A phase II trial to evaluate the efficacy and safety of Crizotinib treatment in advanced adenocarcinoma of the lung harbouring ROS1 translocations
- Conditions
- Adenocarcinoma of the lung harbouring ROS1 translocationC34.9Bronchus or lung, unspecified
- Registration Number
- DRKS00005409
- Lead Sponsor
- niversitätsklinikum Köln
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 30
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.
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
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) after 6 weeks of treatment according to RECIST 1.1
- Secondary Outcome Measures
Name Time Method Overall survival (OS),<br>progression free survival (PFS), duration of response (DR), time to tumor response, disease control rate (DCR) at 6, 12 and 24 weeks