Colorectal CancerPhase 1NCT03215264
To Determine the Safety of Regorafenib, Hydroxychloroquine, and Entinostat Metastatic Colorectal Cancer
A Phase 1 study testing hydroxychloroquine, entinostat and regorafenib in people with Colorectal Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
The main purpose of this study is to find the best dose of hydroxychloroquine (HCQ) when given in combination with regorafenib and entinostat. 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?
- hydroxychloroquine, entinostat and regorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Oct 2017to 1 Jun 2020
- Phase
- Phase 1
- 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
- Histologic or cytologic confirmation of metastatic colorectal cancer
- Measurable disease based on modified RECIST 1.1 criteria
- Patients should have received adequate therapy with prior 5-fluorouracil, oxaliplatin, and irinotecan, unless contra-indicated, not tolerated or declined.
- No prior therapy with regorafenib or other anti-angiogenic tyrosine kinase inhibitor
- No prior or current therapy with an HDAC inhibitor
- Age 18 years or older
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- ECOG performance status of 0 or 1
- If a female of childbearing potential, has a negative serum blood pregnancy test during screening and a negative urine pregnancy test within 3 days prior to receiving the first dose of study drug. If the screening serum test is done within 3 days prior to receiving the first dose of study drug, a urine test is not required. If a patient is of childbearing potential the patient must agree to use effective contraception (see Appendix C for acceptable methods) during the study and for 120 days after the last dose of study drug. Non-childbearing potential is defined as (by other than medical reasons):
- ≥45 years of age and has not had menses for >2 years
- Amenorrheic for <2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation
- Post hysterectomy, oophorectomy or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 120 days after the last dose of study drug
- If male, agrees to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug
- Life expectancy of greater than 3 months
- Patients must have the ability to understand and the willingness to sign a written informed consent document.
- Adequate bone-marrow, liver, and renal function as assessed by the following laboratory requirements within 4 weeks of starting treatment
- Absolute neutrophil count >1,500 per uL
- Hemoglobin > 9 g/dL
- Platelets >100,000 per uL
- Creatinine < 1.5 x ULN OR Creatinine clearance (CrCl) > 60 by Cockcroft-Gault Equation if Creatinine >1.5
- AST and ALT < 2.5 x ULN (< 5 x ULN if documented liver metastases)
- Total bilirubin <1.5 ULN OR direct bilirubin < ULN if total bilirubin > 1.5 x ULN
- INR < 2.0
- Experienced resolution of toxic effect(s) of the most recent prior anti-cancer therapy to Grade <1 (except alopecia or neuropathy). If patient underwent major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
Who cannot join
- History or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:
- Myocardial infarction or arterial thromboembolic events within 6 months prior to screening or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc interval > 470 msec.
- Uncontrolled hypertension or diabetes mellitus.
- Another known malignancy that is progressing or requires active treatment.
- Any prior history of other cancer within the prior 5 years with the exception of adequately treated basal cell carcinoma or cervical intraepithelial neoplasia [CIN]/cervical carcinoma in situ or melanoma in situ).
- Active infection requiring systemic therapy
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- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption.
- Allergy to benzamide, inactive components of entinostat, or any of the other administered therapies
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
- If female, is pregnant or breastfeeding.
- Known G6PD deficiency, severe psoriasis, porphyria, macular degeneration, or severe diabetic retinopathy due to greater potential HCQ toxicity
- Patients with pre-existing hypertension should be on a stable antihypertensive regimen and have a blood pressure ≤ 150/100 mmHg at the time of enrollment.
- Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event of CTCAE grade 3 or higher within 4 weeks of start of study medication
- Non-healing wound, ulcer, or bone fracture
- Patients using warfarin are excluded. Patients using other oral or parenteral anticoagulation are not excluded provided they are on a stable dose of anticoagulant but must undergo more frequent platelet count monitoring.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase I/II Trial of Regorafenib, Hydroxychloroquine, and Entinostat in Metastatic Colorectal Cancer
The main purpose of this study is to find the best dose of hydroxychloroquine (HCQ) when given in combination with regorafenib and entinostat.
Read the detailed description
This was a 3+3 phase I trial of HCQ and entinostat with regorafenib in patients with metastatic CRC. The primary objective was safety and the secondary objective was clinical efficacy. The trial was intended to be a Phase 1/2 trial, but the trial never moved forward to Phase 2.
- Conditions
- Colorectal Cancer
- Being tested
- hydroxychloroquine, entinostat, 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.
Also called Plaquenil · Quineprox
600-1200mg daily
entinostatDrug
Also called DB11841
3-5mg weekly
regorafenibDrug
Also called Stivarga
160mg daily
| Study group | Role | What they receive |
|---|---|---|
| Dose level 1 | Experimental | Regorafenib 160mg daily 1-21 of 28-day cycle , Entinostat 3mg weekly, HCQ 600mg daily. Receives: Drug: hydroxychloroquine; Drug: entinostat; Drug: regorafenib |
| Dose level 2 | Experimental | Regorafenib 160mg daily 1-21 of 28-day cycle Entinostat 5mg weekly, HCQ 600mg daily Receives: Drug: hydroxychloroquine; Drug: entinostat; Drug: regorafenib |
| Dose level 3 | Experimental | Regorafenib 160mg daily 1-21 of 28-day cycle, Entinostat 5mg weekly, HCQ 600mg BID (1200mg daily). Receives: Drug: hydroxychloroquine; Drug: entinostat; Drug: regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Hydroxychloroquine and Entinostat in Combination With Regorafenib
Participants were evaluable for toxicity if they have taken one dose of HCQ and one dose of entinostat. To be considered for evaluability in a Phase I cohort in the absence of dose-limiting toxicity, patients should have completed > 85% of HCQ doses, and at least 3 of 4 entinostat doses. The MTD will be defined as a) the dose producing DLT in 1 out of 6 patients, or b) the dose level below the dose which produced DLT in ≥ 2 out of 3 patients, or in ≥ 2 out of 6 patients. DLTs will be defined by toxicity occurring during the first 4 weeks of this study.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2017
- Study start2 Oct 2017
- Primary completion1 Jun 2020
- Study completion1 Jun 2020
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 Abramson Cancer Center at Penn MedicineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Standard 3+3 design to determine the maximum tolerated dose
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter O'Dwyer, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03215264
- Sponsor's protocol ID
- UPCC 31216
- Status last verified
- Jan 2023
- First submitted
- 10 Jul 2017
- Last updated
- 9 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Karasic TB, Brown TJ, Schneider C, Teitelbaum UR, Reiss KA, Mitchell TC, Massa RC, O'Hara MH, DiCicco L, Garcia-Marcano L, Amaravadi RK, O'Dwyer PJ. Phase I Trial of Regorafenib, Hydroxychloroquine, and Entinostat in Metastatic Colorectal Cancer. Oncologist. 2022 Sep 2;27(9):716-e689. doi: 10.1093/oncolo/oyac078.
PubMed 35552447
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Regorafenib, Hydroxychloroquine, and Entinostat in Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03215264
- Acronym / sponsor ID
- UPCC 31216
- Conditions
- Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- 2 Oct 2017 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 1 Jun 2020 (actual)
- First posted
- 12 Jul 2017 (actual)
- Results
- Posted 9 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to find the best dose of hydroxychloroquine (HCQ) when given in combination with regorafenib and entinostat.
Detailed description
This was a 3+3 phase I trial of HCQ and entinostat with regorafenib in patients with metastatic CRC. The primary objective was safety and the secondary objective was clinical efficacy. The trial was intended to be a Phase 1/2 trial, but the trial never moved forward to Phase 2.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Standard 3+3 design to determine the maximum tolerated dose
| Arm | Type | Receives |
|---|---|---|
| Dose level 1 | Experimental | Drug: hydroxychloroquine, Drug: entinostat, Drug: regorafenibRegorafenib 160mg daily 1-21 of 28-day cycle , Entinostat 3mg weekly, HCQ 600mg daily. |
| Dose level 2 | Experimental | Drug: hydroxychloroquine, Drug: entinostat, Drug: regorafenibRegorafenib 160mg daily 1-21 of 28-day cycle Entinostat 5mg weekly, HCQ 600mg daily |
| Dose level 3 | Experimental | Drug: hydroxychloroquine, Drug: entinostat, Drug: regorafenibRegorafenib 160mg daily 1-21 of 28-day cycle, Entinostat 5mg weekly, HCQ 600mg BID (1200mg daily). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Histologic or cytologic confirmation of metastatic colorectal cancer
- Measurable disease based on modified RECIST 1.1 criteria
- Patients should have received adequate therapy with prior 5-fluorouracil, oxaliplatin, and irinotecan, unless contra-indicated, not tolerated or declined.
- No prior therapy with regorafenib or other anti-angiogenic tyrosine kinase inhibitor
- No prior or current therapy with an HDAC inhibitor
Key exclusion criteria (17 listed)
- History or current evidence of any condition, therapy or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:
- Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption.
- Allergy to benzamide, inactive components of entinostat, or any of the other administered therapies
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
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 |
|---|---|---|
| hydroxychloroquineAlso: Plaquenil · Quineprox600-1200mg daily | Drug | Dose level 1, Dose level 2, Dose level 3 |
| entinostatAlso: DB118413-5mg weekly | Drug | Dose level 1, Dose level 2, Dose level 3 |
| regorafenibAlso: Stivarga160mg daily | Drug | Dose level 1, Dose level 2, Dose level 3 |
Primary outcome
Maximum Tolerated Dose (MTD) of Hydroxychloroquine and Entinostat in Combination With Regorafenib
Time frame: 18 months
Participants were evaluable for toxicity if they have taken one dose of HCQ and one dose of entinostat. To be considered for evaluability in a Phase I cohort in the absence of dose-limiting toxicity, patients should have completed > 85% of HCQ doses, and at least 3 of 4 entinostat doses. The MTD will be defined as a) the dose producing DLT in 1 out of 6 patients, or b) the dose level below the dose which produced DLT in ≥ 2 out of 3 patients, or in ≥ 2 out of 6 patients. DLTs will be defined by toxicity occurring during the first 4 weeks of this study.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35552447Karasic TB, Brown TJ, Schneider C, Teitelbaum UR, Reiss KA, Mitchell TC, Massa RC, O'Hara MH, DiCicco L, Garcia-Marcano L, Amaravadi RK, O'Dwyer PJ. Phase I Trial of Regorafenib, Hydroxychloroquine, and Entinostat in Metastatic Colorectal Cancer. Oncologist. 2022 Sep 2;27(9):716-e689. doi: 10.1093/oncolo/oyac078.
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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.
Peter O'Dwyer, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing hydroxychloroquine, entinostat and regorafenib in people with Colorectal Cancer, run by Abramson Cancer Center at Penn Medicine 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 23 inclusion and 17 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 9 Nov 2023. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 9 Nov 2023). 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?
Maximum Tolerated Dose (MTD) of Hydroxychloroquine and Entinostat in Combination With Regorafenib (time frame: 18 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 NCT03215264, 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 9 Nov 2023.