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

NCT04257448 | Completed Phase 1 DMC

• 2 other identifiers: SEPIONAX-CL-PANC-PI-008619
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 9

Brief 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 (PD-L)1 blockade in combination with low-dose Lenalidomide (Part 2) in patients with controlled disease after 3 cycles (Part 1).

Conditions

Pancreas Cancer; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (4)

• 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.

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

• 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.

  up to 13 cycles (each cycle is 28 days)

• 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.

  up to 13 cycles (each cycle is 28 days)

• Recommended dose for expansion (RDE)

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

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

Secondary Outcomes (5)

• Overall response rate (ORR)

  up to 16 months

• Carbohydrate Antigen 19-9 (CA19-9) Response

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

• Disease-control rate (DCR)

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

• Overall survival (OS)

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

• Progression free survival (PFS)

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

Study Arms (6)

Romidepsin/nab-Paclitaxel/Gemcitabine (Arm A)

EXPERIMENTAL

Part 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.

Drug: Romidepsin; Drug: nab-Paclitaxel; Drug: Gemcitabine

Azacitidine/nab-Paclitaxel/Gemcitabine (Arm B)

EXPERIMENTAL

Part 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.

Drug: Azacitidine; Drug: nab-Paclitaxel; Drug: Gemcitabine

Romidepin/Azacitidine/nab-Paclitaxel/Gemcitabine (Arm C)

EXPERIMENTAL

Part 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.

Drug: Romidepsin; Drug: Azacitidine; Drug: nab-Paclitaxel; Drug: Gemcitabine

nab-Paclitaxel/Gemcitabine (Standard Arm)

ACTIVE COMPARATOR

nab-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.

Drug: nab-Paclitaxel; Drug: Gemcitabine

Arm C or B or A

EXPERIMENTAL

In 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).

Drug: Romidepsin; Drug: Azacitidine; Drug: nab-Paclitaxel; Drug: Gemcitabine

Durvalumab/Lenalidomide

EXPERIMENTAL

Part 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.

Drug: Durvalumab; Drug: Lenalidomide capsule

Interventions

Romidepsin DRUG

Powder and solvent for solution for infusion; Intravenous use

Also known as: Istodax

Arm C or B or A; Romidepin/Azacitidine/nab-Paclitaxel/Gemcitabine (Arm C); Romidepsin/nab-Paclitaxel/Gemcitabine (Arm A)

Azacitidine DRUG

Powder for suspension for injection; Subcutaneous use

Also known as: Vidaza

Arm C or B or A; Azacitidine/nab-Paclitaxel/Gemcitabine (Arm B); Romidepin/Azacitidine/nab-Paclitaxel/Gemcitabine (Arm C)

nab-Paclitaxel DRUG

Powder for suspension for injection; Intravenous use

Also known as: Abraxane

Arm C or B or A; Azacitidine/nab-Paclitaxel/Gemcitabine (Arm B); Romidepin/Azacitidine/nab-Paclitaxel/Gemcitabine (Arm C); Romidepsin/nab-Paclitaxel/Gemcitabine (Arm A); nab-Paclitaxel/Gemcitabine (Standard Arm)

Gemcitabine DRUG

Powder for solution for infusion; Intravenous use

Arm C or B or A; Azacitidine/nab-Paclitaxel/Gemcitabine (Arm B); Romidepin/Azacitidine/nab-Paclitaxel/Gemcitabine (Arm C); Romidepsin/nab-Paclitaxel/Gemcitabine (Arm A); nab-Paclitaxel/Gemcitabine (Standard Arm)

Durvalumab DRUG

Concentrate for solution for infusion; Intravenous use

Also known as: Imfinzi

Durvalumab/Lenalidomide

Lenalidomide capsule DRUG

Hard capsule for oral use

Also known as: Revlimid

Durvalumab/Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GWT-TUD GmbH: lead
• Celgene: collaborator
• AstraZeneca: collaborator

Study Sites (9)

Uniklinik Köln

Cologne, 50937, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Universitätsmedizin Göttingen

Göttingen, 37075, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20251, Germany

Location

Ludwig-Maximilians-Universität München

München, 81377, Germany

Location

Klinikum Nürnberg

Nuremberg, 90419, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

romidepsin; Azacitidine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine; durvalumab; Lenalidomide

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Deoxycytidine; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jens Siveke, Prof. Dr.

  Institute for Developmental Cancer Therapeutics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2020
• First Posted: February 6, 2020
• Study Start: May 25, 2020
• Primary Completion: July 2, 2024
• Study Completion: July 2, 2024
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (9)