Clinical trial NCT03911193: CABozantinib in Non-Small Cell Lung Cancer (NSCLC) Patients With MET Deregulation
Official title: Phase II Single Arm Study With CABozantinib in Non-Small Cell Lung Cancer Patients With MET Deregulation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Fondazione Ricerca Traslazionale
Sponsor class: OTHER
First posted: 2019-04-11
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Response Rate (RR) (complete + partial responses)
timeFrame: Up to 36 months
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: Up to 36 months
measure: Overall survival (OS)
timeFrame: Up to 36 months
measure: Disease Control Rate (DCR: stable disease + partial response + complete response)
timeFrame: Up to 36 months
measure: Exploratory biomarkers
timeFrame: Up to 36 months
Other outcomes:
Locations:
city: Avellino
country: Italy
facility: A.O. "S.Giuseppe Moscati"
state: AV
city: Bari
country: Italy
facility: IRCCS Oncologico Giovanni Paolo II
state: BA
city: Firenze
country: Italy
facility: A.O.U. Careggi
state: FI
city: Meldola
country: Italy
facility: Irccs Irst
state: FO
city: Rimini
country: Italy
facility: Ospedale Infermi Rimini
state: FO
city: Messina
country: Italy
facility: A.O. Papardo
state: ME
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: MI
city: Monza
country: Italy
facility: Ospedale San Gerardo
state: MI
city: Modena
country: Italy
facility: AOU Policlinico di Modena
state: MO
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena
state: PA
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
state: PD
city: Perugia
country: Italy
facility: A.O. S.M. Misericordia
state: PG
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: PI
city: Parma
country: Italy
facility: Azienda Ospedaliero- Universitaria di Parma
state: PR
city: Reggio Emilia
country: Italy
facility: AUSL Reggio Emilia- IRCCS Arcispedale S.M. Nuova
state: RE
city: Roma
country: Italy
facility: Fondazione Policlinico Gemelli
state: RM
city: Roma
country: Italy
facility: Istituto Nazionale Tumori Regina Elena
state: RO
city: Orbassano
country: Italy
facility: A.O.U. S. Luigi Gonzaga
state: Torino
city: Ravenna
country: Italy
facility: AUSL della Romagna
city: Verona
country: Italy
facility: Azienda Ospedaliero Universitaria Integrata di Verona
Study officials:
affiliation: AUSL Romagna- P.O. di Ravenna
name: Federico Cappuzzo
role: PRINCIPAL_INVESTIGATOR
References: