Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Micronutrients

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Vitamins

Leucovorin

Fluorouracil

Irinotecan

Levoleucovorin

Durvalumab

Olaparib

Folic Acid

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Poly(ADP-ribose) Polymerase Inhibitors

Folinic Acid

Folate

Vitamin B9

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

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).

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.

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.

Arm A - Olaparib

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

ARM B - durvalumab plus selumetinib

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

ARM C FOLFIRI

Pascal HAMMEL, MD

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.

Searching for efficient maintenance therapies in metastatic PDAC patients whose disease has been controlled using an induction chemotherapy is crucial for two main reasons:

1. Patients may stop IV toxic chemotherapy while their tumor remains under control. Although up to 70% of PDAC patients achieve tumor control when treated during induction with mFOLFIRINOX, toxicity of this regimen, particularly neuropathy and fatigue, remains a key concern.
2. Tumor control may be extended, which might improve quality of life (QoL) and survival.

Patients are included in MAZEPPA study based on the genetic profile of their tumor.

* If a BRCA gene mutation is present in the tumor, treatment with the drug olaparib will be proposed (arm A), regardless of the status of the other genes analyzed.
* In the absence of a mutation in the BRCA gene and in the presence of a mutation in the KRAS gene, a treatment combining immunotherapy and targeted therapy (durvalumab and selumetinib - Arm B) or chemotherapy by FOLFIRI (arm C) will be proposed.

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.

Personalized Maintenance Therapy for m-PDAC Using Olaparib or Selumetinib + Durvalumab, Based on BRCAness and KRAS Status.

MAZEPPA: Phase II PRODIGE-GERCOR Study to Evaluate MAintenance Therapy With Olaparib or Selumetinib Plus Durvalumab According to BRCAness and KRAS Somatic Status Personalized in Metastatic Pancreatic Adenocarcinoma Patients

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).

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.

DCR is the percentage of patients who achieve CR, PR, or SD to study treatment (according to RECIST 1.1).

ORR is the number of patients with a best overall response of CR or PR divided by the number of all treated (at least 1 dose of study treatment) patients.

OS is the time between the date of inclusion into Arm A or Arms B/C and death

All grade and severe toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0

TUDD is defined as the time interval between inclusion into Arm A and randomization into Arms B/C and the first occurrence of a decrease in QLQ-C30 score for dimension ⩾5 points compared to baseline HRQoL score without any further improvement in QoL score ⩾5 points or any further available QoL data.

Spots Global Cancer Trial Database for arm c folfiri