Informations générales (source: ClinicalTrials.gov)
MegaMOST - a Multicenter, Open-label, Biology Driven, Phase II Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations /characteristics in Advanced / Metastatic Tumors. (MegaMOST)
Interventional
Phase 2
Centre Leon Berard (Voir sur ClinicalTrials)
janvier 2020
novembre 2026
13 décembre 2024
This trial is a multicenter, open-label, biology driven, phase II study using a
sequential Bayesian design, aiming to assess the efficacy and safety of different Matched
Targeted Therapy (MTT) in independent and parallel cohorts of treatment.
Patients will be assigned to a treatment cohort based on molecular
alterations/characteristics detected on tumor sample from primary tumor or metastatic
lesion.
In this protocol, several MTTs treatment cohorts are planned. This study is designed with
the flexibility to open new MTTs treatment cohorts and to close existing MTTs treatment
cohorts that demonstrate no clinical benefit. Each treatment cohort will be driven
separately even though procedures, quality control and reporting, will be common. The
protocol will be amended in order to include new treatments or combinations that emerge
as being of interest for patients with advanced/metastatic cancers.
All eligible patients will receive study drugs as long as patient experiences clinical
benefit in the opinion of the investigator, or until unacceptable toxicity, or until
symptomatic deterioration attributed to disease progression as determined by the
investigator after an integrated assessment of radiographic data and clinical status, or
withdrawal of consent.
Patients will be permitted to continue study treatment after progressive disease
according to RECIST v1.1 if they meet all of the following criteria and following
validation of the Sponsor:
- Evidence of clinical benefit as assessed by the investigators,
- Absence of symptoms and signs (including worsening of laboratory values; e.g., new
or worsening hypercalcemia) that indicate unequivocal progression of disease,
- No decline in ECOG Performance Status (PS) that can be attributed to disease
progression.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Axel LE CESNE | 18/03/2024 11:06:07 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CLCC INSTITUT CURIE | Christophe LE TOURNEAU, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine LACASSAGNE - 06189 - Nice - France | Esma SAADA-BOUZID, MD | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - 69373 - Lyon - France | Jean-Yves BLAY, MD | Contact (sur clinicalTrials) | |||
| Institut Bergonié - 33076 - Bordeaux - France | Antoine ITALIANO, PHD | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie de Strasbourg - 67033 - Strasbourg - France | Lauriane EBERST, MD | Contact (sur clinicalTrials) | |||
| Institut Paoli Calmettes - 13273 - Marseille - France | François BERTUCCI, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Male or female patients aged of at least 18 years on day of signing informed
consent.
- Patients with histologically confirmed diagnosis of metastatic disease or
unresectable locally advanced malignancy that is resistant or refractory to standard
therapies or for which standard therapies does not exist or is/are not considered
appropriate by the investigator.
- A multidisciplinary molecular board must have recommended the specific MTT based on
the following documented actionable alterations:
- Cohort HDM201-Ribociclib : amplification of CDK6 and/or CDK4, and/or CDKN2A
homozygous deletion, and/or amplification of CCND1 and/or CCND3 with no
deletion/losses more than single copy of RB1 by copy number and P53 wild-type.
- Cohort Cabozantinib : AXL, MET, VEGFR, VEGF, RET, ROS1, MER, TRKB, TIE-2 and/or
Tyro3 activating mutations and/or amplification, and/or NTRK translocation
and/or ROS1 translocation, and/or MET translocation.
- Cohort Alectinib : Activating ALK alterations: translocation, or selected
mutations
- Cohort Regoranib : Activating mutation and/or amplification of VEGFR1-3, TIE-2,
KIT, RET, RAF1, BRAF (other than V600 mutations), CRAF, HRAS, PDGFR, FGFR1-2,
FLT3 and/or CSFR1, and/or amplification of the ligands, and/or biallelic
inactivation of SMAD4
- Cohort Trametinib : Activating mutation and/or amplification of KRAS (except
all KRAS G12 mutations), NRAS, HRAS and/or MAP2K; and/or biallelic inactivation
of NF1; and/or activating mutation PTPN11; and/or amplification or
translocation of BRAF, and/or translocation RAF1
- Cohort Trametinib + Dabrafenib : BRAF V600 mutation.
- Cohort Avapritinib : Activating mutations of KIT exon 17 or PDGFRA exon 18
associated or not to mutation on KIT exon 11 or PDGFRA exon 12/14
- Previously treated by at least one prior line of treatment in the
advanced/metastatic setting.
- Documented radiological disease progression as per RECIST v1.1 and presence of at
least one measurable lesion according to RECIST 1.1 criteria based on screening
tumor assessment.
- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology
Group (ECOG) scale.
