A randomized, double blind, phase 3 study of PF-00299804 versus erlotinib in the treatment of advanced non-small cell lung cancer

• Conditions: on-small cell lung cancer; MedDRA version: 13.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-022656-22-ES
• Lead Sponsor: Pfizer, S.L.U.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-06-16
• Last Update Posted: 12 October 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 800

Inclusion Criteria

1.Provision of a voluntarily given, personally signed, and dated written informed consent document;
2.Age >=18 years, male or female;
3.Evidence of pathologically confirmed, advanced NSCLC for which there is no curative standard therapy;
a.For the purpose of randomization/ stratification, the histologic subtype of NSCLC must be documented, preferably by WHO/ International Association for Study of Lung Cancer Histologic Classification of Lung Cancer criteria;
b.The diagnosis of NSCLC NOS (not otherwise specified) will not be sufficient for enrollment and randomization/stratification.
4.Specimen from archival or recently obtained tumor tissue is required, and will be sent to the Sponsor designated central laboratory for molecular testing of tumor tissue, including KRAS mutation status, and HER family testing (as available tissue allows).
5.ECOG 0-2 performance status;
6.Prior treatment with at least one and no more than two regimens of systemic therapy which include at least one standard chemotherapy for advanced NSCLC. For the purpose of this study the following convention regarding the counting of prior therapy regimen will be followed:
•Prior systemic adjuvant therapy or combined modality chemoradiation for locally advanced disease will not be counted against the total of 1 or 2 allowed prior regimens for advanced NSCLC if treatment was completed more than 12 months prior to ramdomization.
•Administration of a new agent upon completion of 4 6 cycles of platin based therapy but prior to documentation of progressive NSCLC is considered an additional regimen.
•Discontinuation of any systemic anti cancer drug due to intolerance (without documentation of progression of NSCLC) following administration of at least one full dose will count as one regimen.
•Substitution of one component of a combination drug regimen following administration of at least one full dose of the agent is considered the start of a new regimen (with the exception of substitution of the platin component of a cisplatin or carboplatin doublet).
•Prior investigational therapy in combination with a standard chemotherapy for NSCLC is counted as one regimen of systemic therapy;
7.Any prior treatment (chemotherapy, radiation or surgery) must have been completed at least 2 weeks prior to randomization. Any acute toxicity related to prior therapy must have been recovered to Grade 1 (per NCI CTCAE v4) or baseline;
8.Radiologically measurable disease by RECIST v1.1 criteria:
9.Brain metastases treated with radiation or surgery are allowed if radiologically and neurologically stable and the subject is off corticosteroids for at least 2 weeks prior to randomization;
10.Adequate Renal Function, including:
a.Estimated creatinine clearance >=15 mL/min (as determined by site’s standard formula);
b.No known history of renal papillary necrosis or pyelonephritis.
11.Adequate Liver Function, including:
•Bilirubin <=1.5 x upper limit of normal (ULN);
•AST (SGOT) <=2.5 x ULN (<=5.0 x ULN if hepatic metastases);
•ALT (SGPT) <=2.5 x ULN (<=5.0 x ULN if hepatic metastases).
12.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.
13.All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within 72 hours prior to st

Exclusion Criteria

1.Any evidence of mixed histology that includes elements of small cell or carcinoid lung cancer.
2.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 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.
3.Chemotherapy, radiotherapy (other than palliative radiotherapy to lesions that will not be followed for tumor assessment on this study, ie, non target lesions), biological or investigational agents within 2 weeks of baseline disease assessments.
4.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.
5.Investigational therapy as only treatment for advanced NSCLC, without administration of an approved chemotherapy for advanced NSCLC.
6.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.
7.Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug, such as the inability to take oral medication.
8.Current enrollment in another therapeutic clinical trial.
9.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.
10.Patients with known diffuse interstitial lung disease.
11.Uncontrolled or significant cardiovascular disease, including:
a.Myocardial infarction within 12 months;
b.Uncontrolled angina within 6 months;
c.Congestive heart failure within 6 months;
d.Diagnosed or suspected congenital long QT syndrome;
e.Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);
f.Prolonged QTc interval on pre entry electrocardiogram. QTc must be less than CTC Grade 2 (=480 msec) using Fredricia’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;
g.Any history of second or third degree heart block (may be eligible if currently have a pacemaker);
h.Heart rate <50/minute on baseline electrocardiogram;
i.Uncontrolled hypertension.
12.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) < ULN) within the last 3 years.
13.Other severe acute or chronic medical condition that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the in

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified