CABozantinib in Non-Small Cell Lung Cancer (NSCLC) Patients With MET Deregulation (CABinMET)

April 8, 2019 updated by: Fondazione Ricerca Traslazionale

Phase II Single Arm Study With CABozantinib in Non-Small Cell Lung Cancer Patients With MET Deregulation

This is a multicenter, single arm, phase II study evaluating efficacy in terms of RR in a cohort of NSCLC with MET amplification or MET exon 14 skipping mutation pre-treated or not with MET inhibitors.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study population will include NSCLC patients with MET amplification or MET exon 14 skipping mutation pre-treated or not with MET inhibitors. Elegible NSCLC patients with MET exon 14 skipping mutations or MET amplification will be treated with open label orally cabozantinib 60 mg/daily, cycles each 28 days. Disease evaluation will be performed every two months (8 weeks). Patients will be treated with cabozantinib until disease progression, unacceptable toxicity or patient refusal.Treatment will be continued until disease progression, unacceptable toxicity or patient refusal. Treatment beyond disease progression is allowed if considered appropriate by the investigator.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Italy
      • Ravenna, Italy
      • Verona, Italy, 37134
        • Active, not recruiting
        • Azienda Ospedaliero Universitaria Integrata di Verona
    • AV
      • Avellino, AV, Italy, 83100
        • Not yet recruiting
        • A.O. "S.Giuseppe Moscati"
        • Contact:
    • BA
      • Bari, BA, Italy, 70124
        • Active, not recruiting
        • IRCCS Oncologico Giovanni Paolo II
    • FI
      • Firenze, FI, Italy, 50134
    • FO
      • Meldola, FO, Italy, 47014
        • Active, not recruiting
        • Irccs Irst
      • Rimini, FO, Italy, 47923
        • Active, not recruiting
        • Ospedale Infermi Rimini
    • ME
      • Messina, ME, Italy, 98158
        • Not yet recruiting
        • A.O. Papardo
        • Contact:
    • MI
      • Milano, MI, Italy, 20141
        • Active, not recruiting
        • Istituto Europeo di Oncologia
      • Monza, MI, Italy, 20900
    • MO
    • PA
      • Palermo, PA, Italy, 90146
    • PD
    • PG
      • Perugia, PG, Italy, 06129
        • Not yet recruiting
        • A.O. S.M. Misericordia
        • Contact:
    • PI
      • Pisa, PI, Italy, 56124
        • Not yet recruiting
        • Azienda Ospedaliero Universitaria Pisana
        • Contact:
    • PR
      • Parma, PR, Italy, 43126
        • Not yet recruiting
        • Azienda Ospedaliero- Universitaria di Parma
        • Contact:
    • RE
      • Reggio Emilia, RE, Italy, 42123
        • Active, not recruiting
        • AUSL Reggio Emilia- IRCCS Arcispedale S.M. Nuova
    • RM
    • RO
      • Roma, RO, Italy, 00144
        • Active, not recruiting
        • Istituto Nazionale Tumori Regina Elena
    • Torino
      • Orbassano, Torino, Italy, 10043
        • Not yet recruiting
        • A.O.U. S. Luigi Gonzaga
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 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 cf-DNA at the local lab or in the central 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:

    1. ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support
    2. Platelet count ≥ 100,000/μL without transfusion
    3. Hemoglobin ≥ 9.0 g/dL Patients may be transfused to meet this criterion

    4. 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.
    5. Serum bilirubin ≤ 1.25 × ULN
    6. Patients with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may be enrolled
    7. 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:

  1. Tissue sample not available in patients without MET exon 14 skipping mutation detected in cf-DNA
  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 cardio-vascular 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cabozantinib
Elegible NSCLC patients with MET exon 14 skipping mutations or MET amplification will be treated with open label orally cabozantinib 60 mg/daily, cycles each 28 days.
Drug: Cabozantinib
Patients will be treated with cabozantinib 60 mg/daily (cycles each 28 days) until progression, toxicity or patient refusal.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Response Rate (RR) (complete + partial responses)
Time Frame: Up to 36 months
RR will be evaluated by investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Partial and complete responses will be confirmed following RECIST criteria 1.1. Disease evaluation will be performed every two months (8 weeks).
Up to 36 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS)
Time Frame: Up to 36 months
Disease evaluation will be performed every 8 weeks
Up to 36 months
Overall survival (OS)
Time Frame: Up to 36 months
Disease evaluation will be performed every 8 weeks
Up to 36 months
Disease Control Rate (DCR: stable disease + partial response + complete response)
Time Frame: Up to 36 months
Disease evaluation will be performed every 8 weeks
Up to 36 months
Exploratory biomarkers
Time Frame: Up to 36 months
At baseline, at the first disease evaluation and at progression of disease a blood sample will be collected for biomarkers analyses
Up to 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione Ricerca Traslazionale

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Federico Cappuzzo, AUSL Romagna- P.O. di Ravenna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 21, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2020

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 28, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 11, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 11, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 8, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CABinMET

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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