Non-Small Cell Lung Cancer

Transcription

1 Non-Small Cell Lung Cancer Title: A Phase III Randomized Trial of Adjuvant Chemotherapy With or Without Bevacizumab for Patients With Completely Resected Stage 1B (> 4 cm) - IIIA Non-Small Cell Lung Cancer (NSCLC) (ECOG E1505) Purpose: To evaluate overall survival with chemotherapy with or without bevacizumab used in the adjuvant setting in patients with resected stage IB (equal to or greater than 4 cm) - IIIA NSCLC> To evaluate disease free survival and toxicity with chemotherapy with or without bevacizumab used in the adjuvant setting in patients with resected stage IB (equal to or greater than 4 cm) - IIIA NSCLC. To perform analyses of tissue and blood to establish factors that predict for clinical outcome in patients receiving chemotherapy, with or without bevacizumab, for resected early stage NSCLC. To determine whether smoking status is linked to outcome for patients with resected stage IB (equal to or greater than 4 cm) - IIIA NSCLC treated with chemotherapy with or without bevacizumab in the adjuvant setting. Eligibility: In order to be eligible for this trial, patients must have undergone complete resection of their non-small cell lung cancer (NSCLC) [stage IB (> 4 cm)] [IIIA (T2-3N0, T1-3N1, T1-3N2] prior to enrollment. Accepted types of resection will consist of lobectomy, sleeve lobectomy, bi-lobectomy or pneumonectomy. Resections by segmentectomy or wedge resection will not be accepted. Mediastinal lymph node sampling at specified levels is required pre-operatively (mediastinoscopy) or intraoperatively (level 7 and 4 for right sided tumors or level 7 and 5 and/or 6 for left sided tumors). -If patient s tumor is stage IB, it must be > 4 cm in size. -Patients must be no less than 6 weeks (42 days) and no more than 12 weeks (84 days) post-thoracotomy at the time of randomization and must be adequately recovered from surgery. -Age > 18 years. -ECOG performance status 0 or 1. -Patients must not have received the following: -Prior systemic chemotherapy at any time. Methotrexate (MTX) given in low doses for non-malignant conditions with last dose at least 2 weeks prior to date of registration will be allowed. Other low dose chemotherapeutics for non-malignant conditions will be considered, but review by the study chair is required. -Hormonal cancer therapy or radiation therapy as prior cancer treatment within 5 years of randomization. (Prior surgery, biologic therapy, hormonal therapy, or radiation therapy for a malignancy over 5 years prior to enrollment that is now considered cured is acceptable.) -Patients must not have any history of cancer within 5 years from randomization, with the exception of in-situ carcinoma of the cervix or completely resected non-melanoma skin cancer. -Required laboratory values obtained within two weeks of randomization: ANC >?1500 mm3 Platelets >?100,000/mm3 Prothrombin time/inr >?1.5 Or, if patient is on therapeutic anticoagulation, prothrombin time/inr < 3.0 PTT >?institutional upper limit of normal (ULN) OR, if patient is on therapeutic anticoagulation, PTT must be < 1.5 x ULN. Total Bilirubin >?1.5 mg/dl SGOT (AST) < 5 x upper limit of normal (ULN): SGPT (ALT) < 5 x upper limit of normal (ULN): -Patients must have adequate renal function as determined by the following tests within 2 weeks prior to randomization: Serum Creatinine >?1.5 x institutional upper limit of normal (ULN) Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio. For UPC ratio > 0.5, 24-hour urine protein must be obtained and the level must be < 1000 mg for patient enrollment. NOTE: UPC ratio of spot urine is an estimation of the 24 urine protein excretion a UPC ratio of 1 is roughly equivalent to a

