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

Non-Small Cell Lung Cancer Clinical Trial

— CABinMET  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03911193
• Other study ID #: CABinMET
• Status: Recruiting
• Phase: Phase 2
• Start date: September 21, 2018
• Est. completion date: September 2020

Study information

• Verified date: March 2019
• Source: Fondazione Ricerca Traslazionale
• Contact: Federico Cappuzzo
• Phone: 0544285206
• Email: f.cappuzzo[@]googlemail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: September 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
Italy	A.O. "S.Giuseppe Moscati"	Avellino	AV
Italy	IRCCS Oncologico Giovanni Paolo II	Bari	BA
Italy	A.O.U. Careggi	Firenze	FI
Italy	Irccs Irst	Meldola	FO
Italy	A.O. Papardo	Messina	ME
Italy	Istituto Europeo di Oncologia	Milano	MI
Italy	AOU Policlinico di Modena	Modena	MO
Italy	Ospedale San Gerardo	Monza	MI
Italy	A.O.U. S. Luigi Gonzaga	Orbassano	Torino
Italy	Istituto Oncologico Veneto	Padova	PD
Italy	Casa di Cura La Maddalena	Palermo	PA
Italy	Azienda Ospedaliero- Universitaria di Parma	Parma	PR
Italy	A.O. S.M. Misericordia	Perugia	PG
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	PI
Italy	AUSL della Romagna	Ravenna
Italy	AUSL Reggio Emilia- IRCCS Arcispedale S.M. Nuova	Reggio Emilia	RE
Italy	Ospedale Infermi Rimini	Rimini	FO
Italy	Fondazione Policlinico Gemelli	Roma	RM
Italy	Istituto Nazionale Tumori Regina Elena	Roma	RO
Italy	Azienda Ospedaliero Universitaria Integrata di Verona	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Ricerca Traslazionale

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression free survival (PFS)	Disease evaluation will be performed every 8 weeks	Up to 36 months
Secondary	Overall survival (OS)	Disease evaluation will be performed every 8 weeks	Up to 36 months
Secondary	Disease Control Rate (DCR: stable disease + partial response + complete response)	Disease evaluation will be performed every 8 weeks	Up to 36 months
Secondary	Exploratory biomarkers	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