- Adequate organ function
- Adequate cardiovascular function
- Specific toxicities related to any prior anti-cancer therapy must have resolved to
grade ≤1 , except for alopecia (all grades), grade 2 neuropathy or anemia.
- Unless infertility is proven, men must agree to use effective contraception
- Women of child-bearing potential must have a negative serum pregnancy test within 7
days of first dose of study drug and agree to use effective contraception
- Patient should understand, sign, and date the written voluntary informed consent
form prior to any protocol-specific procedures performed. Patient should be able and
willing to comply with study procedures as per protocol.
- Patient must be covered by a medical insurance.
- Male or female patients aged of at least 18 years on day of signing informed
consent.
- Patients with histologically confirmed diagnosis of metastatic disease or
unresectable locally advanced malignancy that is resistant or refractory to standard
therapies or for which standard therapies does not exist or is/are not considered
appropriate by the investigator.
- A multidisciplinary molecular board must have recommended the specific MTT based on
the following documented actionable alterations:
- Cohort HDM201-Ribociclib : amplification of CDK6 and/or CDK4, and/or CDKN2A
homozygous deletion, and/or amplification of CCND1 and/or CCND3 with no
deletion/losses more than single copy of RB1 by copy number and P53 wild-type.
- Cohort Cabozantinib : AXL, MET, VEGFR, VEGF, RET, ROS1, MER, TRKB, TIE-2 and/or
Tyro3 activating mutations and/or amplification, and/or NTRK translocation
and/or ROS1 translocation, and/or MET translocation.
- Cohort Alectinib : Activating ALK alterations: translocation, or selected
mutations
- Cohort Regoranib : Activating mutation and/or amplification of VEGFR1-3, TIE-2,
KIT, RET, RAF1, BRAF (other than V600 mutations), CRAF, HRAS, PDGFR, FGFR1-2,
FLT3 and/or CSFR1, and/or amplification of the ligands, and/or biallelic
inactivation of SMAD4
- Cohort Trametinib : Activating mutation and/or amplification of KRAS (except
all KRAS G12 mutations), NRAS, HRAS and/or MAP2K; and/or biallelic inactivation
of NF1; and/or activating mutation PTPN11; and/or amplification or
translocation of BRAF, and/or translocation RAF1
- Cohort Trametinib + Dabrafenib : BRAF V600 mutation.
- Cohort Avapritinib : Activating mutations of KIT exon 17 or PDGFRA exon 18
associated or not to mutation on KIT exon 11 or PDGFRA exon 12/14
- Previously treated by at least one prior line of treatment in the
advanced/metastatic setting.
- Documented radiological disease progression as per RECIST v1.1 and presence of at
least one measurable lesion according to RECIST 1.1 criteria based on screening
tumor assessment.
- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology
Group (ECOG) scale.
- Adequate organ function
- Adequate cardiovascular function
- Specific toxicities related to any prior anti-cancer therapy must have resolved to
grade ≤1 , except for alopecia (all grades), grade 2 neuropathy or anemia.
- Unless infertility is proven, men must agree to use effective contraception
- Women of child-bearing potential must have a negative serum pregnancy test within 7
days of first dose of study drug and agree to use effective contraception
- Patient should understand, sign, and date the written voluntary informed consent
form prior to any protocol-specific procedures performed. Patient should be able and
willing to comply with study procedures as per protocol.
- Patient must be covered by a medical insurance.
- Patients amenable to therapy with curative intent.
- Patients participating to another clinical trial with a medicinal product.
- Patients previously treated with similar MTT meaning any agent targeting the same
signaling pathways components.
- Patients unable to swallow oral medication.
- Patients with known hypersensitivity to excipients
- Patients with symptomatic central nervous system (CNS) metastasis who are
neurologically unstable or require increasing doses of corticosteroids or local
CNS-directed therapy to control their CNS disease.
- Patients with secondary malignancy unless this malignancy is not expected to
interfere with the evaluation of study endpoints and is approved by the sponsor.
Examples of the latter include: basal or squamous cell carcinoma of the skin,
in-situ carcinoma of the cervix, localized prostate cancer, prior malignancy and no
evidence of recurrence for ≥ 2 years.
- Patients using, or requirement to use while on the study, or not respecting the
minimal wash-out period of medications
- Any clinically significant and/or uncontrolled medical disease that could compromise
the patient's ability to tolerate study drug or would likely interfere with study
procedures or results.
- Patients with known psychiatric or substance abuse disorders that would interfere
with cooperation with the requirements of the trial.
- Patients who are pregnant or breastfeeding women or expecting to conceive or father
children within the projected duration of the trial, starting with the screening
visit through after the last dose of trial treatment (depanding on cohort).