A Double Blind Placebo Controlled Randomized Trial of PF-804 in Patients With Incurable Stage IIIB/IV Non-Small Cell Lung Cancer After Failure of Standard Therapy for Advanced or Metastatic Disease
- Conditions
- -C34 Malignant neoplasm of bronchus and lungMalignant neoplasm of bronchus and lungC34
- Registration Number
- PER-147-09
- Lead Sponsor
- PFIZER S.A., National Cancer Institute of Canada - Clinical Trials Group (NCIC CTG),
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 0
• Histologically confirmed diagnosis of non-small cell lung carcinoma. Patients must have an adequate sample either histopathological or cytological (see Section 13), they must give their consent to deliver all samples for this protocol, and the center / pathologist must have agreed to send the samples.
• Patients must have evidence of illness, but it is not mandatory that it be measurable disease. In order to be considered evaluable for a full or partial response evaluation, patients must have at least one measurable lesion, as follows: X-ray> 20 mm Helical CT scan or physical examination> 10 mm (lymph nodes must be> 15 mm in the short axis Measurable lesions should be outside a previous radiotherapy field, if they are the only site of the disease, unless the disease progression has been documented.
• Male or female gender, 18 years of age or older.
• ECOG functional status of 0,1,2 or 3 (see Appendix ü). Patients with a functional status of 3 are eligible on condition that the researcher guarantees that the patient has a reasonable life expectancy (> 6 weeks).
• The patient can (that is, fluently enough) and is willing to complete the quality of life questionnaires. The baseline evaluation must have been completed. The inability (illiteracy, loss of vision or other equivalent reason) to complete the questionnaires will not be an impediment to the patient´s eligibility for the study. However, even if they have the capacity, the lack of willingness to complete the questionnaires will mean that the patient cannot be chosen for the study.
• Patient consent must be obtained, in accordance with the requirements of local Institutional Committees and / or Committees of the University of Human Experimentation. It will be the responsibility of the participating local researchers to obtain the necessary local authorization, as well as to indicate in writing to the NCIC CTTCG Study Coordinator that such authorization was obtained, before the study begins at that center. Due to different criteria requirements, a standard consent form for the study will not be provided, but a sample form is provided in Appendix IX. A copy of the total initial approval of the Board of the Institutional Review Committee and the approved consent form must be sent to the central office. The patient must sign the consent form before randomization or registration. Please note that the consent form for this study must include a statement authorizing NCIC CTG and control agencies to inspect and review patient records and medical records (see Section N.® 16 for more details ).
• Patients should facilitate access for treatment and follow-up. All randomized patients should be followed up and treated in the participating centers. Researchers should ensure that randomized patients in this study are available to fully document treatment, adverse events and follow-up.
• In accordance with the NCIC CTG policy, treatment according to the protocol must begin within 2 business days of the patient´s randomization.
• Patients who receive concurrent treatment with other experimental medications or anti-cancer therapy.
• Patients who had suffered untreated and / or uncontrolled cardiovascular conditions and / or had symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication administration, history of atrioventricular conduction defects of 2 and 3. grade). Patients with significant cardiac history, even when controlled, should have LVEF> 50%
• Patients with untreated brain or meningeal metastases. (CT scans are not required to rule out this, unless there is a clinical assumption of disease in the CNS). Patients with disease in the treated CNS are eligible, with radiological or clinical evidence of stable brain metastases, without evidence of cavitation or hemorrhage in the brain injury, provided that it is asymptomatic and does not require the administration of corticosteroids (there should be steroid administration suspended at least 1 week before randomization).
• Patients with active or uncontrolled infections, or with serious illnesses or medical conditions that would not allow the patient to manage as established by the protocol,
• Medium QTc with Bazetts correction> 470msec in the selection ECG or family history of long QT syndrome.
• Medications that are highly dependent on CYP2D6 for metabolism are prohibited, since PF-804 is a potent CYP2D6 inhibitor in in vitro assays. These inhibitors or inducers are prohibited 7 days before the first dose until the end of treatment with PF-804. These include: Smetoprolol, propafenone, timolol, amitriptyline, clomipramine, desipramine, imipramine, paroxetine, haloperidol, risperidone, thioridazine, codeine, flecainide, mexiletine, tamoxifen, venlafaxine. Lidocaine may be used with clinical monitoring (including telemetry). Opioids such as morphine, oxycodone, dihydrocodeine, hydrocodone, and tramadol may be used as codeine substitutes. The use of these opioids for the alteration of analgesia should be monitored during treatment with PF-804, since they can be partially metabolized by CYP2D6. If PF-804 is administered with medications that are substrates of P-glycoprotein (P-gp) and that have a limited therapeutic index, monitoring for exaggerated effect and / or toxicities is recommended.
• Inappropriate pregnancy or contraception. Women should be postmenopausal, surgically sterile, or use two reliable forms of contraception. Women of childbearing age should have a pregnancy test and have a negative result within 7 days prior to randomization. Men must be surgically sterile or use a barrier method of contraception.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:It is defined as the time from randomization to death from any cause,<br>Measure:Overall Survival<br>Timepoints:42 Months<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:It is defined as the time from randomization to death from any cause,<br>Measure:Overall Survival in KRAS-WT Patients<br>Timepoints:42 Months<br>;<br>Outcome name:It is defined as the time from randomization to death from any cause,<br>Measure:Overall Survival in EGFR-mutant Patients<br>Timepoints:42 Months<br>;<br>Outcome name:progression were evaluated using the revised international criteria (1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumours) committee<br><br>Measure:Progression-free Survival<br>Timepoints:42 Months<br>;<br>Outcome name:Response were evaluated in this study using the revised international criteria (1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumours) committee. BEST RESPONSE from the start of study treatment until the end of treatment were reported.Objective response rate is the sum of CR + PR divided by the total number of patients in each group.<br><br>Measure:Objective Response Rate<br>Timepoints:42 months<br>