A trial of alectinib for treatment of ALK-rearranged non-small cell lung cancer.
- Conditions
- ALK-rearranged non-small cell lung cancer (NSCLC) after disease progression on prior ALK inhibitor therapyMedDRA version: 20.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003924-22-FR
- Lead Sponsor
- ROCHE SAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 73
- Patients with histologically or cytologically confirmed locally advanced or metastatic NSCLC (Stage IIIB or IV accordingly to American Joint Committee on Cancer [AJCC] classification)
- Male or female = 18 years old
- Life expectancy of at least 12 weeks, in the opinion of the Investigator
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 2
- Patients having:
a) contributive biopsy performed on fresh tissue (FFPE blocks required) taken after progression on previous therapy showing:
- presence of anaplastic lymphoma kinase (ALK) rearrangement, assessed by IHC and confirmed by FISH,
- absence of resistance mechanism to alectinib assessed by the Biomarkers Board:
1. ALK I1151Tins I1171N/S, V1180L and G1202R mutations (known to induce a resistance to alectinib),
2. epidermal growth factor receptor (EGFR) exon 19 deletions, L858R mutation or Kirsten rat sarcoma viral oncogene homolog (KRAS) codon 12, 13 or 61 mutations,
3. High level of MET amplification,
4. tumor histologic transformation into small cell lung cancer.
b) disease progression, limited to CNS without possibility of tissue biopsy,
c) non-contributive molecular analyses (no enough tumor cells or DNA amount or failure of analyses for technical reasons): inclusion is at investigator discretion (his decision taken upon Biomarker Board recommendation)
- History of crizotinib exposure
- Adequate hematologic function
- Adequate renal function
- For all females of childbearing potential, a negative pregnancy test must be obtained within three days before starting study drug
- For women who are not postmenopausal (= 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 90 days after the last dose of study drug
- For men: agreement to remain abstinent or use a barrier method of contraception (e.g., condom) during the treatment period and for at least 90 days after the last dose of study drug and agreement to refrain from donating sperm during this same period
- Patient has national health insurance coverage
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 63
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
- Prior therapy with other ALK inhibitors than crizotinib (including alectinib)
- Patients with symptomatic CNS metastases who are neurologically unstable or require increasing doses of steroids within one week prior to Day 0 to manage CNS symptoms (Patients with brain or leptomeningeal metastases are allowed, symptomatic disease is allowed as long as symptoms are controlled and stable and prior treatment with whole brain radiation or gamma knife must have been completed at least 14 days prior to Day 0 and patients must be clinically stable)
- Patients with progression limited to CNS and eligible to a focal treatment (surgery or stereotaxic radiotherapy)
- Liver disease characterized by: Alanine transaminase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) (= 5×ULN for patients with concurrent liver metastasis) confirmed on two consecutive measurements
OR Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices.
OR Acute viral or active autoimmune, alcoholic, or other types of hepatitis
- Patients with baseline QTc > 470 ms or patients with symptomatic bradycardia.
- Pregnant or lactating women
- Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry
- Serious, uncontrolled infections or current known infection with human immunodeficiency virus (HIV)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method