Advanced RET-rearranged non-small cell lung cancer MedDRA version: 21.1 Level: LLT Classification code 10064049 Term: Lung adenocarcinoma metastatic System Organ Class: 100000004864
Conditions
Interventions
Trade Name: CABOMETYX - 20 MG- COMPRESSA RIVESTITA CON FILM- USO ORALE- FLACONE (HDPE)- 30 COMPRESSE
Product Name: CABOMETYX
Product Code: [NA]
Pharmaceutical Form: Tablet
INN or Proposed INN: cabozan
Sponsors
ALMA MATER STUDIORUM UNIVERSITà DI BOLOGNA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Locally advanced, relapsed or metastatic non-small cell lung cancer – stage IIIB/IV according to 7th International Association for the Study of Lung Cancer (IASLC) classification ¿ 2. Ability to understand and willingness to sign informed consent prior to initiation of any study procedures. ¿ 3. Pathologically (histology or cytology) confirmed diagnosis of non- small cell lung carcinoma. ¿ 4. RET gene rearrangement by local laboratory analysis with an approved standard method (FISH or Next Generation Sequencing Panel). An archival tumor sample must be available for central laboratory confirmation. ¿ 5. Male or female and = 18 years of age ¿ 6. Life expectancy = 12 weeks ¿ 7. Have progressed after or during at least one standard anticancer ¿ treatment 8. Have measurable disease as per Response Evaluation Criteria in ¿Solid Tumors, version 1.1 (RECIST 1.1); clear radiological evidence of disease progression after first-line therapy must be documented; no previous radiotherapy on the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression ¿ 9. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1 10. Subjects must have adequate organ function including the following: • Absolute neutrophil count > 1.5 x 10^9/L ¿ • Platelet count > 100 x 10^9/L ¿ • Haemoglobin > 90 g/L ¿ • ALT 50 ml/min (measured or calculated by Cockcroft and Gault equation, confirmation of creatinine clearance is only required when creatinine is > 1.5 times ULN) • Lipase =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization. Systemic treatment with radionuclides within 6 weeks before randomization. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. 2. Previous treatment with cabozantinib. ¿ 3. Gastrointestinal disorders likely to interfere with absorption of the study drug. 4. Subjects with gastrointestinal disorders associated with a high risk of perforation of fistula formation. 5. Subjects with active peptic ulcer or with a history of clinically ¿significant GI bleeding within 6 months before the first dose of study treatment. 6. Patients requiring full-dose anticoagulation therapy any time prior to enrollment. 7. Current use of aspirin, clopidogrel, ticlopidine. 8. Patients with tumors invading major pulmonary vessels and/or with cavitating pulmonary lesions. 9. Major surgery within the last four weeks. Complete wound healing from major surgery must have occurred 1 month before randomization and from minor surgery at least 10 days before randomization. Subjects with clinically relevant ongoing complications from prior surgery are not eligible. 10. Subjects with clinical or radiological signs of pulmonary hemorrhage within 3 months before the first dose of study treatment. 11. Symptomatic CNS or leptomeningeal lesions, not previously treated with radiotherapy. Untreated central nervous system (CNS) or leptomeningeal metastases are allowed if asymptomatic. Patients with symptomatic CNS or leptomeningeal lesions will be allowed to participate in this study if previously treated with radiotherapy and on stable dose of corticosteroids and/or anticonvulsants for > 10 days or not requiring such medication. Radiotherapy must have been completed a minimum of 4 weeks prior to registration, and patients must have recovered from AEs related to radiotherapy to < grade 1 (except alopecia). 12. History of congenital platelet function defect. 13. Patient unable to swallow tablets¿ 14. Corrected QT interval greater than 500 ms (Fridericia formula) 15. Clinically significant, uncontrolled heart diseases: - Unstable angina within 6 months prior to screening ¿ ¿ - Myocardial infarction within 6 months prior to screening ¿ ¿ - History of documented congestive heart failure - Uncontrolled hypertension defined by a Systolic Blood Pressure , with or without antihypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening ¿ - Ventricular arrhythmias, Supraventricular and nodal arrhythmias not controlled with ¿medication ¿ - Congenital history of QT syndrome. 16. Diagnosed with or treated for another malignancy within 3 years ¿before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type may be enrolled in the study if they have undergone complete resection and no evidence of active disease is present. ¿ 17. Any type of systemic anticancer agent within 3 weeks of first dose of study treatment, or within 5 half- lives of the agent whichever is shorter (subjects on LHRH or GnRH agonists may be maintained on these agents) ¿ 18. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject’s safety, provision of informed consent, or compliance to st
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the activity of cabozantinib in pretreated, advanced RET-rearranged non-small cell lung cancer patients;Secondary Objective: To evaluate safety and efficacy of cabozantinib in pretreated patients with advanced RET-rearranged non-small cell lung cancer;Primary end point(s): ORR. The primary end-point is objective tumor response (percentage of patients who obtain complete or partial responses) that will be evaluated according to standard RECIST 1.1 criteria and will be based on central imaging assessment and review by Independent Review Committee (IRC). The assessment will be performed every 8 weeks. Data will be reported as percentage of complete responses (CRs), partial responses (PRs), stable disease (SD) and progressive disease (PD). Exact binomial method will be used to estimate the response rate (CR+PR) and its 95% confidence interval. Patients with no tumor assessment after baseline will be classified as non-responders.;Timepoint(s) of evaluation of this end point: 12-18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Toxicity: the assessment of safety will be based mainly on the frequency of adverse events; toxicity will be measured according to NCI Common Toxicity Criteria Adverse Event (CTCAE), version 4.03. - Disease Control Rate (DCR), measured as the sum of complete and partial responses + stable disease - Progression Free Survival (PFS), measured from the first treatment intake to the date of disease progression or death -Overall Survival (OS), measured from the first treatment intake to the date of death by any cause - Duration of Response (DOR), measured from the first treatment intake to the date of disease progression or death - Detection of potential mechanisms of acquired resistance to RET inhibition by sequencing of DNA extracted from tumor-rebiopsy at the time of disease progression (and at least 28 days from the last dose of cabozantinib) optional;Timepoint(s) of evaluation of this end point: 12-18 months | — |
Countries
Italy
Contacts
Public ContactUOC di Oncologia Medica, Azienda Os
Alma Mater Studiorum Università di Bologna
Outcome results
None listed