Research Study Summary
A Phase 2, Multi-Cohort Study to Evaluate the Impact of Prophylactic Intervention on Dermatologic and Gastrointestinal Adverse Events and Patient Reported Outcomes in Patients Treated with Dacomitinib (PF-00299804)
Patient Inclusion Criteria:
Patients must meet all of the following inclusion criteria to be eligible for enrollment into this study:
- Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study;
- Patients who are willing and able to comply with study scheduled visits, treatment plan, laboratory tests, and other study procedures including PRO measures and compliance with prophylactic (preemptive) treatment;
- Age =18 years, male or female;
- Evidence of histopathologically confirmed advanced (Stage IIIB/IV) NSCLC for which there is no curative standard therapy in the judgment of the investigator:
- Cohort I and Cohort II:
Patients who received at least one prior regimen of systemic therapy which includes at least one standard chemotherapy for advanced NSCLC
- Cohort III:
Patients with known EGFR (HER-1) mutation, HER-2 mutation or HER-2 amplification (amplification defined as a HER-2 gene/centromere of chromosome 17 ratio of ??2; the minimum number of nuclei required to calculate the ratio is at least 50). No prior treatment with systemic chemotherapy for advanced disease (Stage IIIB/IV). Prior adjuvant chemotherapy for Stage I-III or combined modality chemotherapy-radiation for Stage IIIA disease is allowed if treatment completed >12 months prior to enrollment/randomization.
- No prior EGFR-targeted or HER-targeted therapy is allowed;
- Patients must have evidence of disease; however, measurable disease is not mandatory. Patients with non-measurable disease only (for example, radiographically visualized lesions not to be measurable by standard criteria, pleural or pericardial effusions, ascites, bone-only disease, lymphangitic involvement of the lung, palpable lesions that cannot be accurately measured with calipers, and abdominal masses identified on clinical exam that are not measurable by reproducible imaging techniques) are allowed to enroll;
- Brain metastases treated with radiation or surgery are allowed if the patient is
radiologically and neurologically stable and the patient is off corticosteroids for at least 2 weeks prior to enrollment/randomization;
- . ECOG Performance Status of 0, 1 and 2;
- Any prior treatment (chemotherapy, radiation or surgery) must have been completed at least 2 weeks prior to enrollment/randomization. Any acute toxicity related to prior therapy must have been recovered to Grade 1 (per NCI CTCAE v4) or baseline;
- Adequate Renal Function, including:
- Calculated estimated creatinine clearance =15 mL/min (as determined by site’s standard formula);
- No known history of renal papillary necrosis or pyelonephritis.
- Adequate Liver Function, including:
- Bilirubin (total) =1.5 x upper limit of normal (ULN);
- AST (SGOT) =2.5 x ULN (=5.0 x ULN if hepatic metastases present);
- ALT (SGPT) =2.5 x ULN (=5.0 x ULN if hepatic metastases present).
- . Female patients or their partners must be surgically sterile or be postmenopausal (defined as 12 months of amenorrhea following last menses), or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Where advised by investigator, double barrier contraception is defined as condom plus spermicide in combination with a female condom, diaphragm, cervical cap or intrauterine device.
- All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within 72 hours prior to starting treatment.
- Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving trial treatment and for at least 3 months thereafter. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
Patient Exclusion Criteria:Patients with known leptomeningeal metastases or symptomatic brain metastases.
Patients with previously diagnosed brain metastases for which treatment (radiation or surgery) is recommended in the judgment of the investigator are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 2 weeks, and are neurologically stable;
Chemotherapy, radiotherapy, biological or investigational agents within 2 weeks of baseline disease assessments;
Prior therapy with an agent that is known or proposed to be active by action on: EGFR tyrosine kinase or other HER family proteins including but not limited to erlotinib (Tarceva®), gefitinib (Iressa®), lapatinib (Tykerb®), cetuximab (Erbitux®), panitumumab (Vectibix®), trastuzumab (Herceptin®), ZD6474 (Zactima®), cantertinib (CI-1033), neratinib (HKI-272), Tovok (BIBW-2992), XL-647, AEE788, matuzumab and pertuzumab;
Investigational therapy as only treatment for advanced NSCLC without administration of an approved chemotherapy for advanced NSCLC (for Cohort I and Cohort II);
Any surgery (not including minor procedures such as lymph node biopsy) within 2 weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures;
Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medication;
Current enrollment in another therapeutic clinical trial;
Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this study;
Patients with known diffuse interstitial lung disease;
Uncontrolled or significant cardiovascular disease, including:
Patients presenting with any of the following will not be included in the study:
Prior malignancy: Patients will not be eligible if they have evidence of other malignancy (other than non-melanoma skin cancer or in-situ cervical cancer, or localized and presumed cured prostate cancer with Prostate Specific Antigen (PSA)
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 patient inappropriate for entry into this study;
Patients who are investigational site staff members or relatives of those site staff members or patients who are Pfizer employees directly involved in the conduct of the study;
Dacomitinib is a potent CYP2D6 inhibitor. A description of CYP2D6 metabolized drugs is provided in Section 5.6 and includes prohibited medications as well as medications for which the dose may need to be adjusted and close monitoring is necessary or recommended.
Pregnant females; breastfeeding females; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 3 months after last dose of investigational product. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate.
- Myocardial infarction within 12 months;
- Uncontrolled angina within 6 months;
- Congestive heart failure within 6 months;
- Diagnosed or suspected congenital long QT syndrome;
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation or Torsades de pointes);
- Prolonged QTc interval on pre-entry electrocardiogram. QTc must be less than CTC Grade 2 (=480 msec) using Fridericia’s correction formula with manual read by investigator if required. The ECG may be repeated for evaluation of eligibility after management of correctable causes for observed QTc prolongation;
- Any history of second or third degree heart block (may be eligible if currently have a pacemaker);
- Heart rate <50 beats per minute on baseline ECG;
- Uncontrolled hypertension.
To Learn more
CW ID: 180069
Date Last Changed:
November 12, 2013
Clinical Trial Snapshot
- Both Male and Female
- 18 and up
- Overall Status
- Facility Type
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