Vorinostat Plus Hydroxychloroquine Versus Regorafenib in Colorectal Cancer

NCT02316340 | Completed Phase 2 Results DMC

• 1 other identifier: CTMS 14-2015
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy Based on Progression Free Survival of Vorinostat and Hydroxychloroquine Compared to Regorafenib

  CT Scan performed every 8 weeks to monitor progression for one year.

  Baseline to 12 months

Secondary Outcomes (1)

• Median Overall Survival (mOS)

  Baseline up to 22 months

Study Arms (2)

Study Arm - VOR with HCQ

EXPERIMENTAL

Patients will be given vorinostat 400 mg daily and hydroxychloroquine 600 mg daily in 4 week cycles.

Drug: Vorinostat; Drug: Hydroxychloroquine

Control Arm - Regorafenib

ACTIVE COMPARATOR

Patients will be given oral RGF 160 mg daily for 3 weeks in 4 week cycles.

Drug: Regorafenib

Interventions

Vorinostat DRUG

400mg by mouth daily

Also known as: Zolinza, SAHA, VOR

Study Arm - VOR with HCQ

Hydroxychloroquine DRUG

600mg by mouth daily

Also known as: HCQ, plaquenil

Study Arm - VOR with HCQ

Regorafenib DRUG

160 mg by mouth daily

Also known as: Stivarga, RGF

Control Arm - Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

Cancer Therapy and Research Center University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Arora SP, Tenner L, Sarantopoulos J, Morris J, Liu Q, Mendez JA, Curiel T, Michalek J, Mahalingam D. Modulation of autophagy: a Phase II study of vorinostat plus hydroxychloroquine versus regorafenib in chemotherapy-refractory metastatic colorectal cancer (mCRC). Br J Cancer. 2022 Oct;127(6):1153-1161. doi: 10.1038/s41416-022-01892-6. Epub 2022 Jun 23.

  PMID: 35739299 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Vorinostat; Hydroxychloroquine; regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Sukeshi Arora
• Organization: UT Health San Antonio

ARORAS@UTHSCSA.EDU

2104502872

Study Officials

• Sukeshi Patel Arora, MD

  University of Texas Health Science Center at the Cancer Therapy and Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 9, 2014
• First Posted: December 12, 2014
• Study Start: February 11, 2015
• Primary Completion: March 7, 2018
• Study Completion: April 16, 2018
• Last Updated: January 5, 2024
• Results First Posted: January 5, 2024

Record last verified: 2024-01

Locations

US (1)