Clinical trial evaluating the value of treatment with therapy specifically targeting the molecular alterations identified in the tumor of patients with advanced or metastatic cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Leon Berard

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Jun 2020 → ongoing

Decision date (initial)

2024-09-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-510567-35-00

EudraCT number

2019-001494-88

ClinicalTrials.gov

NCT04116541

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the activity of selected study drugs for each cohort based on molecular alterations /characteristics of patient’s tumor

Secondary objectives 3

1. To further document the clinical activity of study drugs for each cohort (Objective response rate after 3 months of treatment (3M-ORR) (12 weeeks); Duration of Response (DoR); Progression Free Survival (PFS); Overall survival (OS); Percentage of long-term responders (> 6 months))
2. To assess the safety profile of the study drugs for each cohort
3. Exploratory objective: follow the evolution of the mutations identified in ctDNA and to evaluate the correlation with efficacy endpoints.

Conditions and MedDRA coding

Advanced / metastatic cancers

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. General criteria: - Male or female patients aged of at least 18 years on day of signing informed consent.
2. Patients with histologically confirmed diagnosis of metastatic disease or unresectable locally advanced malignancy (solid tumors) 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.
3. A multidisciplinary molecular board must have recommended the specific MTT based on the following documented actionable alterations:Cohort 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 (Closed). 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 (for instance R1275Q, F1245C, F1174X) , or activating rearrangements following validation by central molecular tumor board of Centre Léon Bérard. Cohort Regorafenib = 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 of RAF1 (Closed) Cohort Trametinib + Dabrafenib = BRAF V600 mutation and/ or rearrangement of BRAF following validation by central molecular tumor board of Centre Léon Bérard.
4. Previously treated by at least one prior line of treatment in the advanced/metastatic setting.
5. 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
6. 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.
7. Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
8. 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.
9. 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).
10. Unless documented infertility, men must agree to use effective contraception from C1D1 and after the last dose of study drugs (see each specific cohort for the duration).
11. 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.
12. Patient must be covered by a medical insurance.

Exclusion criteria 10

1. General criteria: Patients amenable to therapy with curative intent.
2. Patients participating to another clinical trial with a medicinal product.
3. Patients previously treated with similar MTT meaning any agent targeting the same signaling pathways components.
4. Patients with known hypersensitivity to excipients of products.
5. 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.
6. 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.
7. Known Human Immunodeficiency Virus (HIV) infection and/or active Hepatitis B (HBV) or Hepatitis C (HCV) infection.
8. 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.
9. Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
10. Patients who are pregnant or breastfeeding women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 5

1. Objective response rate after 3 months of treatment (3M-ORR)
2. Duration of Response (DoR)
3. Progression Free Survival (PFS)
4. Overall survival (OS)
5. Percentage of long-term responders (> 6 months)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Leon Berard

Sponsor organisation

Centre Leon Berard

Address

28 Rue Laennec

City

Lyon

Postcode

69008

Country

France

Scientific contact point

Organisation

Centre Leon Berard

Contact name

Jean-Yves BLAY

Public contact point

Organisation

Centre Leon Berard

Contact name

Project manager

Third parties 1

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 30 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications