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Malignant Solid TumorPhase 2MegaMOSTNCT04116541

A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors.

A Phase 2 study testing HDM201, Ribociclib and Cabozantinib in people with Malignant Solid Tumor, run by Centre Leon Berard at 13 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Solid Tumor
What is being tested?
HDM201, Ribociclib and Cabozantinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
455 participants
Where
13 sitesFrance
Study dates
28 Jan 2020to Oct 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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, or activating rearrangements following validation by central molecular tumor board of Centre Léon Bérard.
Show all 20Show fewer
  • Cohort Regoranib : Activating mutation and/or amplification and/or rearrangement 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, following validation by central molecular tumor board of Centre Léon Bérard.
  • 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 and/or rearrangement of BRAF following validation by central molecular tumor board of Centre Léon Bérard.
  • 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 except for specific tumor type with no standard treatment approved and reimbursed in France following sponsor approval.
  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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).

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jean-Yves BLAY, MD contact

+33478785126

jean-yves.blay@lyon.unicancer.fr

Olivier TREDAN, MD contact

+33478782828

olivier.tredan@lyon.unicancer.fr

13 sites in 1 country

France13 sites, 12 recruiting

  • INSTITUT DE CANCEROLOGIE DE L'OUEST Pays de Loire

    Angers, 49055

    Pierre KUBICEK, MD, 02 41 35 27 00, pierre.kubicek@ico.unicancer.fr

    Not yet recruiting

  • Institut Bergonié

    Bordeaux, 33076

    Antoine ITALIANO, PHD, 05 56 33 32 44, a.italiano@bordeaux.unicancer.fr

    Kevin BOURCIER

    Recruiting

  • Centre François Baclesse

    Caen, 14076

    Hubert CURCIO, MD, 02 31 45 50 50, h.curcio@baclesse.unicancer.fr

    Hubert CURCIO, MD

    Recruiting

  • Centre Léon Bérard

    Lyon, 69373

    Jean-Yves BLAY, MD, 04 78 78 27 57, jean-yves.blay@lyon.unicancer.fr

    Jean-Yves BLAY, MD

    Recruiting

  • Institut Paoli Calmettes

    Marseille, 13273

    François BERTUCCI, MD, 04 91 22 35 37, bertuccif@ipc.unicancer.fr

    Anthony GONCALVES, MD, 04 91 22 37 89, goncalvesa@ipc.unicancer.fr

    Recruiting

  • Centre Antoine LACASSAGNE

    Nice, 06189

    Esma SAADA-BOUZID, MD, 04 92 03 15 14, esma.saada-bouzid@nice.unicancer.fr

    Esma SAADA-BOUZID, MD

    Recruiting

  • Institut Curie

    Paris, 75248

    Christophe LE TOURNEAU, MD, 01 44 32 46 75, christophe.letourneau@curie.fr

    Delphine LOIRAT, MD, 01 44 32 46 75, delphine.loirat@curie.fr

    Not yet recruiting

  • Centre Henri Becquerel

    Rouen, 76038

    Maxime FONTANILLES, MD, 02 32 08 22 22, maxime.fontanilles@chb.unicancer.fr

    Not yet recruiting

  • Centre Paul Strauss

    Strasbourg, 67033

    Teresa AMARAL, MD, 03 68 76 68 70, t.amaral@institut-strauss.fr

    Recruiting

  • Institut de Cancérologie de Strasbourg

    Strasbourg, 67033

    Terminated

  • CHU Strasbourg - Hôpital de Hautepierre

    Strasbourg, 67098

    Lauriane Eberst, MD, 03 68 76 71 68, l.eberst@icans.eu

    Lauriane EBERST, MD

    Recruiting

  • Institut Claudius Regaud

    Toulouse, 31059

    Carlos-Alberto GOMEZ-ROCA, MD, 05 31 15 51 01, gomez-roca.carlos@iuct-oncopole.fr

    Jean-Pierre DELORD, MD, 05 31 15 51 01, delord.jean-pierre@iuct-oncopole.fr

    Recruiting

  • Institut Gustave Roussy

    Villejuif, 94805

    Axel LE CESNE, PhD, 01 42 11 43 16, axel.lecesne@gustaveroussy.fr

    Rastislav BAHLEDA, MD

    Recruiting

Other trials in France

About this study

Official title: 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.

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.

Read more

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.
Being tested
HDM201, Ribociclib, Cabozantinib, Alectinib, Regorafenib
Keywords
Metastatic Solid Neoplasm, Advanced Solid Tumor, Genomic alteration, Targeted therapy, Cabozantinib, Ribociclib, HDM201, Alectinib, Trametinib, Dabrafenib, Avapritinib
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HDM201Drug

