Evaluation of Cabozantinib Efficacy in Non-Small Cell Lung Cancer Patients with MET Deregulation: A Phase II Single-Arm Study
- Trial ID
- 2024-518386-95-02
- Protocol
- CABinMET
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase II single-arm study is to evaluate the **efficacy** of Cabozantinib in patients with **Non-Small Cell Lung Cancer** (NSCLC) exhibiting MET amplification or MET exon 14 skipping mutation. The study aims to determine the response rate (RR) of Cabozantinib in these patients, whether they have been pretreated with MET inhibitors or not. This is clinically relevant as it seeks to establish the potential of Cabozantinib as a therapeutic option for a specific subset of NSCLC patients, potentially improving treatment outcomes for those with MET deregulation.
Participants
The clinical trial involves participants diagnosed with **non-small-cell lung cancer** (NSCLC), specifically those with MET amplification or MET exon 14 skipping mutation. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a performance status of 0-1 according to the Eastern Cooperative Oncology Group (ECOG) criteria, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not include a vulnerable population. Participants must have adequate hematologic and end organ function, as defined by specific laboratory criteria, and must comply with study procedures. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that participants have a measurable disease according to RECIST criteria version 1.1 and have undergone at least one prior line of standard therapy, which may include chemotherapy or immunotherapy. Lifestyle considerations such as diet and physical activity are not specified in the trial details.
Plans and Procedures
The clinical trial is a **Phase II** single-arm study designed to evaluate the efficacy of **cabozantinib** in patients with **non-small-cell lung cancer** (NSCLC) exhibiting MET deregulation. The primary objective is to assess the response rate (RR) in patients with MET amplification or MET exon 14 skipping mutation, whether pre-treated with MET inhibitors or not. The trial is expected to run from December 15, 2017, to July 31, 2025, with a maximum treatment period of 12 months for each participant. The study employs a non-randomized, open-label design, focusing on the administration of **CABOMETYX** film-coated tablets, available in 20 mg, 40 mg, and 60 mg dosages, taken orally.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histological diagnosis of NSCLC, presence of MET mutations, and adequate organ function. Following the screening, participants will receive the study medication and attend regular follow-up visits to monitor treatment response and safety. These visits will include assessments of disease progression, overall survival, and disease control rate, alongside exploratory biomarker analysis from blood and tissue samples. The end-of-study visit will conclude the participant's involvement, evaluating the overall treatment efficacy and safety profile.
Participant involvement is anticipated to last up to 12 months, contingent upon individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The trial's primary endpoint is the response rate, while secondary endpoints include progression-free survival, overall survival, and disease control rate. The study is not classified as low intervention, and it adheres to rigorous scientific and ethical standards to ensure the validity and reliability of the findings.
Treatment
The clinical trial involves the administration of **CABOMETYX** film-coated tablets, which contain the active substance **cabozantinib**. The trial includes three different dosages of CABOMETYX: 20 mg, 40 mg, and 60 mg. Each dosage is provided in the form of film-coated tablets, designed for **oral** administration. The maximum daily dose for the 20 mg and 60 mg tablets is 60 mg, while the 40 mg tablets have a maximum daily dose of 40 mg. The total maximum dose for all formulations is capped at 140 mg. The treatment period is set for a maximum of 12 months. The active substance, cabozantinib, is a chemical compound also known by its synonyms XL-184 and Cyclopropane-1,1-dicarboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide. The pharmaceutical product is manufactured by IPSEN PHARMA and is authorized for use in the European Union under the marketing authorization numbers EU/1/16/1136/002, EU/1/16/1136/004, and EU/1/16/1136/006 for the 20 mg, 40 mg, and 60 mg tablets, respectively.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is a single-arm study focusing on the efficacy of cabozantinib in patients with non-small cell lung cancer (NSCLC) exhibiting MET deregulation. The primary objective is to evaluate the response rate in patients with MET amplification or MET exon 14 skipping mutation, regardless of prior treatment with MET inhibitors. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.
