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Treatment of advanced adenocarcinoma of the lung

Phase 1
Conditions
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
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2013-002737-38-DE
Lead Sponsor
niversity of Cologne
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Not specified
Target Recruitment
30
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

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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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