Trial Title:
Phase II Efficacy Study of Repotrectinib in Frail and/or Elderly Patients With ROS1-rearranged Advanced NSCLC
NCT ID:
NCT06552234
Condition:
NSCLC Stage IV
NSCLC, Stage III
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Conditions: Keywords:
tyrosine-kinase inhibitors
Frail patients
Elderly patients
ROS1 rearrangements
resistance
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Repotrectinib
Description:
Repotrectinib 160 mg BID, until progression or unacceptable toxicity
Arm group label:
Repotrectinib treatment
Summary:
ROS1 rearrangements are rare, accounting for only 1-2% of NSCLC cases, but have been
associated with response to ROS1 inhibitors, such as crizotinib and entrectinib. However,
many patients develop resistance to the tyrosine-kinase inhibitors (TKIs), creating a
need for new treatments.
Repotrectinib is a new-generation TKI designed against ROS1 or NTRK rearranged
malignancies (Drilon 2018). Early phase clinical data support activity of repotrectinib
in patients with NSCLC harboring such gene rearrangements (TRIDENT-1 study), but there
are limited evidence in frail populations, such as poor performance status patients
and/or elderly patients, who are classically excluded from clinical trials or
underrepresented.
The present study aims to assess the activity and tolerability of repotrectinib in frail
(PS ≥2) and/or elderly patients with ROS1-rearranged advanced NSCLC.
Detailed description:
This is a national, multicenter, phase II, prospective, open label, non-randomized,
interventional study.
Frail (PS≥2) and/or elderly patients (≥70 years) with histologically/cytologically proven
stage IV or stage III non-eligible to local treatment NSCLC harboring an ROS1 gene
rearrangement treated by Repotrectinib (160 mg twice a day (BID), until progression or
unacceptable toxicity) in first or any line.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Eligible patients are defined as patients with
- Eastern Cooperative Oncology Group (ECOG) PS ≥ 2 at the time of inclusion
and/or
- Age ≥ 70 years
- Age ≥ 18 years
- Histologically or cytologically confirmed diagnosis of locally advanced or
metastatic NSCLC harboring an ROS1 gene rearrangement as by any nucleic acid-based
diagnostic testing method (e.g., next-generation sequencing [NGS], Sanger
sequencing, reverse transcription-polymerase chain reaction), Break-apart
fluorescence in situ hybridization (FISH) or Immunohistochemistry (IHC) (confirmed
by NGS or qPCR test).
- Willing and able to provide written institutional review board (IRB)/institutional
ethics committee-approved Informed Consent.
- At least 1 measurable target lesion according to RECIST (v1.1). CNS-only measurable
disease as defined by RECIST (v1.1) is allowed.
- Prior cytotoxic chemotherapy for advanced or metastatic disease is allowed. At the
time of starting treatment with repotrectinib, at least 14 days or 5 half-lives
(whichever is shorter) must have elapsed after discontinuation of prior cytotoxic
chemotherapy (or at least 42 days for prior nitrosoureas, mitomycin C, and liposomal
doxorubicin) and all side effects from prior treatments must have resolved to grade
≤ _1 (CTCAE Version 5.0 with the exception of alopecia.
- Prior immunotherapy (e.g., anti-PD-1, anti-PDL1, anti-TIM3, anti-OX40) is allowed.
At the time of starting treatment with repotrectinib, at least 14 days must have
elapsed after discontinuation of prior immunotherapy treatment and all
immune-related side effects from prior treatments must have resolved to grade ≤ _1.
- No prior ROS1 TKI is allowed for the TKI naïve cohort.
- Prior ROS1 TKI is allowed for the TKI pretreated cohort (max 30% of patients). At
least 7 days or 5 half-lives (whichever is shorter) must have elapsed since
completion of treatment with the last ROS1i prior to starting treatment with
repotrectinib for subjects enrolling into the TKI-pretreated expansion cohorts. All
side effects from prior treatments with ROS1i must have resolved to grade ≤ _1 prior
to starting treatment with repotrectinib.
- Prior ROS1i allowed include crizotinib, ceritinib, lorlatinib, brigatinib,
entrectinib, ensartinib, cabozantinib.
- Subjects with symptomatic CNS metastases and/or asymptomatic leptomeningeal
carcinomatosis are eligible.
- Life expectancy ≥3 months
- Subject affiliated to an appropriate social security system
- Adequate hematologic and end-organ function, defined by the following laboratory
- ANC ≥ 1500 /mm3 without granulocyte colony-stimulating factor support
- Lymphocyte count ≥ 500/mm3
- Platelet count ≥ 100,000/mm3 without transfusion
- Hemoglobin ≥ 9.0 g/dL. Patients may be transfused to meet this criterion.
- INR or aPTT ≤ 1.5, upper limit of normal (ULN)
- This applies only to patients who are not receiving therapeutic
anticoagulation; patients receiving therapeutic anticoagulation should be
receiving a stable dose.
- ASAT, ALAT, and alkaline phosphatase ≤ 2.5xULN, with the following exceptions:
- Patients with documented liver metastases: ASAT and/or ALAT ≤ 5xULN
- Patients with documented liver or bone metastases: alkaline phosphatase < 5xULN
- Serum bilirubin ≤1.25xULN
- Patients with known Gilbert disease who have serum bilirubin level ≤ 3xULN may
be enrolled.
- Calculated creatinine clearance (CRCL) ≥ 45 mL/min
- Adequate method of contraception during the treatment period
- For Females:
All women of childbearing potential (WOCBP) must agree to avoid pregnancy during the
study and must use a highly effective method of contraception during study treatment with
repotrectinib and for at least 2 months following the final dose.
Highly effective contraceptive methods consist of prior sterilization, intrauterine
device (IUD), intrauterine hormone-releasing system (IUS), injectable or implantable
contraceptives and abstinence.
Hormonal contraception must begin 7 days prior to the first dose of study treatment.
Due to a potential loss of effectiveness of hormonal contraceptives caused by interaction
with study intervention, if WOCBP use hormonal contraceptives (including oral hormonal
contraceptives), they must use either another form of non-hormonal highly effective
contraception or a reliable barrier method.
Female subjects must refrain from egg donation from screening through at least 2 months
after the last dose of study drug.
- For Males:
Male participants with WOCBP partners must use latex condoms during treatment with
repotrectinib and for 4 months following the final dose even if the participant has
undergone a successful vasectomy or if the partner is pregnant or breastfeeding.
Male subjects must refrain from sperm donation from screening through at least 4 months
after the last dose of study drug
Exclusion Criteria:
- Malignancies other than NSCLC within 2 years prior to inclusion, with the exception
of those with a negligible risk of metastasis or death (e.g., expected 5-year OS ≥
90%) treated with expected curative outcome (such as adequately treated carcinoma in
situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer
treated surgically with curative intent, ductal carcinoma in situ treated surgically
with curative intent)
- Patients with active hepatitis B (chronic or acute; defined as having a positive
hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with
past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the
presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible
only if they are negative for HBV DNA. Patients positive for hepatitis C virus (HCV)
antibody are eligible only if PCR is negative for HCV RNA.
- Active tuberculosis
- Severe infections within 2 weeks prior to inclusion, including, but not limited to,
hospitalization for complications of infection, bacteremia, or severe pneumonia
- Significant cardiovascular disease, such as New York Heart Association cardiac
disease (Class II or greater), myocardial infarction, or cerebrovascular accident
within 3 months prior to inclusion, unstable arrhythmias, or unstable angina
- Major surgical procedure other than for diagnosis within 28 days prior to inclusion
or anticipation of need for a major surgical procedure during the course of the
study
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or renders the patient at high risk from treatment
complications.
- Patients with illnesses or conditions that interfere with their capacity to
understand follow and/or comply with study procedures.
- Concurrent participation in any therapeutic clinical trial
- Patient deprived of liberty or placed under the authority of a tutor or a curator
- Assessed by the investigator to be unable or unwilling to comply with the
requirements of the protocol
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CH Aix-en-Provence
Address:
City:
Aix-en-Provence
Country:
France
Contact:
Last name:
Stéphanie MARTINEZ
Email:
smartinez@ch-aix.fr
Facility:
Name:
AP-HM
Address:
City:
Marseille
Country:
France
Facility:
Name:
HIA Sainte Anne
Address:
City:
Toulon
Country:
France
Contact:
Last name:
Olivier BYLICKI
Email:
bylicki.olivier@yahoo.fr
Facility:
Name:
CHU Angers
Address:
City:
Angers
Country:
France
Contact:
Last name:
Grégoire JUSTEAU
Email:
gregoire.justeau@chu-angers.fr
Facility:
Name:
CHU Bordeaux
Address:
City:
Bordeaux
Country:
France
Contact:
Last name:
Claire BARDEL
Email:
claire.bardel@chu-bordeaux.fr
Facility:
Name:
CHU Brest
Address:
City:
Brest
Country:
France
Contact:
Last name:
Margaux GEIER
Email:
margaux.geier@chu-brest.fr
Facility:
Name:
Centre François Baclesse
Address:
City:
Caen
Country:
France
Facility:
Name:
CH Chambéry
Address:
City:
Chambéry
Country:
France
Contact:
Last name:
Julian PINSOLLE
Email:
julian.pinsolle@ch-metropole-savoie.fr
Facility:
Name:
Hôpitaux civils de Colmar
Address:
City:
Colmar
Country:
France
Contact:
Last name:
Lionel MOREAU
Email:
lionel.moreau@ch-colmar.fr
Facility:
Name:
CHI Créteil
Address:
City:
Créteil
Country:
France
Contact:
Last name:
Gaëlle ROUSSEAU BUSSAC
Email:
gaelle.rousseaubussac@chicreteil.fr
Facility:
Name:
CHD Vendée
Address:
City:
La Roche-sur-Yon
Country:
France
Contact:
Last name:
Acya BIZIEUX
Email:
acya.bizieux@ght85.fr
Facility:
Name:
CHRU Lille
Address:
City:
Lille
Country:
France
Contact:
Last name:
Alexis CORTOT
Email:
alexis.cortot@chu-lille.fr
Facility:
Name:
CHU Limoges
Address:
City:
Limoges
Country:
France
Contact:
Last name:
Alain VERGNENEGRE
Email:
aalain.vergnenegre@unilim.fr
Facility:
Name:
Hospices Civils de Lyon
Address:
City:
Lyon
Country:
France
Contact:
Last name:
Thomas PIERRET
Email:
thomas.pierret@chu-lyon.fr
Facility:
Name:
CH Cornouaille
Address:
City:
Quimper
Country:
France
Contact:
Last name:
Maël DOMBLIDES
Email:
mael.domblides@ch-cornouaille.fr
Facility:
Name:
CHU Rennes
Address:
City:
Rennes
Country:
France
Contact:
Last name:
Yannick LE GUEN
Email:
yannick.le.guen@chu-rennes.fr
Facility:
Name:
CHU Rouen
Address:
City:
Rouen
Country:
France
Contact:
Last name:
Florian GUISIER
Email:
florian.guisier@chu-rouen.fr
Facility:
Name:
Hôpital Foch
Address:
City:
Suresnes
Country:
France
Contact:
Last name:
Hélène DOUBRE
Email:
h.doubre@hopital-foch.com
Facility:
Name:
CHU Toulouse
Address:
City:
Toulouse
Country:
France
Contact:
Last name:
Laurence BIGAY-GAME
Email:
bigaygame.l@chu-toulouse.fr
Facility:
Name:
Hôpitaux Nord-Ouest
Address:
City:
Villefranche-sur-Saône
Country:
France
Contact:
Last name:
Lionel FALCHERO
Email:
lfalchero@hno.fr
Start date:
October 2024
Completion date:
September 2031
Lead sponsor:
Agency:
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
Agency class:
Other
Collaborator:
Agency:
Groupe Français de Pneumo-Cancérologie
Agency class:
Other
Collaborator:
Agency:
Hospices Civils de Lyon
Agency class:
Other
Source:
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06552234
