Adult patients with either firstly diagnosed or relapsed advanced adenocarcinoma of the lung harbouring ROS1 translocation MedDRA version: 20.0 Level: LLT Classification code 10025032 Term: Lung adenocarcinoma NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Xalkori
Product Name: Xalkori
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Xalkori
CAS Number: 877399-52-5
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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) Positive result of ROS1 translocation by central FISH-testing is mandatory. Ability to swallow pills Age > 18 years ECOG performance status 0 to 2 Life expectancy of at least 12 weeks Disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) Any prior treatment (chemotherapy, radiation or surgery) must have been completed at least 2 weeks prior to initiation of study medication. 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 (CRCL) = 40 ml/min (Cockcroft-Gault formula) Written informed consent 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. 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. Effective methods of contraception result in a low failure rate (i.e. less 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the Investigator, acceptable methods of contraception may include total abstinence where lifestyle of the patient ensures compliance (Periodic abstinence and withdrawal are not acceptable methods of contraception). 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Previous treatment with specific ALK or ROS1 inhibitors Current treatment within another therapeutic clinical trial 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) Pregnancy or breastfeeding 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 Use of drugs that are known potent CYP3A4 inducers, including but not limited to carbamazepine, Phenobarbital, phenytoin, rifabutin, rifampin, and St. John’s wort Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to dihydroergotamine, ergotamine, pimozide, astemizole, cisapride, and terfenadine. Active CNS metastases, patients with brain metastasis are eligible if asymptomatic for = 14 days before starting study medication and off corticosteroids History of or known carinomatous meningitis or leptomeningeal disease Known diagnosis of HIV, active hepatitis B and/or C (testing is not mandatory) Any person being in an institution on assignment of the respective authority against his/her own will 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 Ongoing cardiac dysrhythmias of CTCAE grade =2, uncontrolled atrial fibrillation of any grade or QTcF interval > 470ms History of extensive disseminated/bilateral or known presence of interstitial fibrosis or interstitial lung disease of any grade, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not history of prior, radiation pneumonitis. Any of the following within 3 months prior to first crizotinib administration: Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: ?? To evaluate the efficacy of crizotinib monotherapy regarding the secondary endpoints: OS, PFS, DR, TTR, DCR in advanced adenocarcinoma of the lung harbouring ROS1 fusion genes as assessed by central testing; evaluation criteria: investigator assessed RECIST v1.1 ? To evaluate safety and tolerability of crizotinib monotherapy (evaluation criteria: NCI CTCAE 4.0) ? 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), OS, PFS, DR, TTR , DCR; evaluation criteria: investigator assessed RECIST v1.1 ? To evaluate the efficacy of crizotinib treatment by an independent radiologic review process regarding the ORR, OS, PFS, DR, TTR, DCR; evaluation criteria: RECIST v1.1 by independent radiologic review ? To asses patient reported outcomes (PRO) of HRQoL, disease/treatment related symptoms of lung cancer, and general health status (EORTC QLQ-C30 and QLQ-LC13) ;Primary end point(s): Objective response rate defined as complete and partial responses (evaluation criteria: investigator assessed RECIST v1.1) ;Timepoint(s) of evaluation of this end point: ORR will be evaluated by CT/MRI scans every 6 weeks (+/- 3d). After the 4th staging (C7D1), staging interval will be prolonged to 8 weeks. After the 7th staging (C13D1), the staging intervals will be prolonged to 12 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: DCR will be evaluated at 6, 12, 18 (every 6) weeks (+/- 3d). After the 4th staging (C7D1), staging interval will be prolonged to 8 weeks. After the 7th staging (C13D1), the staging intervals will be prolonged to 12 weeks. ; Secondary end point(s): ? Median overall survival (OS), median progression free survival (PFS), median duration of response (DR), median time to tumor response (TTR), 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) ? Type, incidence, severity, seriousness and relationship to study medications of adverse events (evaluation criteria: NCI CTCAE 4.0) ? CAGE ROS1 translocation subgroup: Objective response rate defined as complete and partial responses according, median overall survival (OS), median progression free survival (PFS), median duration of response (DR), median time to tumor response (TTR), disease control rate (DCR) (evaluation criteria: investigator assessed RECIST v1.1) ? 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 (TTR), disease control rate (DCR) (evaluation criteria: RECIST v1.1 by independent radiologic review) ? Health-related quality of life (HRQoL), disease/treatment related symptoms of lung cancer, and general health status according to EORTC QLQ-C30 and EORTC QLQ-LC13. | — |
Countries
Austria, Germany, Spain, Switzerland
Contacts
Public ContactLung Cancer Group Cologne
Lung Cancer Group Cologne
Outcome results
None listed