FR901228 in Treating Patients With Previously Treated Unresectable Locally Advanced or Metastatic Colorectal Cancer

Phase II Trial of Depsipeptide (NSC-630176) in Colorectal Cancer Patients Who Have Received Either One or Two Prior Chemotherapy Regimens for Metastatic or Locally Advanced, Unresectable Disease

RATIONALE: Drugs used in chemotherapy, such as FR901228, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well FR901228 works in treating patients with unresectable locally advanced or metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: romidepsin

Detailed Description

OBJECTIVES:

• Determine the confirmed response (complete and partial) in patients with previously treated unresectable locally advanced or metastatic colorectal cancer treated with FR901228 (depsipeptide).
• Determine the time to treatment failure and overall survival of patients treated with this drug.
• Determine the qualitative and quantitative toxic effects of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until disease progression and then every 3 months until 1 year after study entry and then every 6 months until 3 years after study entry.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 4-10 months.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36607
      • MBCCOP - Gulf Coast
  • Arizona
    • Phoenix, Arizona, United States, 85006-2726
      • CCOP - Western Regional, Arizona
    • Phoenix, Arizona, United States, 85012
      • Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)
    • Tucson, Arizona, United States, 85723
      • Veterans Affairs Medical Center - Tucson
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Veterans Affairs Medical Center - Little Rock
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Loma Linda, California, United States, 92357
      • Veterans Affairs Medical Center - Loma Linda (Pettis)
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Martinez, California, United States, 94553
      • Veterans Affairs Outpatient Clinic - Martinez
    • Oakland, California, United States, 94609-3305
      • CCOP - Bay Area Tumor Institute
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
    • Santa Rosa, California, United States, 95403
      • CCOP - Santa Rosa Memorial Hospital
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • MBCCOP - Howard University Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Veterans Affairs Medical Center - Tampa (Haley)
  • Georgia
    • Atlanta, Georgia, United States, 30342-1701
      • CCOP - Atlanta Regional
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • MBCCOP - Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60612
      • MBCCOP - University of Illinois at Chicago
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago Westside Hospital
    • Decatur, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Hines, Illinois, United States, 60141
      • Veterans Affairs Medical Center - Hines
    • Maywood, Illinois, United States, 60153-5500
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-7353
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67218
      • Veterans Affairs Medical Center - Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40502-2236
      • Veterans Affairs Medical Center - Lexington
    • Lexington, Kentucky, United States, 40536-0084
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Veterans Affairs Medical Center - New Orleans
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center at Tulane University Hospital and Clinic
    • Shreveport, Louisiana, United States, 71130-3932
      • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
    • Shreveport, Louisiana, United States, 71101-4295
      • Veterans Affairs Medical Center - Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Cancer Research Center at Boston Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Ann Arbor, Michigan, United States, 48109-0948
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201-1932
      • Veterans Affairs Medical Center - Detroit
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Royal Oak, Michigan, United States, 48073-6769
      • CCOP - Beaumont
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute at Providence Hospital - Southfield Campus
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39216
      • Veterans Affairs Medical Center - Jackson
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
    • Springfield, Missouri, United States, 65807
      • CCOP - Cancer Research for the Ozarks
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108-5138
      • Veterans Affairs Medical Center - Albuquerque
    • Albuquerque, New Mexico, United States, 87131
      • MBCCOP - University of New Mexico HSC
  • New York
    • New York, New York, United States, 10016
      • NYU Cancer Institute at New York University Medical Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534-9479
      • CCOP - Southeast Cancer Control Consortium
  • Ohio
    • Cincinnati, Ohio, United States, 45220-2288
      • Veterans Affairs Medical Center - Cincinnati
    • Cincinnati, Ohio, United States, 45267-0501
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195-9001
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Dayton, Ohio, United States, 45428-1002
      • Veterans Affairs Medical Center - Dayton
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97201-3098
      • Cancer Institute at Oregon Health and Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Charleston, South Carolina, United States, 29401-5799
      • Veterans Affairs Medical Center - Charleston
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Veterans Affairs Medical Center - Memphis
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee Cancer Institute at Methodist Central Hospital
  • Texas
    • Amarillo, Texas, United States, 79106
      • Harrington Cancer Center
    • Amarillo, Texas, United States, 79106
      • Veterans Affairs Medical Center - Amarillo
    • Fort Sam Houston, Texas, United States, 78234-6200
      • Brooke Army Medical Center
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030-4095
      • M.D. Anderson Cancer Center at University of Texas
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • Temple, Texas, United States, 76504
      • Veterans Affairs Medical Center - Temple
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • Veterans Affairs Medical Center - Salt Lake City
    • Salt Lake City, Utah, United States, 84112-5550
      • Huntsman Cancer Institute at University of Utah
  • Virginia
    • Norfolk, Virginia, United States, 23510-1115
      • Sentara Cancer Institute at Sentara Norfolk General Hospital
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Medical Center - Seattle
    • Seattle, Washington, United States, 98109
      • Puget Sound Oncology Consortium
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal cancer meeting 1 of the following criteria:

