Maintenance With Olaparib or Selumetinib + Durvaluma for m-PDAC Guided by BRCAness and KRAS Status.

NCT04348045 | Active Not Recruiting Phase 2

• 1 other identifier: MAZEPPA D19-02 PRODIGE-72
• Study Type: interventional
• Target: 307
• Locations: 1 country
• Sites: 29

Brief Summary

MAZEPPA is open-label, phase II study to assess the efficacy of a genomic-driven maintenance therapy in terms of PFS in Pancreatic ductal adenocarcinoma (PDAC) patients with disease controlled after 4 months of mFOLFIRINOX chemotherapy as following: Patients with a BRCAness somatic profile: olaparib Arm A. Patients with no BRCAness profile and with KRAS mutation randomization between durvalumab plus selumetinib Arm B, versus FOLFIRI Arm C.

Conditions

Metastatic Pancreatic Adenocarcinoma

Keywords

BRCAness status; KRAS somatic status

Outcome Measures

Primary Outcomes (2)

• ARM A - Progression free survival (PFS)

  PFS rate at 4 months is defined by the number of patients alive at 4 months from inclusion without PD divided by the total number of patients evaluable at 4 months (dead during 4 months or alive at 4 months with a progressive status available).

  at 4 months

• ARM B/ C - PFS

  PFS is defined as time from randomization into arm B/C to the date of first documented PD RECIST 1.1 and/or iRECIST for arm B and PD RECIST1.1 for arm C or death.

  Assessed up to 36 months

Secondary Outcomes (5)

• Disease control rate (DCR)

  Measured at 16 weeks of maintenance therapy.

• Overall response rate (ORR)

  Assessed up to 36 months

• Overall survival (OS)

  Assessed up to 36 months

• Number of participants with treatment-related adverse events

  Assessed up to 36 months

• Time to HRQoL score definitive deterioration (TUDD)

  At baseline, at every 2 months during treatment, and at the end of treatment visit. Assessed up to 36 months

Study Arms (3)

ARM A - olaparib

EXPERIMENTAL

Olaparib tablets at 300 mg orally twice daily until PD (RECIST 1.1) or unacceptable toxicity.

Drug: Arm A - Olaparib

ARM B - durvalumab plus selumetinib

EXPERIMENTAL

Durvalumab plus selumetinib until PD (RECIST 1.1 and/or iRECIST), unacceptable toxicity, withdrawal of consent, or death. Durvalumab administered IV at a flat dose of 1500 mg on day 1 of every 28-day cycle, Selumetinib administered as 75 mg twice daily dose for 21 days on and 7 days off (a 28-day cycle).

Drug: ARM B - durvalumab plus selumetinib

ARM C - FOLFIRI

ACTIVE COMPARATOR

FOLFIRI FOLFIRI (irinotecan 180 mg/m2 IV on day 1, folinic acid 400 mg/m2 IV on day 1, 5-FU 400 mg/m2 IV bolus on day 1 and 2, and 46h IV infusion of 5-FU 2400 mg/m2 every 2 weeks) until PD (RECIST 1.1) unacceptable toxicity, withdrawal of consent, or death.

Drug: ARM C FOLFIRI

Interventions

Arm A - Olaparib DRUG

300 mg orally twice daily, for a total daily dose of 600mg Study treatment can be dose-reduced to : First step : 250 mg twice daily , for a total daily dose of 500 mg Second step: 200 mg twice daily taken twice daily, for a total daily dose of 400 mg No further dose reduction is allowed, and study treatment should be discontinued.

Also known as: AZD-2281

ARM A - olaparib

ARM B - durvalumab plus selumetinib DRUG

Durvalumab administered IV at a flat dose of 1500 mg on day 1 of every 28-day cycle, Selumetinib Starting Dose : 75 mg twice daily Study treatment can be dose-reduced to : Dose Level -1 : 75 mg once daily Dose Level -2 : 50 mg twice daily Dose Level -3 : 50 mg once daily

Also known as: MEDI-4736 plus AZD-6244

ARM B - durvalumab plus selumetinib

ARM C FOLFIRI DRUG

FOLFIRI every two weeks Irinotecan 180 mg/m2 Intravenous (IV) on day 1 Folinic acid 400 mg/m2 IV on day 1, 5-FU 400 mg/m2 IV bolus on day 1 and 2, and 46h IV infusion of 5-FU 2400 mg/m2

Also known as: folinic acid, fluorouracil, and irinotecan

ARM C - FOLFIRI

Eligibility Criteria

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

You may qualify if:

