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Pancreas CancerPhase 1/2SEPIONNCT04257448

Safety and Tolerance of Epigenetic and Immunomodulating Drugs Combined With Chemotherapeutics in Patients Suffering From Advanced Pancreatic Cancer

A Phase 1/2 study testing Romidepsin, Azacitidine and nab-Paclitaxel in people with Pancreas Cancer and Pancreatic Adenocarcinoma, run by GWT-TUD GmbH at 9 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

A multi-center, open-label phase I/II study to to determine the safety and tolerability of Azacitidine and/or Romidepsin in combination with nab-Paclitaxel/Gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC) (Part 1), followed by sequential immune targeting with programmed death-ligand… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Romidepsin, Azacitidine and nab-Paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
9 sitesGermany
Study dates
25 May 2020to 2 Jul 2024
Phase
Phase 1/2
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

  • Patients must have histologically confirmed PDAC
  • Patients must have metastatic disease (stage IV) and not received prior chemotherapy for stage IV disease
  • Patients must not have received the following drugs before: Azacitidine, Romidepsin, any checkpoint-inhibitor or immunomodulating agents such as Immunomodulatory imide drugs (IMiDs)
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1
  • Male or female, age ≥ 18 years
  • Body weight > 30 kg for inclusion into Part 2
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  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Patients must have normal organ and marrow function
  • Patients must be recovered from the effects of any prior surgery
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
  • All subjects must agree to refrain from donating blood while on study drug and for 90 days after discontinuation from this study treatment
  • All subjects must have a life expectancy of at least 12 weeks
  • Females of childbearing potential (FCBP) must agree to utilize two reliable forms of contraception simultaneously without interruption for at least 28 days before starting study drug, while participating in the study, and for at least 90 days after study treatment discontinuation
  • Males must agree to use a latex condom during any sexual contact with FCBP or a pregnant female, refrain from donating semen or sperm and not to father a child

Who cannot join

  • Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events from agents administered more than 4 weeks earlier
  • Patients receiving any other investigational agents.
  • Patients who have previously received Romidepsin, Azacitidine, Lenalidomide or Durvalumab or any programmed cell death-1 (PD1) or programmed cell death ligand 1 (PD-L1) inhibitor or participate currently on another clinical trial
  • Patients with untreated or uncontrolled brain metastases or leptomeningeal disease
  • Presence of other active illnesses
  • Any known cardiac abnormalities such as: congenital long QT syndrome; corrected QT interval (QTc interval) ≥ 470 milliseconds. Calculated from 3 ECGs using Fridericia's Correction
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  • Myocardial infarction within 6 months prior to cycle 1, day 1 (C1D1).
  • Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
  • Symptomatic coronary artery disease (CAD)
  • Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or known ejection fraction <40% by multiple gated acquisition scan (MUGA) or <50% by echocardiogram and/or MRI
  • A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD)
  • Concomitant use of any drug known to prolong QT interval
  • Concomitant use of strong CYP3A4 inhibitors
  • Lactating, pregnant or breast feeding
  • Patients with any other medical or psychological condition deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
  • Diagnosis of immunodeficiency or any condition that requires systemic steroid therapy or other forms of immunosuppressive therapy
  • Prior thromboembolic events
  • History of other malignancies
  • Any uncontrolled active systemic infection
  • Major surgery within 4 weeks prior to first dose of study drug
  • Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  • History of interstitial lung disease, idiopathic pulmonary fibrosis, or pulmonary hypersensitivity pneumonitis
  • Unable to swallow oral medication or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
  • Concomitant use of warfarin or other Vitamin K antagonists
  • Known allergy or hypersensitivity to any study drug or any of the study drug excipients
  • Unwilling or unable to participate in all required study evaluations and procedures. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of Durvalumab.
  • Active or prior documented autoimmune or inflammatory disorders
  • Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy
  • History of allogenic organ transplantation
  • Active infection including tuberculosis
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of Investigational medicinal product (IMP)
  • Subject is an employee of the sponsor

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Germany9 sites

  • Uniklinik Köln

    Cologne, 50937

  • Universitätsklinikum Essen

    Essen, 45147

  • Universitätsklinikum Frankfurt

    Frankfurt, 60590

  • Universitätsmedizin Göttingen

    Göttingen, 37075

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg, 20251

  • Ludwig-Maximilians-Universität München

    München, 81377

  • Klinikum Nürnberg

    Nuremberg, 90419

  • Universitätsklinikum Ulm

    Ulm, 89081

  • Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

About this study

Official title: A Multicenter, Phase I/II Study of Sequential Epigenetic and Immune Targeting in Combination With Nab-Paclitaxel/Gemcitabine in Patients With Advanced Pancreatic Ductal Adenocarcinoma.

A multi-center, open-label phase I/II study to to determine the safety and tolerability of Azacitidine and/or Romidepsin in combination with nab-Paclitaxel/Gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC) (Part 1), followed by sequential immune targeting with programmed death-ligand (PD-L)1 blockade in combination with low-dose Lenalidomide (Part 2) in patients with controlled disease after 3 cycles (Part 1).

Read the detailed description

The first part of the study will employ a standard 3 + 3 design to test safety and tolerability of histone deacetylase (HDAC) inhibition with Romidepsin (Arm A), DNA methyltransferase (DNMT) inhibition with Azacitidine (Arm B) or both agents (Arm C), in each arm in combination with nab-Paclitaxel/Gemcitabine (Part 1a). Study treatment is given until intolerable toxicity as defined in the protocol. Treatment will escalate until the recommended dose for RDE is identified.

For the expansion part (Part 1b) of the study, one of the treatment arms (Arm C over B over A) will be continued using a Simon Two-stage design to a maximum of 35 patients.

All patients from Part 1a and 1b will be treated for a total of three cycles and will then enter the second part of the study in case of disease control with still measurable disease (PR, SD).

In the second part (Part 2) of the study (consolidation therapy), all patients from Part 1 (dose escalation and expansion cohorts from experimental arms and standard arm) who have not progressed after three cycles of nab-Paclitaxel/Gemcitabine with or without additional epigenetic treatment (= at least SD by RECIST 1.1 after 3 cycles) receive sequential immune targeting with PD-L1 blockade (standard fixed dose Durvalumab 1500 mg q4w iv) in combination with low-dose Lenalidomide (10 mg d1-21 q4w po) until documented disease progression.

Medical subject headings
Pancreatic Neoplasms

What participants receive

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

  • RomidepsinDrug

    Also called Istodax

    Powder and solvent for solution for infusion; Intravenous use

  • AzacitidineDrug

    Also called Vidaza

    Powder for suspension for injection; Subcutaneous use

  • nab-PaclitaxelDrug

    Also called Abraxane

    Powder for suspension for injection; Intravenous use

  • GemcitabineDrug

    Powder for solution for infusion; Intravenous use

  • DurvalumabDrug

    Also called Imfinzi

    Concentrate for solution for infusion; Intravenous use

  • Lenalidomide capsuleDrug

    Also called Revlimid

    Hard capsule for oral use

Study groups in NCT04257448
Study groupRoleWhat they receive
Romidepsin/nab-Paclitaxel/Gemcitabine (Arm A)ExperimentalPart 1a: Romidepsin (2 mg/m² or 3.3 mg/m² or 7 mg/m²) will be administered in combination with nab-Paclitaxel (125 mg/m²)/Gemcitabine (1000 mg/m²) on Day 1, Day 8 and Day 15 (every 28 days) of each treatment cycle. Study treatment is given until intolerable toxicity or will escalate until the recommended dose for expansion for a maximum of 3 cycles.
Receives: Drug: Romidepsin; Drug: nab-Paclitaxel; Drug: Gemcitabine
Azacitidine/nab-Paclitaxel/Gemcitabine (Arm B)ExperimentalPart 1a: Azacitidine (20 mg/m² or 30 mg/m² or 40 mg/m²) will be administered on Days -7 to Day -3 of each treatment cycle. Additionally nab-Paclitaxel (125 mg/m²)/Gemcitabine (1000 mg/m²) will be given on Day 1, Day 8 and Day 15 (every 28 days) of each treatment cycle. Study treatment is given until intolerable toxicity or will escalate until the recommended dose for expansion for a maximum of 3 cycles.
Receives: Drug: Azacitidine; Drug: nab-Paclitaxel; Drug: Gemcitabine
Romidepin/Azacitidine/nab-Paclitaxel/Gemcitabine (Arm C)ExperimentalPart 1a: The intervention to be administered depends on the determined dose in Arm A and Arm B. Additionally nab-Paclitaxel (125 mg/m²)/Gemcitabine (1000 mg/m²) will be given on Day 1, Day 8 and Day 15 (every 28 days) of each treatment cycle. Study treatment is given until intolerable toxicity or will escalate until the recommended dose for expansion for a maximum of 3 cycles.
Receives: Drug: Romidepsin; Drug: Azacitidine; Drug: nab-Paclitaxel; Drug: Gemcitabine
nab-Paclitaxel/Gemcitabine (Standard Arm)Active comparatornab-Paclitaxel (125 mg/m²)/Gemcitabine (1000 mg/m²) will be administered on Day 1, Day 8 and Day 15 (every 28 days) of each treatment cycle.
Receives: Drug: nab-Paclitaxel; Drug: Gemcitabine
Arm C or B or AExperimentalIn Part 1b (expansion part) of the study, one of the treatment arms (Arm C over Arm B over Arm A) will be continued. Treatment will only be performed with the study drug that were tolerable in Part 1a (dose escalation).
Receives: Drug: Romidepsin; Drug: Azacitidine; Drug: nab-Paclitaxel; Drug: Gemcitabine
Durvalumab/LenalidomideExperimentalPart 2: All patients from Part 1 who have not progressed after three cycles receive standard fixed dose Durvalumab (1500 mg) on Day 1 of each 28-day treatment cycle by IV infusion in combination with orally administered low-dose Lenalidomide (10 mg) on Days 1 to 21 until documented disease progression. Study treatment is given for a maximum of 13 cycles.
Receives: Drug: Durvalumab; Drug: Lenalidomide capsule

What is being measured

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

  1. Safety and tolerability of Azacitidine and/or Romidepsin in combination with nab-Paclitaxel/Gemcitabine

    Dose limiting toxicities occurring during treatment cycle 1 of a respective dose level and regarded to be related to the studied drug combination. Common terminology criteria for adverse events (CTCAE) 5.0 will be used to assess toxicities.

    Measured: at Days -7, -4, 1, 8, 15, 22 at cycle 1 (each cycle is 28 days)

  2. Immune targeting with Durvalumab in combination with low-dose Lenalidomide

    The efficacy and safety of this experimental (immune) consolidation therapy during this clinical trial will be monitored by imaging changes every 8 weeks.

    Measured: up to 13 cycles (each cycle is 28 days)

  3. Immune targeting with Durvalumab in combination with low-dose Lenalidomide

    The efficacy and safety of this experimental (immune) consolidation therapy during this clinical trial will be monitored closely by tumor marker changes on Day 1 of each cycle.

    Measured: up to 13 cycles (each cycle is 28 days)

  4. Recommended dose for expansion (RDE)

    Identification of the recommended dose for expansion of Azacitidine and/or Romidepsin in combination with nab-Paclitaxel/Gemcitabine.

    Measured: at the end of cycle 3 (each cycle is 28 days)

Secondary outcomes (5)

  1. Overall response rate (ORR)

    Part 1: ORR according to RECIST version 1.1 (complete response [CR] and partial response [PR]) after respective treatment) every 6 weeks Part 2: ORR according to immune related RECIST 1.1 (irRECIST1.1) (CR and PR) after/during treatment with Lenalidomide and Durvalumab every 8 weeks

    Measured: up to 16 months

  2. Carbohydrate Antigen 19-9 (CA19-9) Response

    Part 1: CA19-9 Response: CA19 -9 change after treatment compared to baseline level Part 2: 2nd CA19-9 Response: CA19 -9 change after treatment compared to last level determined in Part 1

    Measured: at Day 1 of each treatment cycle (each cycle is 28 days), up to 16 month

  3. Disease-control rate (DCR)

    Part 1: DCR at 3-month according to RECIST version 1.1 (CR and PR and stable disease [SD] after respective treatment Part 2: 2nd DCR at 3-month and 6-month according to irRECIST1.1 (CR and PR and stable disease [SD] after respective treatment)

    Measured: at the end of cycle 3 and 6 (each cycle is 28 days)

  4. Overall survival (OS)

    Time from Day 1 of the first cycle of chemotherapy to date of death from any cause. The rate of patients who are still alive after one year will be assessed.

    Measured: at Day 1 of cycle 1 (each cycle is 28 days) until death or up to 4 years

  5. Progression free survival (PFS)

    Time from Day 1 of the first cycle of chemotherapy to date of objective disease progression or to death of any cause.

    Measured: D1 of the first cycle (each cycle is 28 days), up to 16 month

Timeline

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

  1. First posted6 Feb 2020
  2. Study start25 May 2020
  3. Primary completion2 Jul 2024
  4. Study completion2 Jul 2024

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04257448
Sponsor's protocol ID
SEPION
Other IDs
AX-CL-PANC-PI-008619
Acronym
SEPION
Status last verified
Sep 2025
First submitted
29 Jan 2020
Last updated
30 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Romidepsin, Azacitidine and nab-Paclitaxel in people with Pancreas Cancer and Pancreatic Adenocarcinoma, run by GWT-TUD GmbH at 9 sites in Germany.

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 14 inclusion and 34 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 30 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Germany. 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 combined 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.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety and tolerability of Azacitidine and/or Romidepsin in combination with nab-Paclitaxel/Gemcitabine (time frame: at Days -7, -4, 1, 8, 15, 22 at cycle 1 (each cycle is 28 days)). The study lists 4 primary outcomes in all. 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 NCT04257448.

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 30 Sep 2025.

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