Advanced/metastatic lung cancer and FGF, VEGF, or PDGF-related genetic alterations MedDRA version: 18.1 Level: PT Classification code 10050017 Term: Lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Clovis Oncology Italy s.r.l.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patient aged = 18 years. 2. Histologically or cytologically confirmed advanced/metastatic SCLC or NSCLC. 3. Documented radiographic disease progression following at least one line of therapy in the advanced/metastatic setting: • Patient must be refractory to all appropriate and approved therapies. 4. Any of the following tumor tissue based genetic alterations known prior to screening: • FGFR1, FGFR2, FGFR3, VEGFA, or PDGFRa amplification • Any FGFR1, FGFR2, or FGFR3 fusion • FGFR1, FGFR2, or FGFR3 activating mutation (see Appendix 5 for specific qualifying FGFR mutations) 5. Availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample sufficient for the central confirmation of the genetic alteration and exploratory analyses 6. Documented progressive extra central nervous system (CNS) disease at the time of inclusion. 7. At least one extra CNS measurable lesion according to RECIST 1.1 (with the last objective assessment no more than 4 weeks before the first dose of lucitanib). In addition, one prior measurable evaluation within a maximum of 3 months, if available, should be collected to assess tumor kinetics. 8. At least one prior treatment line in the advanced/metastatic setting. 9. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 10. Ability to take oral medication. 11. Adequate bone marrow function: absolute neutrophil count (ANC) = 1.0 × 109/L, platelet counts = 100 × 109/L, and hemoglobin = 9 g/dL. 12. Adequate renal function defined as: calculated clearance = 60 mL/minute (assessed with modification of diet in renal disease [MDRD] formula), proteinuria dipstick =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. Carcinoid history 2. Known symptomatic CNS metastases not controlled by prior surgery or radiotherapy and/or low dose steroids. 3. Active second malignancy; i.e., patient known to have potentially fatal cancer present for which he/she may be (but is not necessarily) currently receiving treatment . 4. Chemotherapy within 6 months or bone marrow transplant (BMT) within 2 years prior to the first dose of lucitanib in patients with a history of cancer other than SCLC or NSCLC and with no current evidence of disease. 5. Anti cancer treatment for lung cancer within 28 days or 5 half lives, whichever is longer, before the first dose of lucitanib. 6. Investigational treatment within 28 days before the first dose of lucitanib 7. Wide field radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks before the first dose of lucitanib. 8. Tumors that are invading a major vessel 9. NSCLC tumors abutting (adjacent and proximal) to a major vessel. 10. History of major surgical procedure or significant trauma within 28 days prior to the first dose of lucitanib, or non study related minor surgical procedure within 14 days prior to the first dose of lucitanib. 11. Ongoing AEs from surgery or prior anti cancer therapies, including radiation, targeted, or cytotoxic therapies without resolution of any Grade 2 or greater side effects to Grade = 1. 12. History of gross hemoptysis within 3 months prior to first dose of lucitanib or history of hemoptysis = ½ teaspoon (2.5 mL) of blood per day for a day or more within 1 week prior to the first dose of lucitanib. 13. History of coagulopathy or hemorrhagic disorders. 14. History of abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 3 months prior to first dose of lucitanib 15. Clinically significant non-healing wound, ulcer, or bone fracture. 16. Uncontrolled hypertension (defined as systolic blood pressure ([SBP]) = 140 mmHg and/or diastolic blood pressure ([DBP]) = 90 mmHg) with optimized anti hypertensive therapy. •The requirement for > 2 anti hypertensives to control hypertension at the time of enrolment is exclusionary. 17. Cardiovascular disease or conditions, including: a. Congestive heart failure (New York Heart Association functional classification = 2) or requiring therapy. b. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, and/or stenting within 6 months before the first day of study drug administration. c. Ventricular and/or supra-ventricular arrhythmia requiring therapy. d. Conduction disturbance including QTC prolongation (defined as a QTC interval > 470 ms according to Fridericia’s correction as observed by the investigator) or other significant ECG abnormalities including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or bradycardia (heart rate < 50 bpm); history of severe arrhythmia;, or history of familial arrhythmia [e.g., Wolff-Parkinson-White syndrome]). e. Risk factors for or concomitant treatment with medications known to prolong QTC interval and that are clearly associated with Torsades de Pointes (see Appendix 2). 18. Patients with history of thromboticdisorders a. Any history of venous thrombotic events, deep vein thrombosis (with the exception of catheter related deep vein thrombosis), or pulmonary embolism within 6 months prior to the first dose of lucitanib. b. Any history of arterial thrombotic events, cerebrovascular a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the objective response rate (ORR) of lucitanib in patients with advanced/metastatic lung cancer and fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), or platelet derived growth factor (PDGF) related genetic alterations ;Secondary Objective: - To evaluate the clinical benefit rate (CBR), progression-free survival (PFS), duration of the response (DR) and overall survival (OS). - To evaluate the kinetics of tumor size change prior to and after lucitanib exposure. - To evaluate the safety profile of lucitanib. - To collect additional information on the pharmacokinetic (PK) profile of lucitanib.;Primary end point(s): ORR Proportion of patients with a confirmed complete response (CR) or a confirmed partial response (PR), as best overall response according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 criteria;Timepoint(s) of evaluation of this end point: Baseline and every 8 weeks (every 2 cycles) and at the end of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -ORR: Proportion of patients with a confirmed Complete Response (CR) or a confirmed Partial Response (PR), as best overall response according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 criteria -CBR: Proportion of patients with a confirmed CR, a confirmed PR, or a prolonged stable disease (SD) (>6 months), as best overall response according to RECIST 1.1 PFS, DR, duration of clinical benefit, OS, tumor growth kinetics. -Adverse Events, laboratory abnormalities, physical examinations including vital signs, electrocardiogram (ECG), and ventricular ejection fraction (LVEF) abnormalities. -Population PK;Timepoint(s) of evaluation of this end point: CBR, PFS, Duration of response, Duration of clinical benefit, Overall survival, Adverse events - monitored throughout study Tumour growth kinetics - Baseline and every 8 weeks Laboratory examinations, physical examination, ECOG performance status, vital signs - Screening or D1 (pre-dose), D4 (physical examination and vital signs only), D14, D28, D56, every 4 weeks thereafter and at end of study ECG and LVEF - Screening or on D1 (pre-dose), D1 (ECG only: 2 h post-dose), D14 (ECG only: pre-dose, 2h and 3h post-dose), D28, D56, every 8 weeks thereafter and at end of study PK - D14 (pre-dose and 2h post-dose) and pre-dose on D28, D56 and D84 PG - D1 (pre-dose) PD - D1 (pre-dose), D14 (pre-dose) and end of study visit 24h after last dose | — |
Countries
France, Germany, Italy, Spain, United States
Contacts
Public ContactJason B Litten
Clovis Oncology, Inc.
Outcome results
None listed