TIvantinib as Maintenance Treatment in Extended Small-cell Lung Cancer (TIMES)

Study Overview
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Brief Summary
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This study aims to assess the role of MET inhibitors as maintenance treatment in adult patients with extensive stage small cell lung cancer.

Official Title
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TIvantinib as Maintenance Treatment in Extended Small-cell Lung Cancer (TIMES). Phase II Clinical Trial, Single Arm, Two Stage

Conditions
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Carcinoma, Small Cell

Intervention / Treatment
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* Drug: ARQ197


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed extensive-stage SCLC Disease control after the first line platinum/etoposide treatment ECOG performance status of 0 or 1 Measurable disease according to RECIST Version 1.1 criteria Adequate bone marrow, liver, and renal function. Formalin Fixed Paraffin Embedded (FFPE) or frozen tumor tissue material must be available. Resolution of any toxic effects of prior therapy according to NCI CTCAE, v 4.0 Full recovery from significant complications of the surgery If childbearing age, use of double-barrier contraceptive measures, oral or abstaining from sexual intercourse during the study and up to 90 days after the last dose of chemotherapy Negative pregnancy test within 72 hours prior to the initiation of study treatment, if of childbearing potential Signed informed consent prior to beginning protocol specific procedures Patients must be available for treatment and follow-up Exclusion Criteria: Previous therapies with Tivantinib or other known c-MET inhibitor Radiotherapy for target lesions and major surgical procedure within 4 weeks, prior to the inclusion in the study Palliative radiotherapy within 2 weeks prior to the inclusion in the study History of malignancy in the past five years, excluding basal cell the cervix, prostate cancer with a value of prostate-specific antigen <0.2 ng / mL History of cardiac disease Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infections Pregnant or lactating women or childbearing/reproductive potential not using adequate contraception Need for breastfeeding during or within 12 weeks of completion of the study Gastrointestinal disorders that may interfere with the absorption of Tivantinib Inability or unwillingness to swallow the complete doses of Tivantinib Any known contraindication to treatment and other significant comorbid conditions which could jeopardize participation in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARQ-197<br>ARQ-197 360 mg twice/day by mouth (PO), with meals, continuously as maintenance treatment until disease progression or unacceptable toxicity. | Drug: ARQ197<br> <br> * Other names: Tivantinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | PFS will be assessed From the date of enrollment to the date of first documented disease progression or to the date of death from any cause or to the date of a new anti-cancer therapy, whichever occurs first. Patients without a PFS event at the time of analysis will be censored at the date of last assessment. | Approximately 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The survival status will be assessed every 12 weeks (±14 days) until 48 months. Patients alive at the time of analysis will be censored at the date of last assessment. | Approximately 48 months | 
| Disease control rate (DCR) | The DCR will be defined as the percentage of patients with complete response (CR), partial response (PR) and stable disease (SD) at enrollment until the final visit | Approximately 48 months | 
| Occurrence of all grade toxicity events assessed by CTCAE v4.0 | Toxicity will be analyzed in an as treated population, provided patients had received at least one dose of therapy. | Toxicity will be recorded during the treatment, until 30 days after the last dose of study medication, and graded according to the NCI- Common Terminology Criteria for Adverse Events (CTCAE) v.4. | 
| Quality of Life | The instruments used for assessing the quality of life are the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Quality of Life will be assessed from the date of enrollment until the end of treatment visit, that is anticipated after maximum 48 months. | Approximately 48 months |