Small Cell Lung Cancer (SCLC) after first-line platinum plus etoposide therapy MedDRA version: 17.0 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Tivantinib
Product Code: ARQ197
Pharmaceutical Form: Tablet
INN or Proposed INN: TIVANTINIB
CAS Number: 905854-02-6
Current Sponsor code: ARQ 197
Other descriptive name: (3R,4R)-3-(5,6-D
Sponsors
Istituto Oncologico del Veneto IRCCS – UOC Oncologia Medica 2
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age = 18 years. • 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 (including radiotherapy) according to NCI CTCAE, version 4.0, = Grade 1 (except for alopecia). • 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 33 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 33
Exclusion criteria
Exclusion criteria: • Clinically unstable central nervous system metastases • 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 carcinoma of the skin, adequately treated intraepithelial carcinoma of 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 co-morbid conditions which could jeopardize participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the impact of Tivantinib in increasing the progression free survival (PFS) in the intention to treat (ITT) population;Secondary Objective: To evaluate overall survival (OS), safety, disease control rate (DCR) in the ITT population. Additional exploratory objectives include evaluation of quality of life (QoL) in the ITT population, analysis of PFS and OS according to response to the first line treatment and in patients with MET amplification and MET and p-MET overexpression; evaluation of MET pathway dysregulation by analysis of mutations of the genes MET, PIK3CA, AKT, PTEN, RAS, RAF, and MEK; to evaluate acquisition of resistance and molecular changes.;Primary end point(s): Progression free survival, assessed from the date of enrolment to the date of disease progression or to the date of death, whichever occurs first ;Timepoint(s) of evaluation of this end point: The progression free survival (PFS) will be determined as the time from the date of enrolment to the date of disease progression (or relapse) or to the date of death, whichever occurs first. Patients without a PFS event at the time of analysis will be censored at the date of last assessment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival, assessed from the date of enrolment to the date of death from any cause • Disease control rate, as percentage of patients achieving a complete response plus partial response plus stable disease • Toxicity during the treatment, graded according to the NCI-Common Terminology Criteria for Adverse Events (CTCAE) v.4. • PFS and OS according to type of response to the first-line treatment • PFS, OS and DCR according to MET amplification and MET and p-MET overexpression, mutations of the genes MET, PIK3CA, AKT, PTEN, RAS, RAF, and MEK using next generation sequencing (NGS) at baseline and at the disease progression • Quality of Life assessed by EORTC QLQ-C30 and QLQ-LC13;Timepoint(s) of evaluation of this end point: - The OS will be determined as the time from the date of enrolment to the date of death from any cause. Patients alive at the time of analysis will be censored at the date of last assessment. - The DCR will be measured from the date of treatment initiation to the date of onset of the first objective response (CR / PR / SD) until the final visit. - Toxicity will be evaluated during the treatment until 30 days after the last dose of study medication - Gene mutational status will be analyzed at baseline and at the disease progression date - The Quality of Life will be assessed from the date of enrollment, every 8 weeks, until the end-of-treatment visit | — |
Countries
Italy
Contacts
Public ContactUOC Oncologia Medica 2
Istituto Oncologico del Veneto IRCCS
Outcome results
None listed