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

NCT ID: NCT03911193

Last Updated: 2019-04-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-21

Study Completion Date

2020-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Non-Small Cell Lung Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cabozantinib

Intervention Type DRUG

Patients will be treated with cabozantinib 60 mg/daily (cycles each 28 days) until progression, toxicity or patient refusal.

Interventions

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Cabozantinib

Patients will be treated with cabozantinib 60 mg/daily (cycles each 28 days) until progression, toxicity or patient refusal.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione Ricerca Traslazionale

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Federico Cappuzzo

Role: PRINCIPAL_INVESTIGATOR

AUSL Romagna- P.O. di Ravenna

Locations

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A.O. "S.Giuseppe Moscati"

Avellino, AV, Italy

Site Status NOT_YET_RECRUITING

IRCCS Oncologico Giovanni Paolo II

Bari, BA, Italy

Site Status ACTIVE_NOT_RECRUITING

A.O.U. Careggi

Florence, FI, Italy

Site Status NOT_YET_RECRUITING

Irccs Irst

Meldola, FO, Italy

Site Status ACTIVE_NOT_RECRUITING

Ospedale Infermi Rimini

Rimini, FO, Italy

Site Status ACTIVE_NOT_RECRUITING

A.O. Papardo

Messina, ME, Italy

Site Status NOT_YET_RECRUITING

Istituto Europeo di Oncologia

Milan, MI, Italy

Site Status ACTIVE_NOT_RECRUITING

Ospedale San Gerardo

Monza, MI, Italy

Site Status NOT_YET_RECRUITING

AOU Policlinico di Modena

Modena, MO, Italy

Site Status NOT_YET_RECRUITING

Casa di Cura La Maddalena

Palermo, PA, Italy

Site Status NOT_YET_RECRUITING

Istituto Oncologico Veneto

Padua, PD, Italy

Site Status NOT_YET_RECRUITING

A.O. S.M. Misericordia

Perugia, PG, Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, PI, Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliero- Universitaria di Parma

Parma, PR, Italy

Site Status NOT_YET_RECRUITING

AUSL Reggio Emilia- IRCCS Arcispedale S.M. Nuova

Reggio Emilia, RE, Italy

Site Status ACTIVE_NOT_RECRUITING

Fondazione Policlinico Gemelli

Roma, RM, Italy

Site Status NOT_YET_RECRUITING

Istituto Nazionale Tumori Regina Elena

Roma, RO, Italy

Site Status ACTIVE_NOT_RECRUITING

A.O.U. S. Luigi Gonzaga

Orbassano, Torino, Italy

Site Status NOT_YET_RECRUITING

AUSL della Romagna

Ravenna, , Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Integrata di Verona

Verona, , Italy

Site Status ACTIVE_NOT_RECRUITING

Countries

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Italy

Central Contacts

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Federico Cappuzzo

Role: CONTACT

0544285206

Lorenza Landi

Role: CONTACT

Facility Contacts

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Cesare Gridelli

Role: primary

0825-203945

Francesco Di Costanzo

Role: primary

055-7947298

Vincenzo Adamo

Role: primary

090-3996150

Diego Cortinovis

Role: primary

039-2339678

Fausto Barbieri

Role: primary

Vittorio Gebbia

Role: primary

Laura Bonanno

Role: primary

Fausto Roila

Role: primary

075-5784211

Antonio Chella

Role: primary

050-996653

Marcello Tiseo

Role: primary

0521-702316

Emilio Bria

Role: primary

Silvia Novello

Role: primary

011-9026978

Federico Cappuzzo

Role: primary

0544285206

Other Identifiers

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CABinMET

Identifier Type: -

Identifier Source: org_study_id

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