Description:
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.
Title
- Brief Title: A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors.
- 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.
Clinical Trial IDs
- ORG STUDY ID:
ET19-073 (MegaMOST)
- SECONDARY ID:
2019-001494-88
- NCT ID:
NCT04116541
Conditions
Interventions
Drug | Synonyms | Arms |
---|
HDM201 | | HDM201 + Ribociclib |
Ribociclib | | HDM201 + Ribociclib |
Cabozantinib | | Cabozantinib |
Alectinib | | Alectinib |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
HDM201 + Ribociclib | Experimental | Patient 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. | |
Cabozantinib | Experimental | Patient with AXL, MET, vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor (VEGF), KIT, RET, ROS1, MER, Tropomyosin receptor kinase B (TRKB), Fms-like tyrosine kinase 3 (FLT3), TIE-2 and/or Tyro3 activating mutations and/or amplification, and/or NTRK translocation detected on tumor sample from primary tumor or metastatic lesion. | |
Alectinib | Experimental | Patient with ALK alterations: translocation, mutation or amplification | |
Eligibility Criteria
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, KIT, RET, ROS1, MER, TRKB, FLT3,
TIE-2 and/or Tyro3 activating mutations and/or amplification, and/or NTRK
translocation
- Cohort Alectinib : Activating ALK alterations: translocation, mutation or
amplification
- 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.
Exclusion Criteria:
- 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 (4 weeks for anti-cancer systemic treatment,
Chemotherapy, Radiotherapy, Surgery, Live vaccines ; 2 weeks for Growth Factors
targeting the myeloid lineage; 1 week for medication known to prolong the QT interval,
Strong inducers or inhibitors of CYP3A4/5, Oral anticoagulants)
- Known Human Immunodeficiency Virus (HIV) infection and/or active Hepatitis B (HBV) or
Hepatitis C (HCV) infection.
- 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 21 days after the last dose of trial treatment.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression free rate after 3 months of treatment |
Time Frame: | 3 months |
Safety Issue: | |
Description: | The proportion of patients with a complete response (CR), a partial response (PR) or a stable disease (SD) at 3 months. |
Secondary Outcome Measures
Measure: | Objective response rate after 3 months of treatment |
Time Frame: | 3 months |
Safety Issue: | |
Description: | The proportion of patients with a complete or a partial response (CR or PR) as best overall response at 3 months. |
Measure: | Duration of Response |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | 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. |
Measure: | Progression Free Survival |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | 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 |
Measure: | Overall survival |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | The time from the date of the first study drug administration to the date of death due to any cause |
Measure: | Percentage of long-term responders (> 6 months) |
Time Frame: | 6 months |
Safety Issue: | |
Description: | The proportion of long term responders (> 6 months) |
Measure: | Adverse Events |
Time Frame: | Up to 3 years |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Centre Leon Berard |
Trial Keywords
- Metastatic Solid Neoplasm
- Advanced Solid Tumor
- Genomic alteration
- Targeted therapy
- Cabozantinib
- Ribociclib
- HDM201
- Alectinib
Last Updated
July 28, 2021