Klinische Studien

SEPION

AcronymISRCTNEudraCTNCT (clinicaltrials.gov)DRKS
2017-001625-40NCT04257448

A multi-center, PHASE I/II STUDY OF SEQUENTIAL EPIGENETIC AND IMMUNE TARGETING IN COMBINATION WITH NAB-PACLITAXEL/GEMCITABINE IN PATIENTS WITH ADVANCED PANCREATIC DUCTAL ADENOCARCINOMA (SEPION)

Status: Active

Purpose / Objectives

Primary Outcome

The primary objective of the study, including the dose escalating part (Part 1a), the dose expansion part (Part 1b) as well as the consolidation part (Part 2), is to determine the safety and tolerability of Azacitidine (according to visit schedule Arm B) and/or Romidepsin (according to visit schedule Arm A) in combination with nab-Paclitaxel/Gemcitabine in patients with advanced PDAC (Part 1a and 1b), followed by sequential immune targeting with PD-L1 blockade in combination with low-dose Lenalidomide (Part 2) in patients with controlled disease after 3 cycles (Part 1).
Moreover, in the dose escalating part of the study (Part 1a), the recommmended dose for expansion (RDE) and dose-limiting toxicity (DLT) of Azacitidine and/or Romidepsin in combination with nab-Paclitaxel/Gemcitabine will be identified.

Secondary Outcomes

• to assess ORR, CA19-9 response and disease control rate (= 1st DCR after 3 cycles), progression free survival (PFS) and overall survival (OS) in patients treated at the recommended dose and regimen of Azacitidine and/or Romidepsin in combination with nab-Paclitaxel/Gemcitabine (Part 1a and Part 1b)
• to show a promising clinical activity (refer to 4.2.2) of the selected epigenetic and chemotherapeutic targeting approach from Part 1a with regard to the disease control rate (Part 1b)
• to assess 2nd ORR, 2nd CA19-9 response and 2nd DCR (after start of Part 2), PFS and OS in patients treated with Durvalumab and Lenalidomide as consolidation treatment (Part 2)
• to assess OS in all patients treated at the recommended dose and regimen

Diagnosis

ADVANCED PANCREATIC DUCTAL ADENOCARCINOMA

Adult patients (≥18 years) with Pancreatic Ductal Adenocarcinoma (PDAC)
• metastatic disease (stage IV) and have 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 IMiDs (Lenalidomide)

Target population

Stage

IB/II

Inclusion criteria

1. Patients must have histologically confirmed PDAC
2. Patients must have metastatic disease (stage IV) and not received prior chemotherapy for stage IV disease (adjuvant/additive chemotherapy is allowed if completed at least 6 months prior to study inclusion)
3. Patients must not have received the following drugs before: Azacitidine, Romidepsin, any checkpoint-inhibitor or immunomodulating agents such as IMiDs (Lenalidomide)
4. 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
5. Male or female, age > 18 years
6. Body weight > 30 kg for inclusion into Part 2 (according to Durvalumab treatment)
7. ECOG performance status 0 or 1
8. Patients must have normal organ and marrow function as defined below
• Leukocytes ≥ 2,5 x 109/L
• Absolute neutrophil count ≥ 1,5 x 109/L
• Platelets ≥ 100 x 109/L
• Haemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
• Asparate aminotransferase/alanine aminotransferase (AST/ALT) (SGOT/SGPT) ≤ 2.5 x ULN and ≤ 5 in the case of liver metastasis
• Measured creatinine clearance (CL) >60 mL/min or calculated creatinine CL>60 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance
9. Patients must be recovered from the effects of any prior surgery
10. 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

Exclusion criteria

1. 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
2. Patients may not be receiving any other investigational agents.
3. Patients who have previously received Romidepsin, Azacitidine, Lenalidomide or Durvalumab or any PD1 or PD-L1 inhibitor or participate currently on an other clinical trial, unless it is an observational (non-interventinal) clinical study or during the follow-up period of an interventional study
4. Patients with untreated or uncontrolled brain metastases or leptomeningeal disease
5. Presence of other active illnesses
6. Any known cardiac abnormalities such as:
• Congenital long QT syndrome
• QTc interval ≥ 470 milliseconds. Calculated from 3 ECGs using Fridericias Correction
7. Myocardial infarction within 6 months of C1D1. Subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate

Study design

  • Phase II
  • Multicenter
  • Open Label

Documents (password protected)

Responsibilities in overall study

AstraZeneca GmbH

    Study Sites

    Med. Klinik 5 Onkologie/Hämatologie - Klinikum Nürnberg

    Address
    Med. Klinik 5 Onkologie/Hämatologie - Klinikum Nürnberg
    Klinikum Nürnberg Nord
    Prof.-Ernst-Nathan-Str. 1
    90419 Nürnberg
    Haus: Bau 12

    Status

    Active (Recruitment Closed)

    Principal Investigator

    Dr. med. Gabriele Siegler

    Contact at Site

     
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