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

  • End date
    Mar 23, 2024
  • participants needed
  • sponsor
    GWT-TUD GmbH
Updated on 23 May 2022
measurable disease
cancer chemotherapy
ductal adenocarcinoma
pancreatic ductal adenocarcinoma
breast ductal carcinoma


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).


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

  1. 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.

Condition Pancreas Cancer, Pancreatic Adenocarcinoma, Pancreatic Ductal Adenocarcinoma
Treatment Gemcitabine, Nab-paclitaxel, Azacitidine, durvalumab, romidepsin, Lenalidomide capsule
Clinical Study IdentifierNCT04257448
SponsorGWT-TUD GmbH
Last Modified on23 May 2022


Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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
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
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