• Signed and dated informed consent,
• Age ≥18 years
• Body weight \>30 kg,
• 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,
• Life expectancy of at least 4 months,
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1,
• Pathologically confirmed pancreatic adenocarcinoma with distant metastases (stage IV disease),
• No prior therapy for metastatic disease other than mFOLFIRINOX (in case of previous adjuvant therapy, the interval between the end of adjuvant chemotherapy and relapse must be \>6 months),
• Stability or tumor response (Response evaluation criteria in solid tumors \[RECIST\] 1.1) after 4 months of mFOLFIRINOX (8 cycles) for metastatic disease,
• Have tissue from archival tissue sample from surgery or biopsy identified and confirmed as available for study
• Availability of tumor somatic genetic analyses data, performed during the first 4 months of mFOLFIRINOX (specific informed consent),
• At least one measurable or evaluable lesion as assessed by CT-scan or MRI according to RECIST 1.1 and feasibility of repeated radiological assessments,
• Normal organ and bone marrow function prior to administration of study treatment as defined below:
• Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days,
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L,

You may not qualify if:

• Histology other than PDAC
• Toxicities after mFOLFIRINOX treatment not resolved to ≥ grade 1 prior to maintenance treatment, except for oxaliplatin induced neuropathy, alopecia, or grade ≥ 2 are permitted
• Enrollment in another therapeutic trial
• Evidence of interstitial lung disease, any active non-infectious pneumonitis, or known active infection including active tuberculosis
• Hepatitis B virus (HBV; known positive HBV surface antigen (HbsAg) result), hepatitis C virus (HCV), or human immunodeficiency virus (positive HIV ½ antibodies).
• Active uncontrolled infection, current unstable, or uncompensated respiratory or cardiac conditions, or active digestive hemorrhages less than 3 months,
• Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study,
• Live vaccine administration within 30 days prior to the first dose of study treatment,
• Treatment with any other investigational medicinal product within 28 days prior to study entry,
• Other malignancy unless curatively treated with no evidence of disease for ≥ 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), and stage 1, grade 1 endometrial carcinoma,
• Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, acute coronary syndrome within 6 months prior to starting treatment, prior or current cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent,
• Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the Investigator or patients with congenital long QT syndrome. Mean corrected QT interval (QTc) for heart rate using the QTcF formula ≥ must be \<470 ms,
• Pregnancy/lactation,
• Uncontrolled massive pleural effusion or massive ascites,
• Tutelage or guardianship.

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead
• AstraZeneca: collaborator

Study Sites (29)

Institut Sainte Catherine

Avignon, France

Location

CHRU Jean Minjoz

Besançon, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Hôpital Beaujon

Clichy, France

Location

GHPSO Site de Creil

Creil, France

Location

Centre Georges François Leclerc

Dijon, France

Location

CHU Dijon

Dijon, France

Location

CHU Grenoble Alpes Hôpital Michallon

Grenoble, France

Location

Hôpital Franco-Britannique

Levallois-Perret, France

Location

CHRU Lille

Lille, France

Location

centre Léon Bérard

Lyon, France

Location

Hôpital Privé Jean Mermoz

Lyon, France

Location

Hôpital Saint Joseph Saint Luc

Lyon, France

Location

CHU La Timone

Marseille, France

Location

Hôpital Européen

Marseille, France

Location

Institut Paoli Calmette

Marseille, France

Location

Hôpital Nord Franche Comté

Montbéliard, France

Location

GH Diaconesses Croix Saint Simon

Paris, France

Location

Hôpital Européen Georges Pompidou

Paris, France

Location

Hôpital Pitié Salpêtrière

Paris, France

Location

Hôpital Saint Antoine

Paris, France

Location

Institut Mutualiste Montsouris

Paris, France

Location

CHU Poitiers

Poitiers, France

Location

CHU Robert Debré

Reims, France

Location

ICO Site de Saint Herblain

Saint-Herblain, France

Location

Centre Paul Strauss

Strasbourg, France

Location

CHU Toulouse IUCT Rangueil

Toulouse, France

Location

Hôpital Trousseau

Tours, France

Location

MeSH Terms

Interventions

olaparib; AZD 6244; durvalumab; Leucovorin; Fluorouracil; Irinotecan

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids

Study Officials

• Pascal HAMMEL, MD

  Hôpital Beaujon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients with a BRCAness somatic profile: olaparib Arm A. Patients with no BRCAness profile and with KRAS mutation randomization between durvalumab plus selumetinib Arm B, versus FOLFIRI Arm C.

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: April 15, 2020
• Study Start: December 7, 2020
• Primary Completion: June 15, 2023
• Study Completion: December 1, 2025
• Last Updated: July 25, 2025

Record last verified: 2025-07

Locations

FR (29)