| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| treatment of locally advanced or metastatic non-small cell lung cancer after failure of one prior chemotherapy regimen in patients with tumors harboring a translocation or inversion event involving the ALK gene locus. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate that PF-02341066 (Arm A) is superior to standard of care chemotherapy, pemetrexed or docetaxel (Arm B), in prolonging PFS in patients with advanced NSCLC whose tumors harbor a translocation or inversion event involving the ALK gene locus and who have received only one prior chemotherapy regimen for advanced NSCLC and this regimen must have been platinum-based |
|
| E.2.2 | Secondary objectives of the trial |
| - To assess secondary measures of clinical efficacy including objective response rate(ORR), duration of response (DR), disease control rate (DCR) at 6 and 12 weeks, and overall survival (OS) in both treatment arms - To assess the safety and tolerability of PF-02341066 compared to pemetrexed or docetaxel - To compare patient reported outcomes (PRO) of health-related quality of life (HRQoL), disease/treatment-related symptoms of lung cancer, and general health status in both treatment arms - To characterize the effects of PF-02341066 at therapeutic doses on QTc interval in this patient population - To determine PK in this patient population using population PK (POPPK) methods and explore correlations between PK, response and/or safety findings - To explore the relationship of ALK gene fusion to the presence of ALK protein and fusion transcript - To correlate modulation of soluble biomarkers to PK and outcome measures |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 appropriately treated and neurologically stable for at least 2 weeks and is not taking any medications contraindicated in Exclusion Criteria #11-12 5. Any prior chemotherapy or major surgeries must have been completed at least 4 weeks prior to initiation of study medication. Any prior radiation or minor surgeries/procedures must have been completed at least 2 weeks prior to the initiation of study medication. Any acute toxicity must have recovered to ≤ Grade 1 (except alopecia) 6. Tumors must be measurable as per RECIST (version 1.0) - At least one target lesion and which is measurable in at least one dimension of ≥ 20 mm by conventional computerized tomography (CT) or magnetic resonance imaging (MRI), or ≥ 2 x the reconstruction interval by spiral CT must be present - Target lesions can be chosen from a previous irradiated area if lesions in those areas have documented progression 7. Female or male, 18 years of age or older 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 xupper 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 (except patients with documented Gilbert s syndrome); 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/uL - Platelets >/=100,000/uL - Hemoglobin >/=9.0 g/dL Renal function - Creatinine clearance (based on modified Cockcroft-Gault formula) ≥ 45 ml/min 10. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment |
|
| E.4 | Principal exclusion criteria |
| 1. Current treatment on another therapeutic clinical trial 2. Prior therapy specifically directed against ALK 3. Spinal cord compression, carcinomatous meningitis, or leptomeningeal disease 4. Any of the following within the 6 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, 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 (CTCAE version 3.0) 9. Patients who if randomly assigned to Arm B must receive docetaxel and who are receiving concomitant medications formulated with polysorbate 80 10. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy) 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 in situ cervical cancer, or localized and presumed cured prostate cancer with PSA < ULN) within the last 5 years 16. 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| PFS based on RECIST version 1.0 (confirmed by independent radiology review) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
Print
