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

• Sponsor: Fondazione Ricerca Traslazionale (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT03911193
• Collaborator: (none)
• Enrollment: 25
• Locations: 20
• Arm: 1
• Anticipated Duration (Months): 23.4
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: Cabozantinib	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Single Arm Study With CABozantinib in Non-Small Cell Lung Cancer Patients With MET Deregulation
• Actual Study Start Date: Sep 21, 2018
• Anticipated Primary Completion Date: Sep 1, 2020
• Anticipated Study Completion Date: Sep 1, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Response Rate (RR) (complete + partial responses) [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).

Secondary Outcome Measures

1. Progression free survival (PFS) [Up to 36 months]

   Disease evaluation will be performed every 8 weeks

2. Overall survival (OS) [Up to 36 months]

   Disease evaluation will be performed every 8 weeks

3. Disease Control Rate (DCR: stable disease + partial response + complete response) [Up to 36 months]

   Disease evaluation will be performed every 8 weeks

4. Exploratory biomarkers [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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

10. ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support

11. Platelet count ≥ 100,000/μL without transfusion

12. Hemoglobin ≥ 9.0 g/dL Patients may be transfused to meet this criterion

13. 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.

1. Serum bilirubin ≤ 1.25 × ULN

2. Patients with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may be enrolled

3. Calculated creatinine clearance (CRCL) ≥ 45 mL/min or calculated CRCL must be ≥ 60 mL/min

4. Patient compliance to the study procedure

5. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	A.O. "S.Giuseppe Moscati"	Avellino	AV	Italy	83100
2	IRCCS Oncologico Giovanni Paolo II	Bari	BA	Italy	70124
3	A.O.U. Careggi	Firenze	FI	Italy	50134
4	Irccs Irst	Meldola	FO	Italy	47014
5	Ospedale Infermi Rimini	Rimini	FO	Italy	47923
6	A.O. Papardo	Messina	ME	Italy	98158
7	Istituto Europeo di Oncologia	Milano	MI	Italy	20141
8	Ospedale San Gerardo	Monza	MI	Italy	20900
9	AOU Policlinico di Modena	Modena	MO	Italy	41124
10	Casa di Cura La Maddalena	Palermo	PA	Italy	90146
11	Istituto Oncologico Veneto	Padova	PD	Italy	35128
12	A.O. S.M. Misericordia	Perugia	PG	Italy	06129
13	Azienda Ospedaliero Universitaria Pisana	Pisa	PI	Italy	56124
14	Azienda Ospedaliero- Universitaria di Parma	Parma	PR	Italy	43126
15	AUSL Reggio Emilia- IRCCS Arcispedale S.M. Nuova	Reggio Emilia	RE	Italy	42123
16	Fondazione Policlinico Gemelli	Roma	RM	Italy	00168
17	Istituto Nazionale Tumori Regina Elena	Roma	RO	Italy	00144
18	A.O.U. S. Luigi Gonzaga	Orbassano	Torino	Italy	10043
19	AUSL della Romagna	Ravenna		Italy
20	Azienda Ospedaliero Universitaria Integrata di Verona	Verona		Italy	37134

Sponsors and Collaborators

• Fondazione Ricerca Traslazionale

Investigators

• Principal Investigator: Federico Cappuzzo, AUSL Romagna- P.O. di Ravenna

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fondazione Ricerca Traslazionale
• ClinicalTrials.gov Identifier: NCT03911193
• Other Study ID Numbers: CABinMET
• First Posted: Apr 11, 2019
• Last Update Posted: Apr 11, 2019
• Last Verified: Mar 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Study Results

No Results Posted as of Apr 11, 2019