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Vorinostat Plus Hydroxychloroquine Versus Regorafenib in Colorectal Cancer

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: NCT02316340
Recruitment Status : Active, not recruiting
First Posted : December 12, 2014
Last Update Posted : October 25, 2019
Sponsor:
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio

Tracking Information
First Submitted Date  ICMJE December 9, 2014
First Posted Date  ICMJE December 12, 2014
Last Update Posted Date October 25, 2019
Study Start Date  ICMJE February 2015
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2014)
Efficacy based on progression free survival of vorinostat and hydroxychloroquine compared to Regorafenib [ Time Frame: Every 8 weeks ]
CT Scan
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02316340 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vorinostat Plus Hydroxychloroquine Versus Regorafenib in Colorectal Cancer
Official Title  ICMJE Modulation of Autophagy: A Clinical Study of Vorinostat Plus Hydroxychloroquine Versus Regorafenib in Refractory Metastatic Colorectal Cancer (mCRC) Patients (CTMS# 14-2015)
Brief Summary This will be a randomized phase II clinical trial of patients with histologic documentation of metastatic colorectal cancer, who have received local and currently approved standard therapies, excluding RGF.
Detailed Description The investigators will give VOR 400 mg PO daily and HCQ 600 mg PO daily in 4-week cycles. Patients will require imaging up to 6 weeks prior to enrollment and will be assessed for measureable evidence of mCRC. This will be a randomized, controlled phase II clinical trial of patients with histological documentation of metastatic colorectal cancer, who have received locally and currently approved standard therapies, excluding RGF. Patients will be randomized 1:1 to RGF or VOR/HCQ (see schema below). Also, crossover is optional after first progression on the initial therapy, and based on physician discretion and in the best interest of the patient. If crossover is not done, then the patient will be off study and can go on to receive other treatments.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Drug: Vorinostat
    400mg by mouth daily
    Other Names:
    • Zolinza
    • SAHA
    • VOR
  • Drug: Hydroxychloroquine
    600mg by mouth daily
    Other Names:
    • HCQ
    • plaquenil
  • Drug: Regorafenib
    160 mg by mouth daily
    Other Names:
    • Stivarga
    • RGF
Study Arms  ICMJE
  • Experimental: Study Arm - VOR with HCQ
    Patients will be given vorinostat 400 mg daily and hydroxychloroquine 600 mg daily in 4 week cycles.
    Interventions:
    • Drug: Vorinostat
    • Drug: Hydroxychloroquine
  • Active Comparator: Control Arm - Regorafenib
    Patients will be given oral RGF 160 mg daily for 3 weeks in 4 week cycles.
    Intervention: Drug: Regorafenib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 11, 2014)
76
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histological documentation of metastatic colorectal cancer (mCRC)
  • ECOG performance status of 0-2
  • Radiographical documentation of metastatic disease with imaging up to 6 weeks prior to enrollment
  • Patients with mCRC must have been previously treated with irinotecan and/or oxaliplatin and/or VEGF/EGFR therapy or intolerant to these agents
  • Documentation of K-Ras mutational status
  • Adequate hematologic, renal and liver function (i.e. absolute neutrophil count > 1000/mm3, platelets > 75,000/mm3); creatinine < 2 times the upper limits of normal (ULN) total bilirubin < 1.5 mg/dl, ALT and AST< 3 times above the ULN, ALT and AST can be < 5 times ULN if patients have hepatic involvement.
  • Able to provide written informed consent
  • Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test within 72 hours prior to receiving the investigational product
  • Tumor blocks available from previous surgery/biopsy, or if not available, patients willing to have biopsy

Exclusion Criteria:

  • Patients receiving prior therapy with RGF, VOR, and/or HCQ
  • Patients with uncontrolled brain metastases. Patients with brain metastases must be asymptomatic and off corticosteroids for at least one week
  • Due to risk of disease exacerbation, patients with porphyria are not eligible
  • Due to risk of disease exacerbation, patients with psoriasis are ineligible unless the disease is well controlled, and they are under the care of a specialist for the disorder who agrees to monitor the patient for exacerbations
  • Patients with previously documented macular degeneration or diabetic retinopathy
  • Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. For targeted therapies, patients will need to clear for 5 half-lives
  • Patients may not be receiving any other investigational agents
  • Patients should not have taken valproic acid or another histone deacetylase inhibitor for at least 2 weeks prior to enrollment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to VOR or HCQ
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Major surgery or significant traumatic injury occurring within 21 days prior to treatment
  • QTc > 500 ms at baseline (average of 3 determinations at 10 minutes interval)
  • Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease. Patients with NG-tube, J-tube, or G-tube will not be allowed to participate
  • Pregnant women are excluded from this study because vorinostat has the potential for teratogenic or abortifacient effects. For this reason, women of childbearing potential and men must also agree to use adequate contraception (hormonal or barrier method of birth control) 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. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued
  • Informed Consent - No study specific procedures will be performed without a written and signed informed consent document. Patients who do not demonstrate the ability to understand or the willingness to sign the written informed consent document will be excluded from study entry
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02316340
Other Study ID Numbers  ICMJE CTMS 14-2015
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The University of Texas Health Science Center at San Antonio
Study Sponsor  ICMJE The University of Texas Health Science Center at San Antonio
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sukeshi Patel Arora, MD University of Texas Health Science Center at the Cancer Therapy and Research Center
PRS Account The University of Texas Health Science Center at San Antonio
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP