Phase II Study to Evaluate MAintenance Therapy With Olaparib or Selumetinib Plus Durvalumab According to BRCAness and KRAS Somatic Status Personalized in Metastatic Pancreatic Adenocarcinoma Patients (D19-02)
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|ClinicalTrials.gov Identifier: NCT04348045|
Recruitment Status : Recruiting
First Posted : April 15, 2020
Last Update Posted : December 30, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Pancreatic Adenocarcinoma||Drug: Arm A - Olaparib Drug: ARM B - durvalumab plus selumetinib Drug: ARM C FOLFIRI||Phase 2|
Searching for efficient maintenance therapies in metastatic PDAC patients whose disease has been controlled using an induction chemotherapy is crucial for two main reasons:
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||307 participants|
|Intervention Model:||Factorial Assignment|
|Intervention Model Description:||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.|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||December 7, 2020|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||December 2023|
Experimental: ARM A - olaparib
Olaparib tablets at 300 mg orally twice daily until PD (RECIST 1.1) or unacceptable toxicity.
Drug: Arm A - Olaparib
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.
Experimental: ARM B - durvalumab plus selumetinib
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
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
Active Comparator: ARM C - FOLFIRI
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
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 A - Progression free survival (PFS) [ Time Frame: at 4 months ]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).
- ARM B/ C - PFS [ Time Frame: Assessed up to 36 months ]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.
- Disease control rate (DCR) [ Time Frame: Measured at 16 weeks of maintenance therapy. ]DCR is the percentage of patients who achieve CR, PR, or SD to study treatment (according to RECIST 1.1).
- Overall response rate (ORR) [ Time Frame: Assessed up to 36 months ]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.
- Overall survival (OS) [ Time Frame: Assessed up to 36 months ]OS is the time between the date of inclusion into Arm A or Arms B/C and death
- Number of participants with treatment-related adverse events [ Time Frame: Assessed up to 36 months ]All grade and severe toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
- Time to HRQoL score definitive deterioration (TUDD) [ Time Frame: At baseline, at every 2 months during treatment, and at the end of treatment visit. Assessed up to 36 months ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04348045
|Contact: Pascal HAMMEL, MD||01 40 29 85 firstname.lastname@example.org|
|Contact: Marie-Line GARCIA LARNICOL, MD||01 40 29 85 email@example.com|
|Principal Investigator:||Pascal HAMMEL, MD||Hôpital Beaujon|