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

NCT03911193 | Unknown Phase 2

• 1 other identifier: CABinMET
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 20

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Response Rate (RR) (complete + partial responses)

  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 Outcomes (4)

• Progression free survival (PFS)

  Up to 36 months

• Overall survival (OS)

  Up to 36 months

• Disease Control Rate (DCR: stable disease + partial response + complete response)

  Up to 36 months

• Exploratory biomarkers

  Up to 36 months

Study Arms (1)

Cabozantinib

EXPERIMENTAL

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

Interventions

Cabozantinib DRUG

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

Cabozantinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• 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.
• Measurable disease according to RECIST criteria version 1.1
• At least 1 prior line of standard therapy (chemotherapy and/ or immunotherapy)
• Performance status 0-1 (ECOG)
• Age ≥18 years
• 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
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to enrollment:
• ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support
• Platelet count ≥ 100,000/μL without transfusion
• Hemoglobin ≥ 9.0 g/dL Patients may be transfused to meet this criterion
• 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.

You may not qualify if:

• Tissue sample not available in patients without MET exon 14 skipping mutation detected in cf-DNA
• No possibility to assess MET status
• Absence of any measurable disease according to RECIST criteria
• Co-existence of driver events, including EGFR mutations, KRAS mutations, ALK rearrangements or ROS-1 rearrangements
• No prior therapy
• Concomitant chemotherapy or immunotherapy or radiotherapy
• Symptomatic brain metastasis
• Uncontrolled significant inter-current or recent illness, including cardio-vascular disorders and gastro-intestinal disorders
• Major surgery within 2 months before first dose of study treatment
• Concomitant anti-coagulation with oral anti-coagulants or plated inhibitors
• 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
• 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)
• Pregnancy or breastfeeding

Sponsors & Collaborators

• Fondazione Ricerca Traslazionale: lead

Study Sites (20)

A.O. "S.Giuseppe Moscati"

Avellino, AV, 83100, Italy

NOT YET RECRUITING

IRCCS Oncologico Giovanni Paolo II

Bari, BA, 70124, Italy

ACTIVE NOT RECRUITING

A.O.U. Careggi

Florence, FI, 50134, Italy

NOT YET RECRUITING

Irccs Irst

Meldola, FO, 47014, Italy

ACTIVE NOT RECRUITING

Ospedale Infermi Rimini

Rimini, FO, 47923, Italy

ACTIVE NOT RECRUITING

A.O. Papardo

Messina, ME, 98158, Italy

NOT YET RECRUITING

Istituto Europeo di Oncologia

Milan, MI, 20141, Italy

ACTIVE NOT RECRUITING

Ospedale San Gerardo

Monza, MI, 20900, Italy

NOT YET RECRUITING

AOU Policlinico di Modena

Modena, MO, 41124, Italy

NOT YET RECRUITING

Casa di Cura La Maddalena

Palermo, PA, 90146, Italy

NOT YET RECRUITING

Istituto Oncologico Veneto

Padua, PD, 35128, Italy

NOT YET RECRUITING

A.O. S.M. Misericordia

Perugia, PG, 06129, Italy

NOT YET RECRUITING

Azienda Ospedaliero Universitaria Pisana

Pisa, PI, 56124, Italy

NOT YET RECRUITING

Azienda Ospedaliero- Universitaria di Parma

Parma, PR, 43126, Italy

NOT YET RECRUITING

AUSL Reggio Emilia- IRCCS Arcispedale S.M. Nuova

Reggio Emilia, RE, 42123, Italy

ACTIVE NOT RECRUITING

Fondazione Policlinico Gemelli

Roma, RM, 00168, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori Regina Elena

Roma, RO, 00144, Italy

ACTIVE NOT RECRUITING

A.O.U. S. Luigi Gonzaga

Orbassano, Torino, 10043, Italy

NOT YET RECRUITING

AUSL della Romagna

Ravenna, Italy

RECRUITING

Azienda Ospedaliero Universitaria Integrata di Verona

Verona, 37134, Italy

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Federico Cappuzzo

  AUSL Romagna- P.O. di Ravenna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federico Cappuzzo

CONTACT

0544285206; f.cappuzzo@googlemail.com

Lorenza Landi

CONTACT

landi.lorenza@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: April 11, 2019
• Study Start: September 21, 2018
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: April 11, 2019

Record last verified: 2019-03

Locations

IT (20)