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

Sponsor
GWT-TUD GmbH
Study ID
NCT04257448
Phase
PHASE1/PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Romidepsin — DRUG
    Powder and solvent for solution for infusion; Intravenous use
  • Azacitidine — DRUG
    Powder for suspension for injection; Subcutaneous use
  • nab-Paclitaxel — DRUG
    Powder for suspension for injection; Intravenous use
  • Gemcitabine — DRUG
    Powder for solution for infusion; Intravenous use
  • Durvalumab — DRUG
    Concentrate for solution for infusion; Intravenous use
  • Lenalidomide capsule — DRUG
    Hard capsule for oral use

Study Details

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).

Key Dates

Start date
May 25, 2020
Status verified
Sep 2025
Primary completion
Jul 2, 2024
Completion
Jul 2, 2024

Study Design

Enrollment
75 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Romidepsin/nab-Paclitaxel/Gemcitabine (Arm A)
    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.
  • Experimental: Azacitidine/nab-Paclitaxel/Gemcitabine (Arm B)
    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.
  • Experimental: Romidepin/Azacitidine/nab-Paclitaxel/Gemcitabine (Arm C)
    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.
  • Active Comparator: nab-Paclitaxel/Gemcitabine (Standard Arm)
    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.
  • Experimental: Arm C or B or A
    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).
  • Experimental: Durvalumab/Lenalidomide
    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.

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) ]

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