-02341066 and PF-00299804 for Advanced Non-Small Cell Lung Cancer

Stopped early · Phase 1

Conditions studied: Carcinoma, Non-Small Cell Lung, Adenocarcinoma, Carcinoma, Squamous Cell, Carcinoma, Large Cell

In brief

Background: \- PF-02341066 and PF-00299804 are drugs that specifically target certain proteins that may be more active in cancer cells than normal cells, in particular in non-small cell lung cancer. Both drugs seem to be able to stop the growth of or kill cancer cells. Researchers want to combine them to see if they are a safe and effective treatment for advanced non-small cell lung cancer. Objectives: \- To test the safety and effectiveness of PF-02341066 and PF-00299804 for advanced non-small cell lung cancer. Eligibility: \- Individuals at least 18 years of age with advanced non-small cell lung cancer that has not responded to standard treatments. Design: * Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, and imaging studies. Heart and lung function tests and an eye exam may also be given. * The first cycle of treatment will be 28 days. Every cycle after the first will be 21 days. Participants may have up to 17 cycles of treatment. * Participants will take both study drugs as tablets. Twelve hours after the first dose, participants will take only the PF-02341066. This dose schedule will remain the same throughout the study. * Participants will be monitored with frequent blood and urine tests and imaging studies. Tumor biopsies will be taken as needed. Those in the study will keep a diary to record any symptoms or side effects of taking the study drugs. * After 17 cycles of treatment, or after stopping the study drugs early for any other reason, participants will have a final followup visit.

Key facts

Study ID

NCT01441128

Run by

National Cancer Institute (NCI)

People needed

20

Starts

2011-09-01

Expected to finish

2015-02-26

Last updated by the study team

2019-12-17

Who can join

Age: 18 and older, up to 99. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Subjects presenting with any of the following will not be included in the study:
• Participation in other studies or treatment within 2 weeks before the current study begins and/or during study participation (with the exception of patients who are receiving single agent PF-00299804 and who enroll into Expansion Cohort 2 from ongoing trials including A7471017 and A7471028, and with the exception of patients being treated with single agent PF-02341066 treatment who enroll during the dose escalation phase and exercise the option of continuing single agent PF-02341066 treatment until the combination of PF-02341066 and PF-00299804 is given) to allow for recovery and drug wash-out.
• Known interstitial fibrosis or interstitial lung disease.
• Patients with known brain metastases who are neurologically stable (asymptomatic) for at least 2 weeks and with no ongoing requirement for corticosteroids may enroll on study before treatment of brain metastases.
• History of carcinomatous meningitis, or leptomeningeal disease.
• Any of the following within 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack.
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes). Diagnosed or suspected congenital long QT syndrome. Ongoing cardiac dysrhythmias of Grade greater than or equal to 2 (CTCAE version 4.02), uncontrolled atrial fibrillation of any grade, or QTc interval >470 msec.
• Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy).
• Patient must not have had major surgery or trauma within 28 days prior to enrollment.
• Active uncontrolled infection.
• Pregnant or lactating females.
• Significant gastrointestinal condition that may impair intake, transit, absorption or ability to tolerate investigational drugs.
• Prior malignancy (other than 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 3 years.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• Use of drugs or foods that are known potent CYP3A4 inhibitors within 7 days prior to the first dose of study medication, including but not limited to itraconazole, ketoconazole, miconazole, clarithromycin, erythromycin, indinavir, nefazodone, amprenavir, delavirdine, nelfinavir, ritonavir, saquinavir, diltiazem, verapamil and grapefruit juice.
• Use of drugs that are known potent CYP3A4 inducers within 12 days prior to the first dose of study medication, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifabutin, rifampin, tipranavir, ritonavir, and St. John s wort.
• Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine.
• Concurrent use of drug that are highly dependent on CYP2D6 metabolism including S-metoprolol, propafenone, timolol, amitriptyline, clomipramine, desipramine, imipramine, paroxetine, haloperidol, risperidone, thioridazine, codeine, flecainide, mexilletine, tamoxifen, venlafaxine.
• Dextromethorphan, a CYP2D6, substrate is allowed if medically indicated and no suitable alternative anti-tussive medication is available. However, the dose of dextromethorphan may need to be modified. In a clinical study in healthy volunteers who were extensive metabolizers (A7471039) PF-00299804 increased mean total exposure (AUC(last) and C(max)) of dextromethorphan 855% and 874%, respectively, following concomitant administration with PF-00299804 45 mg compared to exposure of administration of dextromethorphan alone. Extensive metabolizers comprise approximately 80% of the population, with ultra-, intermediate-, and poor-metabolizers accounting for the remaining portion of the general population. Therefore, if no alternative is available dextromethorphan dosing should be initiated at a lower dose (approx 25%) with close monitoring of patient clinical status. Dose increases or decreases of dextromethorphan may be considered based upon individual patient tolerability.
• Lidocaine may be used systemically with clinical monitoring (including telemetry).
• Opiates such as morphine, oxycodone, dihydrocodeine, hydrocodone, and tramadol can be used as substitutes to replace codeine. Use of these opiates should be monitored for altered analgesic effect during treatment as they may be partly metabolized by CYP2D6.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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