  • Locally advanced unresectable disease
  • Distant metastatic disease
• Measurable disease

• Previously treated with at least 1, but no more than 2, prior chemotherapy regimens for unresectable locally advanced or metastatic disease

  • May have included irinotecan or oxaliplatin
  • No more than 1 prior chemotherapy regimen (not oxaliplatin-based) for advanced or metastatic disease if previously treated with oxaliplatin-based adjuvant chemotherapy
  • No more than 1 prior chemotherapy regimen (not irinotecan-based) for advanced or metastatic disease if previously treated with irinotecan-based adjuvant chemotherapy
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ upper limit of normal (ULN)
• SGOT and SGPT ≤ 2.5 times ULN

Renal

• Creatinine ≤ ULN

Cardiovascular

• No New York Heart Association class III or IV congestive heart failure
• No myocardial infarction within the past year
• No uncontrolled dysrhythmias
• No poorly controlled angina
• No prior serious ventricular arrhythmia (e.g., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• No left ventricular hypertrophy
• QTc < 500 msec
• No other significant cardiac disease

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No prior allergic reaction attributed to compounds of similar chemical or biological composition to FR901228

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent anticancer immunotherapy

Chemotherapy

• See Disease Characteristics
• At least 28 days since prior chemotherapy and recovered
• No prior FR901228 (depsipeptide)
• No other concurrent anticancer chemotherapy

Endocrine therapy

• No concurrent anticancer hormonal therapy

Radiotherapy

• At least 28 days since prior radiotherapy and recovered
• No concurrent anticancer radiotherapy

Surgery

• At least 28 days since prior surgery and recovered

Other

• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent agent that causes QTc prolongation
• No concurrent hydrochlorothiazide
• No other concurrent investigational agents
• No other concurrent drugs that have histone deacetylase inhibitor activity (e.g., valproic acid)
• No other concurrent anticancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Robert P. Whitehead, MD, University of Texas

Publications and helpful links

General Publications

• Whitehead RP, Rankin C, Hoff PM, Gold PJ, Billingsley KG, Chapman RA, Wong L, Ward JH, Abbruzzese JL, Blanke CD. Phase II trial of romidepsin (NSC-630176) in previously treated colorectal cancer patients with advanced disease: a Southwest Oncology Group study (S0336). Invest New Drugs. 2009 Oct;27(5):469-75. doi: 10.1007/s10637-008-9190-8. Epub 2008 Oct 22.
• Whitehead RP, McCoy S, Wollner IS, et al.: Phase II trial of depsipeptide (NSC-630176) in colorectal cancer patients who have received either one or two prior chemotherapy regimens for metastatic or locally advanced, unresectable disease: a Southwest Oncology Group study. [Abstract] American Society of Clinical Oncology 2006 Gastrointestinal Cancers Symposium, 26-28 January 2006, San Francisco, California. A-255, 2006.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Study Completion (Actual): April 1, 2006

Study Registration Dates

• First Submitted: February 10, 2004
• First Submitted That Met QC Criteria: February 11, 2004
• First Posted (Estimate): February 12, 2004

Study Record Updates

• Last Update Posted (Estimate): June 24, 2013
• Last Update Submitted That Met QC Criteria: June 21, 2013
• Last Verified: November 1, 2005

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer; stage III colon cancer; stage III rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antibiotics, Antineoplastic; Romidepsin
• Other Study ID Numbers: CDR0000350199; SWOG-S0336