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: 19.0Level: 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-DE
• Lead Sponsor: Pfizer Inc 235 East 42nd Street, New York, NY10017 US

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-31
• Last Update Posted: 9 January 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 or metastatic non squamous non
small 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
chemotherapy-radiation for locally advanced disease allowed if
completed >12 months prior to documented disease progression.
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 # 12-14 (in the protocol).
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 under 20 years old). For patients in India upper age limit is 65 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. Patients
enrolled in France with ALT =3 and =5 x ULN must not have evidence of advanced fibrosis as detected by Fibrotest >0.48
- 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 legal 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.
12. Male patients able to father children and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for 90 days after the last dose of assigned treatment. Male patients randomized to Arm B must use highly effective method of contraception
for a total of 180 days after last dose of chemotherapy. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 268
F.1

Exclusion Criteria

1. Current treatment on another therapeutic clinical trial. Patients who are investigational site staff members or relatives of those site staff members, or patients who are Pfizer employess directly involved in the conduct of the 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 machine-read ECG with QTc interval >470 msec.
8. Peripheral neuropathy with Grade =1 (CTCAE version 4.0).
9. History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease, including a
history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not history of prior radiation pneumonitis.
10. Previous treatment with crizotinib.
11. Pregnancy or breastfeeding.
12. Use of drugs or foods that are known potent CYP3A4 inhibitors
within 7 days prior to the first dose of crizotinib, including but not
limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconzole, and grapefruit or grapefruit juice. The topical use of these medications (if applicable), such as 2%
ketoconazole cream, may be allowed.
13. Use of drugs that are known potent CYP3A4 inducers within 12 days prior to the first dose of crizotinib, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.
14. Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to dihydroergotamine, ergotamine, pimozide, 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 nonmelanoma 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 end-stage renal disease on hemodialysis. 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