Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment

Sponsor
Centre Leon Berard
Study ID
NCT02029001
Phase
PHASE2
Status
Recruiting
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Conditions

  • Malignant Solid Neoplasms

Eligibility Criteria

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

Interventions

  • Nilotinib (400 mg BID) — DRUG
    Patient with advanced pigmented villonodular synovitis and tumors with mutations of ABL1, KIT, PDGFRA, PDGFRB, DDR1, DDR2, CSF1R, or amplification/translocation of the genes and/or of the ligands.
  • Everolimus (10 mg QD) — DRUG
    Patients whose tumor harbors mutations or amplification of the PIK3CA, PIK3R1, AKT1, AKT2, mTOR, RICTOR, RAPTOR genes, or with TSC1, TSC2 or PTEN loss (defined as complete loss of both gene copies OR loss of one copy + mutation on the other copy or loss of one copy + loss of expression using immunohistochemistry).
  • Sorafenib (400 mg BID) — DRUG
    Patients whose tumor harbors mutations of VEGFR1-3, PDGFRB, FLT3, BRAF (other than V600 mutations), CRAF, HRAS, KRAS or RET or amplification/translocation of the genes and/or of the ligands.
  • Lapatinib (1500 mg QD) — DRUG
    Patients whose tumor harbors mutations or amplifications of HER2
  • Pazopanib (800 mg QD) — DRUG
    Patients whose tumor harbors mutations of VEGFR1-3, PDGFRA, PDGFRB or KIT\* or amplification /translocation of the genes and/or of the ligands.
  • Olaparib (300 mg BID) — DRUG
    ATM, BAP1 et BRIP1 Mutation only if double hit documented; BRCA2, BRCA1, RAD51C, PALB2, RAD51D Mutation; BRCA1, BRCA2, ATM and BAP1 Loss; BRCA1, BRCA2, ATM and BAP 1 : mutation and heterozygote deletion. except for patients eligible to olaparib's available labels and reimbursements in France. NOTE : only prostate cancer with RECIST 1.1 evaluable disease are eligible until the French price and reimbursement
  • Durvalumab + Tremelimumab — COMBINATION_PRODUCT
    Any molecular types of tumor (which are known to be immunogenic or with high mutation load), except lung, urothelial and head and neck or CNS tumors, or patients who fulfill conditions to receive any other MTT of the MOST Plus study.

Study Details

The MOST Plus study is a two-period phase II clinical trial, conducted in patients with all types of progressive solid tumors after at least 1 prior systemic treatment regimen for advanced disease (in the absence of a validated second line therapy). The main goal of this study is to evaluate for these patients the clinical benefit of a maintenance treatment in patients with stable disease (SD) after induction treatment with a selected therapy (Molecular Targeted Therapy (MTT) or with SD, partial response (PR) or complete reponse (CR) with Immunotherapy (IT)). For MTT, the first period of this trial (induction period) will enable to establish whether the identification of genomic alterations in genes encoding for "actionable" targets in the tumor cells, regardless of the histological subtype, can be used to select efficient treatment targeting the pathway activated by the mutation. For Immunotherapy, induction period with durvalumab + tremelimumab is expected to be an innovative therapy for an efficient tumor control and may allow to identify types of cancer or molecular types of cancer that are more receptive to immunotherapy. For all treatments, the second period (maintenance period) will use a randomized design to evaluate the clinical benefit of a maintenance treatment with the targeted therapy or immunotherapy selected based on tumor molecular profile in patients treated by MTT with SD and in patients treated by IT with SD, PR or CR. Each patient enrolled will receive the matching targeted therapy during 12 weeks (MTT) or 52 weeks (IT). At the end of this induction period: MTT cohorts : * patients with a tumor response (CR: complete response or PR: partial response) will continue the targeted therapy, * patients in progression will discontinue the targeted therapy and will be withdrawn from study and oriented towards standard treatments * patients with a stable disease at 12 weeks will be randomized in order to determine if they continue or stop the therapy. IT cohort : \- patients with SD, PR or CR at 52 weeks will be randomized in order to determine if they continue or stop the therapy. For each MTT treatment group: \~80 patients treated in the first step (induction period), 50 patients randomized in the second step (maintenance period, 25 patients per arm). For IT treatment group: \~125 patients treated in the first step (induction period), 50 patients randomized in the second step (maintenance period, 25 patients per arm). In total (for 7 treatment groups): \~ 900 patients treated in the induction period and 350 patients randomized in maintenance period.

Key Dates

Start date
Mar 31, 2014
Status verified
Aug 2025
Primary completion
Jan 31, 2026
Completion
Oct 31, 2027

Study Design

Enrollment
900 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A: Maintenance treatment
    Patients will continue targeted treatment matching the molecular alterations identified in their tumor * for a maximum of 136 weeks starting from the date of patient's first study drug intake following inclusion or a discontinuation criteria (unacceptable toxicity, interruption of study drug more than 28 days, documented on-treatment disease progression, patient decision, investigator decision, pregnancy) is met for nilotinib, everolimus, sorafenib, lapatinib, pazopanib, olaparib. * until loss of clinical benefit, or until a permanent study drug discontinuation criteria is met (unacceptable toxicity, interruption of study drug more than 28 days, documented on-treatment disease progression, patient decision, investigator decision, pregnancy) or for up to 2 years duration for patients with CR/PR/SD with the possibility of rechallenge in case of PD after IT cessation for durvalumab + tremelimumab
  • No Intervention: Arm B:Interruption of targeted treatment
    Targeted treatment received during induction period will be discontinued until a first documented off-treatment disease progression occurs. At progression, treatment reintroduction may be proposed to the patient (left at the investigator's appreciation, and upon patient approval). Treatment may be continued until on-treatment disease progression, unacceptable toxicity or for a maximum of 136 weeks from the date of patient's first study drug intake following inclusion for nilotinib, everolimus, sorafenib, lapatinib, pazopanib, olaparib or until loss of clinical benefit, or until a permanent study drug discontinuation criteria is met for durvalumab + tremelimumab. If the investigator considers that the treatment cannot be safely reintroduced (regarding patient's condition and/or laboratory results), the patient will be withdrawn from study.

Primary Outcome Measure

Induction Progression-Free Rate after induction treatment [ Time Frame: 12 weeks for MTT or 52 weeks for IT after initiation of study treatment ]

Central Contacts