Cancer of the lung with special characteristics (nonsquamous histology and ALK fusion gene event)

Phase 1

• Conditions: non-small cell lung cancer (NSCLC); MedDRA version: 14.0Level: PTClassification code 10029519Term: Non-small cell lung cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-021336-33-DK
• Lead Sponsor: Pfizer Inc 235 East 42nd Street, New York, NY10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-06-22
• Last Update Posted: 13 March 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 334

Inclusion Criteria

1. Histologically or cytologically proven diagnosis of locally advanced not suitable for local treatment, recurrent and metastatic non-squamous cell carcinoma of
the lung.
2. Positive for translocation or inversion events involving the ALK gene locus (eg, resulting in EML4-ALK fusion) as determined by an ALK break apart FISH assay and
defined by an increase in the distance between 5’ and 3’ ALK probes or the loss of the 5’ probe.
3. No prior systemic treatment for locally advanced or metastatic disease (exception below):
• Prior adjuvant chemotherapy for Stage I-III or combined modality chemotherapyradiation for locally advanced disease allowed if completed >12 months prior to randomization.
4. Patients with brain metastases are only eligible if treated and neurologically stable with no ongoing requirement for corticosteroids, eg, dexamethasone, for at least 2 weeks and are not taking medications contraindicated in Exclusion Criteria
5. Any major surgeries must have been completed at least 4 weeks prior to initiation of study medication. Any prior radiation (except palliative)or minor surgeries/procedures must have been completed at least 2 weeks prior to the initiation of study medication. Palliative radiation (= 10 fractions) must have completed 48 hrs prior to crizotinib therapy commencing. Any acute toxicity must have recovered to = Grade 1 (except alopecia).
6. Tumors must have measurable disease as per RECIST
7. Female or male, 18 years of age or older (for patients enrolled in Japan: consent from a legally acceptable representative is required for all patients who are under20 years old).
8. ECOG performance status 0-2.
9. Adequate organ function as defined by the following criteria: Hepatic function:
• Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) = 2.5 x upper limit of normal (ULN), or AST and ALT = 5 x ULN if liver function abnormalities are due to underlying malignancy.
• Total serum bilirubin =1.5 x ULN. Bone marrow function:
• Absolute neutrophil count (ANC) =1500/µL.
• Platelets =100,000/µL.
• Hemoglobin =9.0 g/dL. Renal function:
• Creatinine clearance (based on modified Cockcroft- Gault formula) =60 ml/min.
10. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study prior to enrollment.
11. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures including completion of PRO measures.
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 268
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66

Exclusion Criteria

1. Current treatment on another therapeutic clinical trial.
2. Prior therapy directly targeting ALK.
3. Carcinomatous meningitis, or leptomeningeal disease.
4. Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function.
5. Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, or cerebrovascular accident including transient ischemic attack. Appropriate treatment with anticoagulants is permitted.
6. Ongoing congestive heart failure.
7. Ongoing cardiac dysrhythmias of NCI CTCAE Grade =2, uncontrolled atrial fibrillation of any grade, or QTc interval >470 msec.
8. Peripheral neuropathy with Grade =1 (CTCAE version 4.0).
9. Known interstitial fibrosis or interstitial lung disease.
10. Previous treatment with crizotinib.
11. Pregnancy or breastfeeding.
12. Use of drugs or foods that are known potent CYP3A4 inhibitors including but not limited to amprenavir, atazanavir, clarithromycin, delavirdine, diltiazem, erythromycin, indinavir, itraconazole, ketoconazole, miconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, verapamil, voriconzole, and grapefruit or grapefruit juice.
13. Use of drugs that are known potent CYP3A4 inducers including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, tipranavir, ritonavir, and St. John’s wort.
14. Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited aripiprazole, ergotamine, halofantrine, pimozide, triazolam, astemizole*, cisapride*, and terfenadine* (* withdrawn from U.S. market).
15. Prior malignancy (other than current NSCLC):
patients will not be eligible if they have evidence of active malignancy (other than non-melanoma skin cancer or in situ cervical cancer, or localized and presumed cured prostate cancer) within the last 3 years.
16. Known HIV infection.
17. Other severe acute or chronic medical (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified