Adenocarcinoma of the lung harbouring ROS1 translocation C34.9
Conditions
Interventions
Group 1: Crizotinib 250 mg, oral, twice daily, untill progression, intolerability or beyond progression if clinically indicated
Sponsors
Universitätsklinikum Köln
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patients with adenocarcinoma of the lung that is locally advanced or metastatic independent from the number of prior lines of therapy, i.e. including non-pretreated patients (UICC stage IIIB or IV) 2. Positive for ROS1 translocation by central FISH-testing 3. Ability to swallow pills 4. Age > 18 years 5. ECOG performance status 0 to 2 6. Life expectancy of at least 12 weeks 7. Disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) 8. Any prior treatment (chemotherapy, radiation or surgery) must have been completed at least 2 weeks prior to initiation of study medication 9. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 14 days prior to screening: - Hemoglobin = 8.0 g/dL - Absolute neutrophil count (ANC) = 1,000 /mm3 - Platelet count = 50 000/µL - Total bilirubin = 2 x upper limit of normal (ULN) - Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (AP) = 2,5 x ULN or = 5 x ULN in case of liver involvement - PT-INR/PTT = 1.5 x ULN - Serum creatinine = 2 times ULN - Calculated creatinine clearance (CLcr) = 40 ml/min (Cockcroft-Gault formula) 10. Written informed consent 11. Negative serum pregnancy test within 3 days prior to start of dosing premenopausal women. Women of non-childbearing potential may be included without serum pregnancy test if they are either surgically sterile or have been postmenopausal for = 1 year. 12. Fertile men and women must have an effective method of contraception during treatment and for at least 3 months after completion of treatment as directed by their physician.
Exclusion criteria
Exclusion criteria: 1. Previous treatment with specific ALK or ROS1 inhibitors 2. Current treatment within another therapeutic clinical trial 3. Other history of ongoing malignancy that would potentially interfere with the interpretation of efficacy (early stage or chronic disease is allowed if not requiring active therapy or intervention and being under control) 4. Pregnancy or breastfeeding 5. Use of drugs or foods that are known potent CYP3A4 inhibitors, including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole and grapefruit or grapefruit juice 6. Use of drugs that are known potent CYP3A4 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John’s wort 7. Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to dihydroergotamine, ergotamine, pimozide, astemizole, cisapride, and terfenadine 8. Active CNS metastases. Patients with brain metastasis are eligible if asymptomatic for = 14 days before starting study medication and off corticosteroids. 9. History of or known carcinomatous meningitis or leptomeningeal disease 10. Known diagnosis of HIV, active hepatitis B and/or C (testing is not mandatory) 11. Any person being in an institution on assignment of the respective authority against his/her own will 12. Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information 13. Ongoing cardiac dysrhythmias of CTCAE grade =2, uncontrolled atrial fibrillation of any grade or QTcF interval > 470ms 14. Patients with known interstitial fibrosis or interstitial lung disease 15. Any of the following within 3 months prior to first crizotinib administration: Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate efficacy of crizotinib treatment in advanced adenocarcinoma of the lung harbouring ROS1 fusion genes as assessed by central testing; primary endpoint: objective response rate (ORR); evaluation criteria: investigator assessed RECIST v.1.1 analysis | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To evaluate the efficacy of crizotinib monotherapy regarding the secondary endpoints: overall survival (OS), progression free survival (PFS), duration of response (DR), time to tumor response, disease control rate (DCR) in advanced adenocarcinoma of the lung harbouring ROS1 fusion genes as assessed by central testing (evaluation criteria: investigator assessed RECIST v1.1) 2. To evaluate the efficacy of crizotinib treatment in the patient subgroup with ROS1 translocation confirmed by the CAGE technology regarding the objective response rate (ORR) (evaluation criteria: investigator assessed RECIST v1.1) 3. To evaluate the efficacy of crizotinib treatment by an independent radiologic review process regarding the objective response rate (ORR), overall survival (OS), progression free survival (PFS), duration of response (DR), time to tumor response, disease control rate (DCR) (evaluation criteria: RECIST v1.1 by independent radiologic review) 4. To evaluate safety and tolerability of crizotinib monotherapy (evaluation criteria: NCI CTCAE 4.0) 5. To assess patient reported outcomes (PRO) of health-related quality of life (HRQoL), disease/treatment related symptoms of lung cancer, and general health status | — |
Countries
Germany, Spain, Switzerland
Contacts
Public ContactSebastian Michels
Uniklinik Köln Klinik I für Innere Meidzin/Lung Cancer Group Cologne
Outcome results
None listed