    Also called Closed cohort

    HDM201 120mg, Every 3 weeks, Per os

  • RibociclibDrug

    Also called Closed cohort

    Ribociclib 200mg/day, once daily 2 weeks on/1 week off, Per os

  • CabozantinibDrug

    Also called Closed cohort

    Cabozantinib, 60 mg /day, continuous, Per os

  • AlectinibDrug

    Also called Open cohort

    Alectinib, 600mg twice daily, Per os

  • RegorafenibDrug

    Also called Closed cohort

    Regorafenib 160mg, once daily, 3 weeks on/1 week off, Per os

  • TrametinibDrug

    Also called Closed cohort

    Trametinib 2 mg/day, continuous, Per os

  • DabrafenibDrug

    Also called Open cohort

    Dabrafenib 150 mg twice daily, Per os

  • AvapritinibDrug

    Also called Open cohort

    300 mg/day,continuous, Per os

Study groups in NCT04116541
Study groupRoleWhat they receive
HDM201 + RibociclibExperimentalPatient with documented amplification of Cyclin-dependent kinase 6 (CDK6) and/or Cyclin-dependent kinase 4 (CDK4), and/or cyclin dependent kinase inhibitor 2A (CDKN2A) homozygous deletion, and/or amplification of Cyclin D1 (CCND1) and/or Cyclin D3 (CCND3) with no deletion/losses more than single copy of retinoblastoma 1 (RB1) by copy number and P53 wild-type detected on tumor sample from primary tumor or metastatic lesion.
Receives: Drug: HDM201; Drug: Ribociclib
CabozantinibExperimentalPatient with AXL, MET, vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor (VEGF), RET, ROS1, MER, Tropomyosin receptor kinase B (TRKB),TIE-2 and/or Tyro3 activating mutations and/or amplification, and/or NTRK translocation and/or ROS1 translocation, and/or MET translocation detected on tumor sample from primary tumor or metastatic lesion.
Receives: Drug: Cabozantinib
AlectinibExperimentalActivating ALK alterations: translocation, or selected mutations,), or activating rearrangements following validation by central molecular tumor board of Centre Léon Bérard.
Receives: Drug: Alectinib
RegorafenibExperimentalPatient with Activating mutation and/or amplification and/or rearrangement of VEGFR1-3, TIE-2, KIT, RET, RAF1, BRAF (other than V600 mutations), CRAF, HRAS , PDGFR, FGFR1-2, FLT3 and/or CSF1R, and/or amplification of the ligands, and/or biallelic inactivation of SMAD4, following validation by central molecular tumor board of Centre Léon Bérard.
Receives: Drug: Regorafenib
TrametinibExperimentalPatient with activating mutation and/or amplification of KRAS (except all KRAS G12 mutations), NRAS, HRAS and/or Mitogen-Activated Protein Kinase Kinase (MAP2K); and/or biallelic inactivation of Neurofibromin 1 (NF1); and/or activating mutation Protein Tyrosine Phosphatase Non-Receptor Type 11 (PTPN11); and/or amplification or translocation of BRAF ; and/or translocation RAF1
Receives: Drug: Trametinib
Trametinib + DabrafenibExperimentalPatient with BRAF V600 mutation and/or rearrangement of BRAF following validation by central molecular tumor board of Centre Léon Bérard
Receives: Drug: Trametinib; Drug: Dabrafenib
AvapritinibExperimentalActivating mutations of KIT exon 17 or PDGFRA exon 18 associated or not to mutation on KIT exon 11 or PDGFRA exon 12/14
Receives: Drug: Avapritinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free rate after 3 months (12 weeks) of treatment

    The proportion of patients with a complete response (CR), a partial response (PR) or a stable disease (SD) at 3 months (12 weeks).

    Measured: 3 months (12 weeks)

Secondary outcomes (6)

  1. Objective response rate after 3 months (12 weeks) of treatment

    The proportion of patients with a complete or a partial response (CR or PR) as best overall response at 3 months (12 weeks).

    Measured: 3 months (12 weeks)

  2. Duration of Response

    Duration of response applies only to patients whose best overall response was a complete response or a partial response (CR or PR). It will be defined as the time from the date of first documented response (CR or PR) to the date of the first documented progression or death due to underlying cancer and censored at the date of the last adequate tumor assessment.

    Measured: Up to 3 years

  3. Progression Free Survival

    The time from the date of the first study drug administration to the first documented progression according to investigator assessment of RECIST version 1.1 or death due to any cause

    Measured: Up to 3 years

  4. Overall survival

    The time from the date of the first study drug administration to the date of death due to any cause

    Measured: Up to 3 years

  5. Percentage of long-term responders (> 6 months)

    The proportion of long term responders (> 6 months)

    Measured: 6 months

  6. Adverse Events

    Nature, frequency and severity of Adverse Events (AEs), Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs) graded using Common Terminology Criteria for Adverse Events (CTCAE) V5.0.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Oct 2019
  2. Study start28 Jan 2020
  3. Primary completionOct 2026 (estimated)
  4. Study completionOct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
455 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04116541
Sponsor's protocol ID
ET19-073 (MegaMOST)
Other IDs
2023-510567-35-00, 2019-001494-88, 2019, 2023
Acronym
MegaMOST
Status last verified
Jul 2026
First submitted
1 Oct 2019
Last updated
8 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing HDM201, Ribociclib and Cabozantinib in people with Malignant Solid Tumor, run by Centre Leon Berard at 13 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jean-Yves BLAY, MD (+33478785126, jean-yves.blay@lyon.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free rate after 3 months (12 weeks) of treatment (time frame: 3 months (12 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04116541.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.

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