Colorectal CancerPhase 2NCT02316340
Vorinostat Plus Hydroxychloroquine Versus Regorafenib in Colorectal Cancer
A Phase 2 study testing Vorinostat, Hydroxychloroquine and Regorafenib in people with Colorectal Cancer, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Vorinostat, Hydroxychloroquine and Regorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Feb 2015to 16 Apr 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Cancer Therapy and Research Center University of Texas Health Science Center San Antonio
San Antonio, Texas, 78229
About this study
Official title: Modulation of Autophagy: A Clinical Study of Vorinostat Plus Hydroxychloroquine Versus Regorafenib in Refractory Metastatic Colorectal Cancer (mCRC) Patients (CTMS# 14-2015)
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.
Read the 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.
- Conditions
- Colorectal Cancer
- Being tested
- Vorinostat, Hydroxychloroquine, Regorafenib
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
Also called Zolinza, SAHA, VOR
400mg by mouth daily
Also called HCQ, plaquenil
600mg by mouth daily
RegorafenibDrug
Also called Stivarga, RGF
160 mg by mouth daily
| Study group | Role | What they receive |
|---|---|---|
| Study Arm - VOR with HCQ | Experimental | Patients will be given vorinostat 400 mg daily and hydroxychloroquine 600 mg daily in 4 week cycles. Receives: 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. Receives: Drug: Regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 12 months
Secondary outcomes (1)
Median Overall Survival (mOS)
Overall survival was measured in months from baseline
Measured: Baseline up to 22 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2014 (estimated)
- Study start11 Feb 2015
- Primary completion7 Mar 2018
- Study completion16 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sukeshi Patel, The University of Texas Health Science Center at San Antonio
- Investigators
- Sukeshi Patel Arora, MD, Principal investigator, University of Texas Health Science Center at the Cancer Therapy and Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02316340
- Sponsor's protocol ID
- CTMS 14-2015
- Status last verified
- Jan 2024
- First submitted
- 9 Dec 2014
- Last updated
- 5 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 35739299
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Autophagy: A Clinical Study of Vorinostat Plus Hydroxychloroquine Versus Regorafenib in Refractory Metastatic Colorectal Cancer (mCRC) Patients (CTMS# 14-2015)
- ClinicalTrials.gov ID
- NCT02316340
- Acronym / sponsor ID
- CTMS 14-2015
- Conditions
- Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Study start
- 11 Feb 2015 (actual)
- Primary completion
- 7 Mar 2018 (actual)
- Study completion
- 16 Apr 2018 (actual)
- First posted
- 12 Dec 2014 (estimated)
- Results
- Posted 5 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Arm - VOR with HCQ | Experimental | Drug: Vorinostat, Drug: HydroxychloroquinePatients will be given vorinostat 400 mg daily and hydroxychloroquine 600 mg daily in 4 week cycles. |
| Control Arm - Regorafenib | Active comparator | Drug: RegorafenibPatients will be given oral RGF 160 mg daily for 3 weeks in 4 week cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VorinostatAlso: Zolinza, SAHA, VOR400mg by mouth daily | Drug | Study Arm - VOR with HCQ |
| HydroxychloroquineAlso: HCQ, plaquenil600mg by mouth daily | Drug | Study Arm - VOR with HCQ |
| RegorafenibAlso: Stivarga, RGF160 mg by mouth daily | Drug | Control Arm - Regorafenib |
Primary outcome
Efficacy Based on Progression Free Survival of Vorinostat and Hydroxychloroquine Compared to Regorafenib
Time frame: Baseline to 12 months
CT Scan performed every 8 weeks to monitor progression for one year.
1 secondary outcome
Median Overall Survival (mOS)
Time frame: Baseline up to 22 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35739299Arora 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sukeshi Patel Arora, MD principal investigator
University of Texas Health Science Center at the Cancer Therapy and Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vorinostat, Hydroxychloroquine and Regorafenib in people with Colorectal Cancer, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy Based on Progression Free Survival of Vorinostat and Hydroxychloroquine Compared to Regorafenib (time frame: Baseline to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02316340, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2024.