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Romidepsin in Treating Patients With Relapsed Small Cell Lung Cancer

Primary Purpose

Recurrent Small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
romidepsin
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Either histologic or cytologic documentation of recurrent small cell lung carcinoma (SCLC) No more than 1 prior chemotherapy regimen; must have recurrent disease after treatment with a platinum agent (either cisplatin or carboplatin); prior chemotherapy must have been completed ≥90 days prior to documentation of relapse >= 4 weeks since prior radiation therapy; prior radiation therapy is allowed either in the context of curative intent combined modality treatment for limited stage disease, prophylactic cranial radiation or palliative radiation (to the chest, brain, or other sites) initially or at relapse Prior surgery is allowed provided patients have completely recovered from effects of procedure and >= 2 weeks have elapsed No prior treatment with depsipeptide No history of allergic reactions attributed to compounds of similar chemical or biologic composition to depsipeptide No current treatment with any other investigational agent or drugs known to have HDI activity (HDAC or histone deacetylase inhibitor) such as sodium valproate Patients with treated/controlled brain mets (defined as no need for further radiation and no requirements for steroids to control peri-tumoral edema) are eligible for this study; however, patients requiring treatment with enzyme inducing anti-convulsant drugs are not eligible; these include, but are not limited to, phenytoin, phenobarbital, carbamazepine, felbamate and primidone All Patients must have Measurable Disease Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension; the longest diameter of measurable lesions must be >= 20 mm with conventional techniques or >= 10 mm with spiral CT scan; lesions that are not considered measurable include the following: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Tumor lesions situated in a previously irradiated area ECOG Performance Status 0-1 No significant cardiac disease, including: Congestive heart failure that meets New York Heart Association (NYHA) class III/IV definitions, history of myocardial infarction within one year of study entry, uncontrolled dysrhythmias, or poorly controlled angina History of serious ventricular arrhythmia (VT or VF, >= 3 beats in a row), QTc >= 500 msec, or LVEF =< 40% by MUGA Evidence of left ventricular hypertrophy by echocardiographic criteria or by EKG criteria (Cornell voltage criteria): For Men: S in V3 plus R in aVL > 2.8 mV (28mm) For Women: S in V3 + R in aVL > 2.0 mV (20mm) Patients may not be co-medicated with an agent that causes QTc prolongation Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are not eligible because of possible pharmacokinetic interactions with depsipeptide No current treatment with potassium wasting diuretics (e.g., hydroclorothiazide); patients on such diuretics should be switched to a potassium sparing diuretic or another antihypertensive medication prior to registration Granulocytes >= 1,500/μl Platelets >= 100,000/μl Total Bilirubin =< 1.5 x ULN AST (SGOT) =< 2.5 x ULN Creatinine ≤1.5 x ULN OR Calculated Creatinine Clearance >= 60 ml/min Exclusion Criteria: Non-pregnant and non-nursing because of significant risk to the fetus/infant; the effects of depsipeptide on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because histone deacetylase inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to and for the entire duration of participation and for at least 6 weeks after completion of treatment

Sites / Locations

  • Ohio State University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (romidepsin)

Arm Description

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have continuing tumor response or stable disease after 6 courses receive 2 additional courses beyond best response.

Outcomes

Primary Outcome Measures

Objective response rate
95% confidence intervals will be estimated.

Secondary Outcome Measures

Overall survival
Described using Kaplan-Meier curves.
Failure-free survival
Described using Kaplan-Meier curves.
The frequency of toxicity occurrence, graded using the NCI CTCAE version 3.0
Tabulated by type and grade.

Full Information

First Posted
July 8, 2004
Last Updated
April 9, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00086827
Brief Title
Romidepsin in Treating Patients With Relapsed Small Cell Lung Cancer
Official Title
A Phase II Study of Single Agent Depsipeptide (FK228) (NSC 630176; IND 51,810) in Relapsed Small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
May 2004 (undefined)
Primary Completion Date
November 2006 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This phase II trial is studying how well FR901228 works in treating patients with recurrent small cell lung cancer. FR901228 may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the response rate of patients with histologically or cytologically proven small cell lung cancer (SCLC) treated with depsipeptide in the "sensitive" relapse setting. SECONDARY OBJECTIVES: I. To describe the overall survival and failure-free survival of patients with histologically proven recurrent SCLC treated with depsipeptide. II. To evaluate the toxicity of depsipeptide in patients with relapsed SCLC. III. To evaluate surrogate biological markers from peripheral blood mononuclear cells and buccal epithelial cells: p53 acetylation, histone acetylation, p21CIP1 expression. OUTLINE: Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have continuing tumor response or stable disease after 6 courses receive 2 additional courses beyond best response. Patients are followed every 3 months for 1 year and then every 6 months for 3 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (romidepsin)
Arm Type
Experimental
Arm Description
Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have continuing tumor response or stable disease after 6 courses receive 2 additional courses beyond best response.
Intervention Type
Drug
Intervention Name(s)
romidepsin
Other Intervention Name(s)
FK228, FR901228, Istodax
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Objective response rate
Description
95% confidence intervals will be estimated.
Time Frame
Up to 4 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
Described using Kaplan-Meier curves.
Time Frame
Between registration and death, assessed up to 4 years
Title
Failure-free survival
Description
Described using Kaplan-Meier curves.
Time Frame
The time between registration and disease progression or death, assessed up to 4 years
Title
The frequency of toxicity occurrence, graded using the NCI CTCAE version 3.0
Description
Tabulated by type and grade.
Time Frame
Up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Either histologic or cytologic documentation of recurrent small cell lung carcinoma (SCLC) No more than 1 prior chemotherapy regimen; must have recurrent disease after treatment with a platinum agent (either cisplatin or carboplatin); prior chemotherapy must have been completed ≥90 days prior to documentation of relapse >= 4 weeks since prior radiation therapy; prior radiation therapy is allowed either in the context of curative intent combined modality treatment for limited stage disease, prophylactic cranial radiation or palliative radiation (to the chest, brain, or other sites) initially or at relapse Prior surgery is allowed provided patients have completely recovered from effects of procedure and >= 2 weeks have elapsed No prior treatment with depsipeptide No history of allergic reactions attributed to compounds of similar chemical or biologic composition to depsipeptide No current treatment with any other investigational agent or drugs known to have HDI activity (HDAC or histone deacetylase inhibitor) such as sodium valproate Patients with treated/controlled brain mets (defined as no need for further radiation and no requirements for steroids to control peri-tumoral edema) are eligible for this study; however, patients requiring treatment with enzyme inducing anti-convulsant drugs are not eligible; these include, but are not limited to, phenytoin, phenobarbital, carbamazepine, felbamate and primidone All Patients must have Measurable Disease Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension; the longest diameter of measurable lesions must be >= 20 mm with conventional techniques or >= 10 mm with spiral CT scan; lesions that are not considered measurable include the following: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Tumor lesions situated in a previously irradiated area ECOG Performance Status 0-1 No significant cardiac disease, including: Congestive heart failure that meets New York Heart Association (NYHA) class III/IV definitions, history of myocardial infarction within one year of study entry, uncontrolled dysrhythmias, or poorly controlled angina History of serious ventricular arrhythmia (VT or VF, >= 3 beats in a row), QTc >= 500 msec, or LVEF =< 40% by MUGA Evidence of left ventricular hypertrophy by echocardiographic criteria or by EKG criteria (Cornell voltage criteria): For Men: S in V3 plus R in aVL > 2.8 mV (28mm) For Women: S in V3 + R in aVL > 2.0 mV (20mm) Patients may not be co-medicated with an agent that causes QTc prolongation Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are not eligible because of possible pharmacokinetic interactions with depsipeptide No current treatment with potassium wasting diuretics (e.g., hydroclorothiazide); patients on such diuretics should be switched to a potassium sparing diuretic or another antihypertensive medication prior to registration Granulocytes >= 1,500/μl Platelets >= 100,000/μl Total Bilirubin =< 1.5 x ULN AST (SGOT) =< 2.5 x ULN Creatinine ≤1.5 x ULN OR Calculated Creatinine Clearance >= 60 ml/min Exclusion Criteria: Non-pregnant and non-nursing because of significant risk to the fetus/infant; the effects of depsipeptide on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because histone deacetylase inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to and for the entire duration of participation and for at least 6 weeks after completion of treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Otterson
Organizational Affiliation
Cancer and Leukemia Group B
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

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Romidepsin in Treating Patients With Relapsed Small Cell Lung Cancer

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