PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF THE EFFICACY AND SAFETY OF PF 02341066 VERSUS STANDARD OF CARE CHEMOTHERAPY (PEMETREXED OR DOCETAXEL) IN PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) HARBORING A TRANSLOCATION OR INVERSION EVENT INVOLVING THE ANAPLASTIC LYMPHOMA KINASE (ALK) GENE LOCUS

• Conditions: ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) HARBORING A TRANSLOCATION OR INVERSION EVENT INVOLVING THE ANAPLASTIC LYMPHOMA KINASE (ALK) GENE LOCUS; MedDRA version: 13.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2009-012595-27-BG
• Lead Sponsor: Pfizer Inc. 235 East 42nd Street, New York, NY 10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-02-23
• Last Update Posted: 11 April 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 318

Inclusion Criteria

1. Histologically or cytologically proven diagnosis of NSCLC that is locally advanced or
metastatic
2. Positive for translocation or inversion events involving the ALK gene locus (e.g.
resulting in EML4-ALK fusion) as determined by an ALK break apart FISH assay and
defined by an increase in the distance of 5’ and 3’ ALK probes or the loss of the 5’ probe
3. Patients must have had progressive disease after only one prior chemotherapy regimen. This regimen must have been platinum-based and may have included maintenance therapy. Patients must be considered appropriate candidates for additional chemotherapy with either single-agent pemetrexed or single-agent docetaxel Includes patients who received one prior platinum-based chemotherapy for treatment of de novo Stage IIIB/IV NSCLC.
- Includes patients who have received one prior platinum-based chemotherapy in the adjuvant setting following surgical resection for early disease and whose disease has recurred within 6 months of completion of prior chemotherapy
- Includes patients who received one prior platinum-based chemotherapy in
combination with radiation therapy for Stage III locoregional disease and whose
disease has recurred within 6 months of completion of prior chemotherapy
- Includes patients who received 2 prior platinum-based chemotherapy regimens, if the first regimen was given as adjuvant therapy or was given in combination with
radiation therapy for locally advanced disease
- Includes patients who have received prior treatment with an EGFR tyrosine kinase
inhibitor, such as erlotinib or gefitinib, providing these patients have also received
only one prior platinum-based chemotherapy regimen as in one of the scenarios
described above
4. Patients with brain metastases are eligible if asymptomatic or if treated must be neurologically stable for at least 2 weeks and is not taking any medications contraindicated in Exclusion Criteria #12-14
5. Any prior chemotherapy or major surgeries must have been completed at least 4 weeks prior to initiation of study medication. Any prior radiation (except for 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 been completed 48 hours prior to the start of
study treatment.Any acute toxicity must have recovered to = Grade 1 (except alopecia)
6. Tumors must have measurable disease as per RECIST (version 1.1);
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)
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; however, for patients who if
randomly assigned to Arm B must receive docetaxel, ALT and/or AST must not be >
1.5 x ULN concomitant with alkaline phosphatase > 2.5 x ULN
-Total serum bilirubin =1.5 x ULN however for patients who if randomly assigned to
Arm B must receive docetaxel, total serum bilirubin must be = 1 x ULN
Bone marrow function
- Absolute neutrophil count (ANC) =1500/µL
- Platelets =100,000/µL
- Hemoglobin =8.0 g/dL
Renal function
- Creatinine clearance (based on modified Cockcroft-Gaul

Exclusion Criteria

1. Current treatment on another therapeutic clinical trial
2. Prior therapy specifically directed against ALK
3. Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function, carcinomatous meningitis, or leptomeningeal disease
4. Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack.
5. Ongoing cardiac dysrhythmias of NCI CTCAE Grade =2, uncontrolled atrial fibrillation of any grade, or QTc interval >470 msec
6. Previous treatment with PF-02341066
7. Patients who if randomly assigned to Arm B must receive pemetrexed and who have NSCLC with predominantly squamous cell carcinoma
8. Patients who if randomly assigned to Arm B must receive docetaxel and who have
peripheral neuropathy with Grade > 2
9. Patients who if randomly assigned to Arm B must receive docetaxel and who have had a hypersensitivity reaction to medications formulated with polysorbate 80
10. [Deleted per Amendment #7]
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, voriconazole, 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. 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 localized cervical cancer, or localized and presumed cured prostate cancer) within the last 3 years
16. For Japan only: patients who have following complications or symptoms:
- Serious wound such as chronic wound, or grade =3 gastrointestinal ulcer
- Serious gastrointestinal symptoms such as grade =3 diarrhea
17. Other severe acute or chronic medical 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