Efficacy
The efficacy of **Cabozantinib** in the treatment of Non-Small Cell Lung Cancer (NSCLC) with MET deregulation will be assessed through a Phase II single-arm clinical trial. The primary endpoint for evaluating efficacy is the Response Rate (RR), which includes both complete and partial responses in patients with MET amplification or MET exon 14 skipping mutation, whether pre-treated with MET inhibitors or not. Secondary endpoints include Progression-Free Survival (PFS), Overall Survival (OS), and Disease Control Rate (DCR), which encompasses stable disease, partial response, and complete response. Additionally, exploratory biomarkers will be analyzed from blood and tissue samples, with optional tissue samples provided at disease progression.
Measurements of efficacy parameters will be conducted according to the RECIST criteria version 1.1 for assessing measurable disease. The trial will involve the collection and analysis of laboratory results to ensure adequate hematologic and end organ function, as defined by specific criteria such as ANC, platelet count, hemoglobin levels, and liver function tests. The trial is scheduled to conclude by July 31, 2025, with the recruitment having started on December 15, 2017. The maximum treatment period for participants is set at 12 months, with the administration of Cabozantinib in the form of film-coated tablets taken orally.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Citological or histological diagnosis of non-small-cell-lung cancer (NSCLC) stage III B (not suitable for local treatments with curative intent) or stage IV. 2. Tissue samples available for MET analysis (archivial tissue or tissue collected at study entry); patients without archival tumor tissue or refusing new biopsy at study entry, are eligible if MET mutation is detected in cf-DNA 3. Presence of MET mutations (exon 14 skipping mutation ONLY) detected in tissue or in cf-DNA detected at the local lab or MET amplification (MET/CEP7 ratio > 2.2) detected in the central lab ONLY. 4. Measurable disease according to RECIST criteria version 1.1 5. At least 1 prior line of standard therapy (chemotherapy and/ or immunotherapy) 6. Performance status 0-1 (ECOG) 7. Age ≥18 years 8. Patients potentially fertile using adequate methods of contraception in order to avoid childbearing. Contraceptive methods must be respected by male and female patients and their partners during study treatment period and at least 4 months after completing therapy 9. Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to enrollment: a. ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support b. Platelet count ≥ 100,000/μL without transfusion c. Hemoglobin ≥ 9.0 g/dL Patients may be transfused to meet this criterion d. AST, ALT, and alkaline phosphatase ≤ 2.5 × ULN, with the following exceptions: - Patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN - Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN. e. Serum bilirubin ≤ 1.25 × ULN f. Patients with known Gilbert disease who have serum bilirubin level ≤ 3 mg/dL may be enrolled g. Calculated creatinine clearance (CRCL) ≥ 45 mL/min or calculated CRCL must be ≥ 60 mL/min 10. Patient compliance to the study procedure 11. Written informed consent
Exclusion Criteria
- Tissue sample not available for the central assessing of MET amplification 2. No possibility to assess MET status 3. Absence of any measurable disease according to RECIST criteria 4. Co-existence of driver events, including EGFR mutations, KRAS mutations, ALK rearrangements or ROS-1 rearrangements 5. No prior therapy 6. Concomitant chemotherapy or immunotherapy or radiotherapy 7. Symptomatic brain metastasis 8. Uncontrolled significant inter-current or recent illness, including cardiovascular disorders and gastro-intestinal disorders 9. Major surgery within 2 months before first dose of study treatment 10. Concomitant anti-coagulation with oral anti-coagulants or plated inhibitors 11. History of significant bleeding, trachea-bronchial tree/major blood vessels invading tumors, cavity pulmonary lesions and GI disorders associated with a risk of perforation or fistula formation 12. Diagnosis of another cancer in the last 3 years, except for in situ carcinoma of cervix, breast and bladder or skin carcinoma (squamous or basalioid) 13. Pregnancy or breastfeeding
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Yet Recruiting | 15 Dec 2017 | 25 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
CABOMETYX 60 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 60 | 12 | PRD4382746 |
CABOMETYX 20 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 60 | 12 | PRD4381882 |
CABOMETYX 40 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 40 | 12 | PRD4382703 |