AzTrials
AzTrials

Pancreas CancerPhase 1NCT03760614

A Study of Entinostat and FOLFOX in Subjects With Pancreatic Adenocarcinoma

A Phase 1 study testing Entinostat and FOLFOX regimen in people with Pancreas Cancer, run by Abramson Cancer Center at Penn Medicine.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

The main purpose of this study is to find the best dose of entinostat when given in combination with FOLFOX for pancreatic cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreas Cancer
What is being tested?
Entinostat and FOLFOX regimen
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jan 2021to Nov 2022
Phase
Phase 1
Are there results?
None posted in the registry

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

  • 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
Show all 17Show fewer
  • 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:
  • Hematology: ANC ≥1.5 x 109/L (≥1500 cells / mm3); Platelet count ≥ 150 x 109/L (≥150,000 cells/mm3); Hb ≥ 9g/dl (≥9 mg/L)
  • Coagulation: INR and aPTT ≤1.5 x ULN.
  • Hepatic function: bilirubin ≤1.5 x ULN; AST / ALT ≤ 2.5 x ULN (or ≤ 5 x ULN in the presence of liver metastasis)
  • Renal: Creatinine < 1.5x ULN or calculated creatinine clearance ≥ 50ml/min calculated as per local institution standards.
  • 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:
  • ≥45 years of age and has not had menses for >2 years
  • Amenorrhoeic 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 subject 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
  • Tumor sites amenable to repeated biopsies.
  • Willingness to undergo paired tumor biopsies during the trial.

Who cannot join

  • 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.
Show all 15Show fewer
  • 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.

About this study

Official title: A Phase Ib Study of Entinostat and FOLFOX in Subjects With Pancreatic Adenocarcinoma

The main purpose of this study is to find the best dose of entinostat when given in combination with FOLFOX for pancreatic cancer.

Conditions
Pancreas Cancer
Being tested
Entinostat, FOLFOX regimen
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EntinostatDrug

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

  • FOLFOX regimenDrug

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

Study groups in NCT03760614
Study groupRoleWhat they receive
Entinostat + FOLFOXExperimentalFOLFOX 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 enrollment and observed toxicities. Dosing will begin at 3mg.
Receives: Drug: Entinostat; Drug: FOLFOX regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicity (DLT)

    Dose limiting toxicity (DLT)

    Measured: During the first 28 days of treatment

Secondary outcomes (3)

  1. Incidence, nature and severity of adverse events (AE)

    Incidence, nature and severity of adverse events (AE)

    Measured: 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)

  2. Progress free survival (PFS)

    Progress free survival (PFS)

    Measured: From study entry until disease progress or death from any cause, whichever occurs first (assessed at 6 months)

  3. Overall response rate (ORR)

    Overall response rate (ORR) as defined as proportion of patients with complete response (CR) or partial response (PR)

    Measured: Through study completion, estimated 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Nov 2018
  2. Study startJan 2021 (estimated)
  3. Primary completionJul 2022 (estimated)
  4. Study completionNov 2022 (estimated)

Why it stopped: Lack of Funding

Resources

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
Not applicable
Intervention model
Sequential
Model description
This will be a modified 3+3 dose-escalation design with a primary endpoint of dose-limiting toxicity. All cohorts will receive the same dose of FOLFOX, once every 2 weeks. All cohorts will receive entinostat on days 1,8, 15, and 22 of 28 day cycles. Cohorts will vary in their dose of entinostat as follows: * Cohort 0: 2mg * Cohort 1: 3mg * Cohort 2: 4mg * Cohort 3: 5mg Dosing will start with cohort 1. If no dose limiting toxicities (DLTs) are observed, the dose will be escalated directly to cohort 3. If any DLTs are experienced in cohort 1, three additional subjects will be enrolled in cohort 1. If no DLTs are experience by the additional subjects, the dose will be escalated to cohort 2. If a DLT occurs in two subjects in any dose cohort, dose escalation will be halted, and the next three subjects will be enrolled at the next lower dose cohort.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03760614
Sponsor's protocol ID
UPCC 19218
Status last verified
Jan 2021
First submitted
26 Nov 2018
Last updated
15 Jan 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Tost J, Ak-Aksoy S, Campa D, Corradi C, Farinella R, Ibanez-Costa A, Dubrot J, Earl J, Melian EB, Kataki A, Kolnikova G, Madjarov G, Chaushevska M, Strnadel J, Tanic M, Tomas M, Dubovan P, Urbanova M, Buocikova V, Smolkova B. Leveraging epigenetic alterations in pancreatic ductal adenocarcinoma for clinical applications. Semin Cancer Biol. 2025 Feb;109:101-124. doi: 10.1016/j.semcancer.2025.01.003. Epub 2025 Jan 23.

    PubMed 39863139

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Entinostat and FOLFOX regimen in people with Pancreas Cancer, run by Abramson Cancer Center at Penn Medicine.

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 17 inclusion and 15 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: withdrawn, as of the sponsor's last update on 15 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Dose limiting toxicity (DLT) (time frame: During the first 28 days of treatment). 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 NCT03760614, 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 15 Jan 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in