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

Unknown

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

25

Phase

  • 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 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

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
Intervention / Treatment
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

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

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

Fondazione Ricerca Traslazionale

Investigators

  • 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)

September 21, 2018

Primary Completion (Anticipated)

September 1, 2020

Study Completion (Anticipated)

September 1, 2020

Study Registration Dates

First Submitted

March 28, 2019

First Submitted That Met QC Criteria

April 8, 2019

First Posted (Actual)

April 11, 2019

Study Record Updates

Last Update Posted (Actual)

April 11, 2019

Last Update Submitted That Met QC Criteria

April 8, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID 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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