E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced non-small cell lung cancer (NSCLC) harboring a translocation or inversion event involving the anaplastic lymphoma kinase (ALK) gene locus |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
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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 assess the anti-tumor efficacy of oral single agent PF-02341066 administered to patients with advanced NSCLC after failure of at least one line of chemotherapy and harbor a translocation or inversion event involving the ALK gene locus as measured by ORR |
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E.2.2 | Secondary objectives of the trial |
To assess secondary measures of clinical efficacy including DR, DCR at 6 and 12 weeks, PFS, and OS - To assess the safety and tolerability of oral PF-02341066 - To determine PK in this patient population using 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 changes from baseline in expression of biomarkers in signaling pathways (including JAK/STAT, MEK/ERK, and PI3K/AKT pathways) to pharmacokinetic and outcome measures - To assess PRO of HRQoL, disease/treatment-related symptoms of lung cancer, and general health status |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial: 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. Meets one of the following criteria: •Randomized to Arm B (pemetrexed or docetaxel) of Study A8081007 and was discontinued from treatment due to RECIST version 1.1-defined progression of disease as determined by independent radiology review •Ineligibility for A8081007 due to (1) prior treatment for advanced disease with more than one chemotherapy regimen, (2) prior treatment with only one chemotherapy regimen for advanced disease and that regimen was not platinum-based, (3) prior treatment with pemetrexed as part of their platinum-based chemotherapy and did not meet the docetaxel eligibility requirements from Protocol A8081007 or (4) treated with docetaxel as part of their platinum-based prior chemotherapy but have NSCLC that is predominantly squamous cell carcinoma and thus, not eligible to be dosed with pemetrexed. 4. Patients with brain metastases are eligible if appropriately treated and neurologically stable for at least 2 weeks and are not taking any medications contraindicated in Exclusion Criteria #11-13 5. Any prior treatment (chemotherapy, radiation or surgery) must have been completed at least 2 weeks prior to initiation of study medication. Any acute toxicity must have been recovered to ≤ Grade 1 (except alopecia) 6. Tumors must have measurable disease as per RECIST (version 1.1) (see Appendix 6) 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 •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 (except patients with documented Gilbert’s syndrome) •Absolute neutrophil count (ANC) ≥1500/µL •Platelets ≥100,000/µL •Hemoglobin ≥9.0 g/dL •Serum creatinine ≤1.5 x ULN 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 11. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures including completion of the PRO measures. |
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E.4 | Principal exclusion criteria |
Patients presenting with any of the following will not be included in the trial: 1. Eligibility for Protocol A8081007 2. No prior chemotherapy for advanced NSCLC, or erlotinib or gefitinib as the only prior treatment for advanced NSCLC 3. Current treatment on another therapeutic clinical trial 4. Prior therapy specifically directed against ALK 5. Spinal cord compression, carcinomatous meningitis, or leptomeningeal disease. 6. 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 7. Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade, or QTc interval >470 msec 8. Previous treatment with PF-02341066 9. Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy) 10. Pregnancy or breastfeeding. 11. 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 12. 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. 13. Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to aripiprazole, ergotamine, halofantrine, pimozide, triazolam, astemizole*, cisapride*, and terfenadine* (* withdrawn from U.S. market) 14. 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 15. 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint: ORR Secondary Endpoints: DR, DCR at 6 and 12 weeks, PFS, OS Type, incidence, severity, seriousness and relationship to study medications of adverse events (AE) and any laboratory abnormalities Plasma concentrations of PF-02341066 Types of EML4-ALK fusion variants and ALK protein expression Protein expression of identified biomarkers in serial tumor samples from surgery or biopsy, when available HRQoL, lung cancer specific symptoms, and general health status |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
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 | No |
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) | No |
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 | 9 |
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 |
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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
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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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |