carcinoma of the Larynx
Stage IVB Verrucous Carcinoma of the Oral Cavity
Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity
Stage IVC Basal Cell Carcinoma of the Lip
Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
Stage IVC Follicular Thyroid Cancer
Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
Stage IVC Lymphoepithelioma of the Oropharynx
Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity
Stage IVC Papillary Thyroid Cancer
Stage IVC Salivary Gland Cancer
Stage IVC Squamous Cell Carcinoma of the Larynx
Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IVC Squamous Cell Carcinoma of the Oropharynx
Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
Stage IVC Verrucous Carcinoma of the Larynx
Stage IVC Verrucous Carcinoma of the Oral Cavity
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Thyroid Gland Medullary Carcinoma
Tongue Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Waldenström Macroglobulinemia
Drug: romidepsin
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Drug Information available for: Romidepsin
Genetic and Rare Diseases Information Center resources: Pancreatic Cancer Malignant Mesenchymal Tumor Soft Tissue Sarcoma Anaplastic Astrocytoma Pancreatic Islet Cell Tumors Insulinoma Somatostatinoma Glucagonoma Lymphoma, Small Cleaved-cell, Diffuse Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Acute Lymphoblastic Leukemia Follicular Lymphoma Lymphoma, Large-cell Leukemia, T-cell, Chronic Mycosis Fungoides Sezary Syndrome Cutaneous T-cell Lymphoma Lymphoblastic Lymphoma B-cell Lymphomas Burkitt Lymphoma Lymphoma, Large-cell, Immunoblastic Plasmablastic Lymphoma Hodgkin Lymphoma Mantle Cell Lymphoma Waldenstrom Macroglobulinemia Anaplastic Large Cell Lymphoma Small Non-cleaved Cell Lymphoma Lymphomatoid Granulomatosis Peripheral T-cell Lymphoma Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Large Granular Lymphocyte Leukemia Lymphosarcoma Kidney Cancer Renal Cancer Glioblastoma Gliosarcoma Metastatic Squamous Neck Cancer With Occult Primary Adenoid Cystic Carcinoma Brain Tumor, Adult Breast Cancer, Male Mucoepidermoid Carcinoma Esthesioneuroblastoma Nasopharyngeal Carcinoma Midline Lethal Granuloma Laryngeal Cancer Hypopharyngeal Cancer Tongue Cancer Glioma Oligodendroglioma Anaplastic Oligodendroglioma Central Nervous System Lymphoma, Primary Hairy Cell Leukemia Ependymoma Carcinoid Tumor Pheochromocytoma Merkel Cell Carcinoma Paragangliomas 1 Thyroid Cancer, Medullary Anaplastic Ependymoma Embryonal Tumor With Multilayered Rosettes Thyroid Cancer, Anaplastic Papillary Thyroid Carcinoma Thyroid Cancer, Follicular Zollinger-Ellison Syndrome Glucagonoma Syndrome Rectal Neoplasm Carcinoid Syndrome Neuroepithelioma Oral Cancer Neuroblastoma
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD 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 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    PK 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.


Secondary Outcome Measures:
  • Child-Pugh classification of hepatic dysfunction [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Association of antitumor activity and romidepsin treatment will be documented.


Estimated Enrollment: 132
Study Start Date: June 2012
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: romidepsin
Given IV
Other Names:
  • FK228
  • FR901228
  • Istodax
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed (at original diagnosis or subsequent recurrence or progression) lymphoma, chronic lymphocytic lymphoma (CLL) or solid tumor; patients with lymphoma or CLL must have radiologically or clinically evaluable disease, and be refractory to standard therapy as defined by relapse within 6 months of last treatment (see note below); patients with solid tumors must have radiologically or clinically evaluable disease that is metastatic, unresectable, progressive, or recurrent, and for which standard curative measures do not exist or are no longer effective

    • Patients with a liver mass, raised alpha-fetoprotein level (>= 500 ng/mL) and positive serology for hepatitis, consistent with a diagnosis of hepatocellular carcinoma will be eligible without the need for pathologic confirmation of the diagnosis
    • Patients with prostate cancer, renal cell cancer, neuroendocrine tumors, lung cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer are excluded in the normal and mild cohorts due to a lack of efficacy in these tumor types in phase 2 studies; patients with breast, pancreatic, bladder, head and neck cancers, as well as melanoma and other malignancies are eligible
    • Note: patients with prostate cancer, renal cell cancer, lung cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer are allowed to enroll in the moderate and severe cohorts provided the patients:

      • Sign a separate consent form which outlines the lack of efficacy observed in prior studies
      • Are consented to the study by a protocol-specified designee who is not their longitudinal oncologist; patients with neuroendocrine tumors are still excluded from the moderate and severe cohorts
    • Note: as romidepsin is approved for patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) or cutaneous T cell lymphoma (CTCL), these patients would be eligible WITHOUT the requirement of having 'relapsed within 6 months of last treatment'
  • Life expectancy of > 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Hemoglobin >= 9 g/dL (transfusions and/or erythropoietin are permitted)
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L (or platelet count >= 30 × 10^9 cells/L in patients with lymphoma or CLL if bone marrow disease involvement is documented)
  • Creatinine =< twice upper limit institutional normal
  • Patients with abnormal liver function will be eligible and will be grouped according to the criteria below

    • Group A (normal hepatic function)

      • Bilirubin =< upper limit of normal (ULN) and aspartate aminotransferase (AST) =< ULN
    • Group B (mild hepatic dysfunction)

      • B1: bilirubin =< ULN and AST > ULN
      • B2: bilirubin > ULN but =< 1.5 x ULN and any AST
    • Group C (moderate hepatic dysfunction)

      • Bilirubin > 1.5 x ULN to =< 3 x ULN and any AST
    • Group D (severe hepatic dysfunction)

      • Bilirubin > 3 x ULN and up to investigators discretion and any AST
    • Patients with active hemolysis should be excluded; no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes; registration laboratory investigations will be used to assign a patient to a hepatic function group; liver function tests should be repeated within 24 hours prior to starting initial therapy and may result in the patients' group assignment being altered if different to registration test results
  • Patients with brain metastases who require corticosteroids or non-enzyme inducing anticonvulsants must be on a stable dose of corticosteroids and seizure free for 1 month prior to enrollment; patients with known brain metastases should have completed brain irradiation (whole brain or gamma knife) more than 4 weeks before starting the protocol; patients on enzyme inducing anticonvulsants are not eligible; note that patients should have had their steroids tapered to low dose (i.e. < 1.5 mg of dexamethasone/day) due to the potential for higher dexamethasone doses to induce cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
  • Patients with biliary obstruction for which a stent has been placed are eligible, provided the shunt has been in place for at least 10 days prior to the first dose of romidepsin and the liver function has stabilized; two measurements at least 2 days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function; there should be no evidence of biliary sepsis
  • Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or PK of romidepsin will be determined following review of their case by the site principal investigator

    • Patients treated with any of the medications prohibited must discontinue their use at least 7 days prior to the first dose of romidepsin; certain other agents that interact with the CYP3A4 system may be used with caution
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; note: since romidepsin binds to the estrogen receptor, the effectiveness of estrogen containing contraceptives may be reduced
  • Human immunodeficiency virus (HIV)-positive patients who are not receiving: agents with the potential for PK interactions with romidepsin or hepatotoxic antiretrovirals (nucleoside reverse-transcriptase inhibitors [NRTIs]: abacavir, didanosine, emtricitabine, lamivudine, stavudine, and zidovudine), dual protease inhibitor (PI)-based regimens except low-dose boosting with ritonavir, atazanavir, indinavir, maraviroc, and nevirapine may be eligible; additionally, the HIV-positive patients should have a cluster of differentiation (CD)4 count > 250/mm^3; if the specific cause of hepatic dysfunction is unknown, the patient should be worked up for other viral causes of hepatitis and their eligibility determined after consultation with the principal investigator
  • Patients who have received prior romidepsin use are eligible
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had (prior to entering the study): major surgery is not permitted within 4 weeks of romidepsin administration; anti-cancer therapy including chemotherapy, radiotherapy, hormonal (with the exception of hormones for thyroid conditions), and other investigational agents will not be allowed within 14 days or five (5) half-lives (whichever is longer) prior to the first dose of romidepsin (6 weeks for nitrosoureas or mitomycin C); additionally, participants must have recovered to less than grade 2 clinically significant adverse effect(s)/toxicity(ies) of the previous therapy, with the exception of alopecia, unless approved by the principal investigator; biologics or immunotherapy will not be allowed within 28 days prior to, or during, romidepsin administration
  • Patients with prostate cancer, renal cell cancer, neuroendocrine tumors, lung cancer, colorectal cancers, soft tissue sarcomas, glioma, and thyroid cancer are excluded in the normal and mild cohorts due to a lack of efficacy in these tumor types in phase 2 studies; patients with prostate cancer, renal cell cancer, lung cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer are allowed to enroll in the moderate and severe cohorts only; patients with neuroendocrine tumors are still excluded from the moderate and severe cohorts
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to romidepsin, including cyclic tetrapeptide compounds
  • Concurrent medications associated with a risk of corrected QT interval (QTc) prolongation and/or Torsades de Pointes are not allowed within 2 weeks of initiation of study treatment; those medications as reported but lacking substantial evidence for causing QTc prolongation and Torsades de Pointes will be allowed, although if an alternative medication can be substituted, that would be preferable
  • Thiazolidinedione agents such as rosiglitazone and pioglitazone are not permitted
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with current evidence of significant cardiovascular disease (New York Heart Association class III or IV cardiac disease), symptomatic congestive heart failure, dilated/hypertrophic or restrictive cardiomyopathy, myocardial infarction (within the past 6 months), unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medications for rate control for atrial fibrillation is allowed such as calcium channel blockers and beta-blockers, if stable medication for at least last month prior to initiation of romidepsin treatment and medication not listed as causing Torsades de Pointes), or evidence of acute ischemia on electrocardiogram (ECG); marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 450 msec*; long QT syndrome; the required use of concomitant medication that may cause Torsades de Pointes or may cause a significant prolongation of the QTc

    • Note: due to difficulties assessing QTc in patients with heart block, they may be eligible if deemed safe by a cardiologist
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with this drug
  • Warfarin is not permitted
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01638533

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Vincent Chung    626-471-9200    vchung@coh.org   
Principal Investigator: Vincent Chung         
University of California at Davis Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Karen L. Kelly    916-734-3735    karen.kelly@ucdmc.ucdavis.edu   
Principal Investigator: Karen L. Kelly         
City of Hope South Pasadena Recruiting
South Pasadena, California, United States, 91030
Contact: Stephen C. Koehler    626-396-2900    skoehler@cohmg.com   
Principal Investigator: Stephen C. Koehler         
United States, Maryland
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Roisin M. Connolly    410-614-9217    rconnol2@jhmi.edu   
Principal Investigator: Roisin M. Connolly         
National Cancer Institute Developmental Therapeutics Clinic Recruiting
Bethesda, Maryland, United States, 20892
Contact: Roisin M. Connolly    410-614-9217    rconnol2@jhmi.edu   
Principal Investigator: Roisin M. Connolly         
United States, Michigan
Wayne State University/Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Ulka N. Vaishampayan    313-576-8718    vaishamu@karmanos.org   
Principal Investigator: Ulka N. Vaishampayan         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Paul Haluska    507-284-2511    haluska.paul@mayo.edu   
Principal Investigator: Paul Haluska         
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Afshin Dowlati    216-844-1228    axd44@case.edu   
Principal Investigator: Afshin Dowlati         
United States, Pennsylvania
Penn State Milton S Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Chandra P. Belani    717-531-1078    cbelani@psu.edu   
Principal Investigator: Chandra P. Belani         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Roisin M. Connolly    410-614-9217    rconnol2@jhmi.edu   
Principal Investigator: Roisin M. Connolly         
Canada, Ontario
University Health Network-Princess Margaret Hospital Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Lillian L. Siu    416-946-2911    lillian.siu@uhn.ca   
Principal Investigator: Lillian L. Siu         
Sponsors and Collaborators
Investigators
Principal Investigator: Roisin Connolly Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01638533     History of Changes
Other Study ID Numbers: NCI-2012-01040, NCI-2012-01040, NCI-2013-01545, CDR0000737061, J11105, 9008, UM1CA186691, UM1CA186717, U01CA069912, UM1CA186686, UM1CA186690, U01CA062505, UM1CA186644, P30CA006973, U01CA070095, U01CA132123
Study First Received: July 9, 2012
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Salivary Gland Neoplasms
Sarcoma
Pancreatic Neoplasms
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Carcinoma, Non-Small-Cell Lung
Neoplasms
Carcinoma, Squamous Cell
Melanoma
Lymphoma, Follicular
Lung Neoplasms
Prostatic Neoplasms
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Hodgkin Disease
Lymphoma, B-Cell, Marginal Zone
Mycosis Fungoides
Oropharyngeal Neoplasms
Carcinoma, Renal Cell
Carcinoma, Verrucous
Lymphoma, T-Cell
Sezary Syndrome
Thyroid Neoplasms
Lymphoma, T-Cell, Cutaneous
Lymphoma, B-Cell
Thyroid Diseases
Burkitt Lymphoma
Lymphoma, Large-Cell, Immunoblastic

ClinicalTrials.gov processed this record on September 22, 2014