all histological types of advanced / metastatic tumors with alterations molecular identified
Conditions
Interventions
Product Name: HDM201
Pharmaceutical Form: Capsule, hard
Trade Name: Kisqali
Product Name: Ribociclib
Pharmaceutical Form: Coated tablet
Trade Name: Cabometyx
Product Name: Cabozantinib
Pharmaceutica
Sponsors
Centre Léon Bérard
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General criteria: - Male or female patients aged of at least 18 years on day of signing informed consent. - Patients with histologically confirmed diagnosis of metastatic or locally advanced solids tumors. - A multidisciplinary molecular board must have recommended the specific MTT based on the following documented actionable alterations: Cohorte Ribociclib + HDM201 = 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. Cohorte 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. - 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, as per laboratory tests performed within 7 days prior to C1D1 (see specific criteria in protocole for each cohort) - Specific toxicities related to any prior anti-cancer therapy must have resolved to grade =1 (according to NCI CTCAE v5.0), except for alopecia (all grades), grade 2 neuropathy or anemia. - Women of child-bearing potential must have a negative serum pregnancy test within 7 days of first dose of study drugs and agree to use effective contraception from the date of negative pregnancy test and after the last dose of study drugs (see each specific cohort for the duration) - Fertile men must agree to use effective contraception from C1D1 and after the last dose of study drugs (see each specific cohort for the duration). - 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: General 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 with known hypersensitivity to excipients of products - 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. - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the activity of selected study drugs for each cohort based on molecular alterations /characteristics of patient’s tumor ;Secondary Objective: - To further document the clinical activity of study drugs for each cohort (Objective response rate after 3 months of treatment (3M-ORR); Duration of Response (DoR);Progression Free Survival (PFS); Overall survival (OS);Percentage of long-term responders (> 6 months)) - To assess the safety profile of the study drugs for each cohort. - Exploratory objective: follow the evolution of the mutations identified in ctDNA and to evaluate the correlation with efficacy endpoints.;Primary end point(s): Progression free rate after 3 months of treatment (3M-PFR).;Timepoint(s) of evaluation of this end point: after 3 months of treatment (3M-PFR). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Objective response rate after 3 months of treatment (3M-ORR) - Duration of Response (DoR) - Progression Free Survival (PFS) - Overall survival (OS) - Percentage of long-term responders (> 6 months) - 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. - Compare the type of mutations identified before and after study drug initiation and to evaluate the correlation with efficacy endpoints. ;Timepoint(s) of evaluation of this end point: Objective response rate : after 3 month of treatment Others points : up to 1 year of follow-up | — |
Countries
France
Contacts
Public ContactDRCI
Centre Léon Bérard
Outcome results
None listed