A Study Of Entinostat And FOLFOX In Subjects With Pancreatic Adenocarcinoma

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2018-11-26	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2021-01-13
First Submitted that Met QC Criteria 2018-11-29	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2021-01-15
First Posted (ACTUAL) 2018-11-30	Results First Posted N/A	Last Verified 2021-01

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Entinostat + FOLFOX FOLFOX will be administered intravenously (IV), into a vein, using a port-a-cath every 2 weeks. Entinostat will be administered orally on days 1, 8, 15 and 22 of each 28-day cycle. Entinostat dose will vary between 2mg and 5mg depending on time of enrollm	DRUG: Entinostat Entinostat will be administered orally on days 1, 8, 15 and 22 of each 28-day cycle. DRUG: FOLFOX regimen FOLFOX will be administered intravenously (IV), into a vein, using a port-a-cath every 2 weeks.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Entinostat + FOLFOX

FOLFOX will be administered intravenously (IV), into a vein, using a port-a-cath every 2 weeks. Entinostat will be administered orally on days 1, 8, 15 and 22 of each 28-day cycle. Entinostat dose will vary between 2mg and 5mg depending on time of enrollm

DRUG: Entinostat

Entinostat will be administered orally on days 1, 8, 15 and 22 of each 28-day cycle.

DRUG: FOLFOX regimen

FOLFOX will be administered intravenously (IV), into a vein, using a port-a-cath every 2 weeks.

Primary Outcome Measures	Measure Description	Time Frame
Dose limiting toxicity (DLT)	Dose limiting toxicity (DLT)	During the first 28 days of treatment

Secondary Outcome Measures	Measure Description	Time Frame
Incidence, nature and severity of adverse events (AE)	Incidence, nature and severity of adverse events (AE)	From time of enrollment until completion of the Safety Visit 30 days (+/- 7) days after last dose of entinostat (treatment with entinostat may continue until disease progression, death, unacceptable toxicites or withdrawal, estimated time 6 months)
Progress free survival (PFS)	Progress free survival (PFS)	From study entry until disease progress or death from any cause, whichever occurs first (assessed at 6 months)
Overall response rate (ORR)	Overall response rate (ORR) as defined as proportion of patients with complete response (CR) or partial response (PR)	Through study completion, estimated 1 year

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Willing and able to provide written informed consent.
Ability to comply with the protocol.
Aged ≥ 18 years.
Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma that has progressed after first-line gemcitabine+nab-paclitaxel-based chemotherapy.
ECOG PS of 0 or 1
At least one lesion that can be measured accurately at baseline as ≥10mm in the longest diameter (except lymph nodes which must have a short axis ≥15mm) with CT/MRI and which is suitable for repeated measurements per RECIST v1.1
Adequate hematological and end-organ function, as per the local institutions reference ranges, within 72 hrs prior to day 1 of cycle 1 of treatment defined by the following:

Negative serum or urine pregnancy test within 14 days of day 1 cycle 1 for female subjects of childbearing potential. Female subjects of childbearing potential as well as male subjects must agree to use effective contraception during the study and for 120 days after the last of entinostat. Non-childbearing potential is defined as:

Tumor sites amenable to repeated biopsies.
Willingness to undergo paired tumor biopsies during the trial.

Subjects with known or suspected brain metastasis
Significant cardiovascular disease such as New York Heart Associate Class III/IV, cardiac failure, myocardial infarction within 6 months prior to enrolment, unstable arrhythmia, or evidence of ischemia on ECG.
Baseline QTc exceeding 450msec (470msec for females) and / or subjects receiving class 1A or class III anti-arrhythmic agents.
Known HIV or active hepatitis A, B or C infection (with positive viral PCR).
Malignancies other than pancreatic cancer ≤5 years prior to Entinostat and FOLFOX cycle 1 day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcomes (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of PSA relapse or incidental prostate cancer (Gleason score ≤3 +4 and PSA <10ng/L undergoing active surveillance and treatment naïve).
Severe infections ≤ 4 weeks prior to enrolment in the study as well as active, uncontrolled bacterial, viral or fungal infections requiring systemic treatment.
Major surgical procedure ≤ 2 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
Treatment with chemotherapy or other investigational agents within 28 days (or at least 5 x the half-life of the drug) prior to day 1 cycle 1 of Entinostat and FOLFOX (6 weeks for nitrosoureas or Mitomycin C).
Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational medicinal product (IMP) within ≤ 5 x the half-life of the IMP prior to day 1 cycle 1 of Entinostat and FOLFOX.
Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of Entinostat or FOLFOX, may affect the interpretation of the results, render the subject at high risk from treatment complications or interferes with obtaining informed consent.
Female subjects who are pregnant or nursing.
Pre-existing neuropathy > CTCAE Grade 2
Previous treatment with platinum agents
Allergy to benzamide or inactive components of entinostat
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.

Collaborators and Investigators

Publications

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Resources

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Caregivers

Clinical Trial Record