2 24-hour urine protein of 1 g. UPC ratio is calculated using one of the following formulas: [urine protein]/[urine creatinine] if both protein and creatinine are reported in mg/dl [(urine protein) x 0.088]/[urine creatinine] if urine creatinine is reported in mmol/l -Patients with a known history of myocardial infarction or other evidence of arterial thrombotic disease (angina) will be allowed on study only if they have had no evidence of active disease for at least 12 months prior to randomization. -Patients with any history of cerebral vascular accident (CVA) or transient ischemic attack (TIA) will not be allowed on trial. -Women must not be pregnant or breast-feeding due to potential harm to the fetus or infant from cytotoxic chemotherapy and the unknown risk from bevacizumab. It is also unknown if these agents are excreted into breast milk. All females of childbearing potential must have a blood or urine test within 2 weeks prior to randomization to rule out pregnancy. -Both fertile men and women must agree to use adequate contraceptive measures during study treatment and for at least 6 months after completion of bevacizumab. -Patients must not have any clinically significant ongoing, active or serious infection, symptomatic or uncontrolled congestive heart failure, symptomatic or uncontrolled cardiac arrhythmia or any other medical condition or psychiatric illness/social situations that would limit compliance with study requirements. -Patients must have no history of bleeding diathesis or coagulopathy. -All patients must have a documented BP with systolic < 150 and diastolic < 90 within 28 days of registration. Patients with known hypertension must be on a stable regimen of antihypertensive therapy. -Patients receiving daily treatment with aspirin or non-steroidal anti-inflammatory agents (NSAIDS) are eligible. Treatment with dipyridamole (Persantine), ticlopine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal) is not allowed. Patients must have stopped taking any of these agents at least 7 days prior to randomization. -Patients must not have serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization OR core biopsy within 7 days prior to randomization. -Patients must not have a history of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to randomization. -Patients must not have any anticipated major surgical procedure(s) during the course of the study. -Patients must not have known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies. -Patients may be on a stable regimen of therapeutic anticoagulation or may be receiving prophylactic anticoagulation of venous access devices, provided that coagulation studies meet entry criteria 3.8. Caution must be exercised for patients requiring anticoagulation, including treatment with low dose heparin or low molecular weight heparin for DVT prophylaxis while on study due to an increased risk of bleeding with bevacizumab. -Patients with ongoing post-operative hemoptysis (defined as bright red blood of ½ teaspoon or more) are not eligible. Patients with pre-operative hemoptysis that has resolved postoperatively are eligible. -Pemetrexed/Cisplatin Therapy Patients who will receive pemetrexed/cisplatin therapy must meet all eligibility criteria ( ) as well as and Patients assigned to pemetrexed/cisplatin therapy must NOT have squamous cell histology.

3 Principal Investigator: Martinez, Roberto Approved Enrollment Number: 15 Non-Small Cell Lung Cancer Title: CALGB 30801: A Randomized Phase III Double Blind Trial Evaluating Selective COX-2 Inhibition in COX-2 Expressing Advanced Non-Small Cell Lung Cancer. Purpose: To confirm the beneficial effect of COX-2 inhibition in patients who have NSCLC that expresses COX-2. The primary endpoint is to demonstrate improvement in progression-free survival in patients with a COX-2 index equal to or greater than 4 with an estimated hazard ratio of 0.6. To describe the response rate, as well as the distribution of progression free survival and overall survival. To compare progression free survival between treatment arms for patients with COX-2 equal to or greater than 2. The comparison will also be made adjusting for CYP2C9 genotype and celecoxib trough concentrations as covariates. To correlate urinary PGE-M level with COX-2 expression. COX-2 inhibition and outcome. To evaluate the association between the -765G/C polymorphism in PTGS2 and COX-2 expression in non-small cell lung cancer specimens. Principal Investigator: Martinez, Roberto Approved Enrollment Number: 15

4 Non-Small Cell Lung Cancer Title: Amgen Protocol : A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Long-term Safety and Efficacy of Darbepoetin Alfa Administered at 500 µg Once-Every-3-Weeks in Anemic Subjects with Advanced Stage Nonsmall Cell Lung Cancer Receiving Multi-cycle Chemotherapy. Purpose: To determine the safety of darbepoetin alfa, including effects on survival and cancer progression, as well as the need for blood transfusions. Eligibility: Inclusion Criteria Disease Related -Subjects with stage IV NSCLC (not recurrent or re-staged) -Expected to receive at least 2 additional cycles (at least 6 total weeks) of first line myelosuppressive cyclic chemotherapy after randomization. Subjects should not be expected to receive only maintenance chemotherapy. -18 years of age or older at screening - Life expectancy > 6 months based on the judgment of the investigator and documented during screening Laboratory - Hemoglobin level 11.0 g/dl as assessed by the local laboratory; sample obtained within 7 days prior to randomization (retest in screening is acceptable) - Adequate serum folate ( 2 ng/ml) and vitamin B12 ( 200 pg/ml) levels assessed by central laboratory (supplementation and retest acceptable) during screening Imaging - Subjects must have had a baseline scan (CT, MRI, or PET/CT) of the chest to assess disease burden before starting on first line chemotherapy for NSCLC and those images must have been reviewed by the investigator prior to randomization. If the scan was performed more than 28 days prior to randomization, an additional scan must be performed and reviewed by the investigator to confirm that the patient has not progressed before randomization. Exclusion Criteria Disease Related - Known primary benign or malignant hematologic disorder which can cause anemia -History of, or current active cancer other than NSCLC, with the exception of curatively resected non-melanomatous skin cancer, curatively treated cervical carcinoma in situ, or other primary solid tumors curatively treated with no known active disease present and no curative treatment administered for the last 3 years -Received any prior adjuvant or neoadjuvant therapy for NSCLC -Subjects with a history of brain metastasis -Uncontrolled hypertension (systolic BP > 160 mmhg or diastolic BP > 100 mmhg), or as determined by the investigator during screening -History of neutralizing antibody activity to rhuepo or darbepoetin alfa - Uncontrolled angina, uncontrolled heart failure, or uncontrolled cardiac arrhythmia as determined by the investigator at screening. Subjects with known myocardial infarction within 6 months prior to randomization. -Subjects with a history of seizure disorder taking anti-seizure medication within 30 days prior to randomization

5 Principal Investigator: Martinez, Roberto Approved Enrollment Number: 5 -Clinically significant systemic infection or uncontrolled chronic inflammatory disease (eg, rheumatoid arthritis, inflammatory bowel disease) as determined by the investigator during screening -Known seropositivity for HIV or diagnosis of AIDS, positive for hepatitis B surface antigen, or seropositive for hepatitis C virus - History of pure red cell aplasia -History of deep venous thrombosis or embolic event (eg, pulmonary embolism) within 6 months prior to randomization Laboratory - Transferrin saturation < 20% and ferritin < 50 ng/ml as assessed by the central laboratory during screening. Subjects must have both to be excluded (supplementation and retest acceptable). -Abnormal renal function (serum creatinine level > 2X ULN) as assessed by the central laboratory during screening -Abnormal liver function (total bilirubin > 2X ULN or liver enzymes ALT or AST > 2.5X ULN for subjects without liver metastasis or 5X ULN for subjects with liver metastasis) as assessed by the central laboratory during screening. Subjects with documented Gilbert s Disease may be eligible. Medications -Received any RBC transfusion within 28 days prior to randomization. -Plan to receive any RBC transfusion between randomization and study day 1 Known previous treatment failure to ESAs (eg, rhuepo, darbepoetin alfa) -ESA therapy within the 28 days prior to randomization -Known hypersensitivity to recombinant ESAs or the excipients contained within the investigational product General -Less than 30 days since receipt of any investigational product or device. Investigational use/receipt of a medicinal product or device that has been approved by the country s local regulatory authority for any indication is permitted -Subjects of reproductive potential who are pregnant, breast feeding or not willing to use effective contraceptive precautions during the study and for at least one month after the last dose of investigational product in the judgment of the investigator (including females of childbearing potential who are partners of male subjects)