Treatment of patients with locally advanced or metastatic non-small lung cancer (NSLC) after failure of one prior chemotherapy regimen for advanced disease MedDRA version: Med Level: VTc Classification code 10061873
Conditions
Sponsors
Pfizer Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) 2. Locally advanced or metastatic NSCLC not amenable to curative treatment 3. Measurable disease defined by at least one lesion that can be accurately measured in at least one dimension as =20 mm with conventional techniques or =10 mm with spiral CT scan within 28 days prior to treatment (RECIST criteria) 4. Prior treatment with platinum-based chemotherapy for advanced NSCLC 5. Evidence of progressive disease following prior platinum-based chemotherapy 6. Prior treatment with only one prior chemotherapy regimen (including adjuvant therapy) - Prior surgery and/or radiotherapy is permitted 7. Recovery from all acute toxic effects of prior chemotherapy, radiation therapy and surgery. The interval between completion of these treatments and enrollment into the trial should be at least 2 weeks 8. Males or females aged =18 years 9. ECOG performance status (PS) 0 or 1 10. Adequate organ function as determine by the following criteria: • Absolute neutrophil count (ANC) =1.5 x 10 000 000 000/L • Platelet count =100 x 10 000 000 000/L • Calculated creatinine clearance =45 mL/min using the standard Cockroft and Gault forrmula • AST (SGOT) and ALT (SGPT) =3 x ULN, in absence of liver metastasis; AST (SGOT) and ALT (SGPT) = 5 x ULN, in presence of liver metastases • Total bilirubin =1.25 x ULN 11. Female patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within the 72 hours prior to starting treatment. Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving study 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 12. Provide written, voluntary informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any histological/cytological evidence of small cell or carcinoid lung cancer 2. Uncontrolled pleural effusion [a controlled pleural effusion is defined as a basal effusion that is radiologically stable for at least 2 weeks]. In patients with clinically significant third space fluid, consideration should be given to draining the effusion prior to pemetrexed administration 3. Known central nervous system (CNS) metastasis - CNS imaging is not required at baseline for patients who have no symptoms suggestive of CNS metastases 4. Prior neoadjuvant or adjuvant chemotherapy for NSCLC 5. Previous radiotherapy to the only site of measurable disease 6. Any acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or study drug administration or could interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into the study. This includes but is not limited to: - Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren’s syndrome, autoimmune thrombocytopenia or glomerulonephritis - History of allogeneic transplant - Untreated and/or uncontrolled superior vena cava syndrome - Untreated and/or uncontrolled hypercalcemia - Requirement for chronic treatment with therapeutic doses of systemic corticosteroids. Use of steroid inhalers, or oral “physiologic replacement” doses of corticosteroids is permitted. Physiological replacement doses will be defined as =37.5 mg/day of cortisone, =7.5 mg/day of prednisolone or =1.0 mg/day of dexamethasone. Patients on other replacement regimens must be discussed with the sponsor - Requirement for chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) - Uncontrolled hypertension, unstable angina, myocardial infarction or symptomatic congestive heart failure within the past 12 months, or serious uncontrolled cardiac arrhythmia - Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV). Serological testing will not be required at baseline for patients who have no symptoms suggestive of infection - Pre-existing peripheral neuropathy > CTCAE Grade 2 - Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent or compliance with the requirements of the protocol 7. History of any active malignancy (other than NSCLC) during the last 3 years except non-melanoma skin cancer, in situ cervical cancer, or cured, early prostate cancer in a patient with PSA level < ULN 8. Prior treatment with pemetrexed or PF-3512676 or prior enrollment in another PF-3512676 trial 9. Known or suspected hypersensitivity to either of the study drugs (pemetrexed or PF 3512676), study drug classes (antifolates, ODNs) or excipients in the formulation of study drugs 10. Female patients who are pregnant or nursing 11. Inability or lack of willingness to comply with scheduled visits, therapy plans or laboratory tests 12. Current enrollment in another therapeutic clinical trial 13. Use of any investigational agent in the past 4 weeks.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To assess Progression Free Survival (PFS) in patients randomized to pemetrexed plus PF-3512676 (Investigational Treatment) and in patients randomized to pemetrexed alone (Control Treatment Arm).;Secondary Objective: -To assess secondary measures of efficacy for PF-3512676 administered in combination with pemetrexed - To assess the safety and tolerability of PF-3512676 administered in combination with pemetrexed - To assess the health-related quality of life and disease/treatment related symptoms of patients treated with PF-3512676 in combination with pemetrexed - To assess the effect of PF-3512676 on the pharmacokinetics of pemetrexed - To assess the pharmacokinetics of PF-3512676 when administered in combination with pemetrexed - To determine germline TLR-9 genotype, and explore the association between genotype and measurements of efficacy and safety. ;Primary end point(s): Primary Endpoint: - Progression free survival (PFS) defined as the time from randomization to the date of progression or death due any cause, whichever occurs first. Secondary Endpoints: - Time to tumor progression (TTP) defined as the time from randomization to the date of progression. - Overall confirmed objective response rate (ORR), defined as the proportion of patients with a confirmed best response characterized as either a complete response (CR) or partial response (PR) (target lesions and tumor response defined according to RECIST guidelines). Confirmed responses are those that persist on a follow-up imaging assessment =4 weeks after the initial objective documentation of response. - Duration of response (DR) defined as the time from first documentation of response to the date of progression. - Overall survival (OS) defined as the time from randomization to the date of death due to any cause. - Overall safety profile characterized by type, frequency, severity and relationship to study therapy of adverse events and laboratory abnormalities. - Patient Rep | — |
Countries
Germany, Italy
Outcome results
None listed