June 2009 Respiratory Committee CALGB 30610

Transcription

1 30610 Phase III comparison of thoracic radiotherapy regimens in patients with limited small cell lung cancer also receiving cisplatin and etoposide Activated: March 15, 2008 Study Chairpersons: J. Bogart Total Accrual as of 4/16/2009: 33 G. Masters Projected Accrual : 670 Statisticians: H. Pang Current Protocol Update: #1, December 15, 2008 L. Hodgson Data Coordinator: S. Sutherland SCHEMA (1 cycle = 21 days) Patients will receive 4 cycles of chemotherapy on all arms Prophylactic cranial irradiation (PCI) should be offered to all patients with a complete or near complete response Part II: Based on the results of Part I, the experimental arm with the higher rate of toxic events will be discontinued and patients will be randomized as follows: Prophylactic cranial irradiation (PCI) should be offered to all patients with a complete or near complete response. Respiratory - 27

2 Objectives Primary To determine whether administering high dose thoracic radiotherapy, 70 Gy (2 Gy once-daily over 7 weeks) or 61.2 Gy (1.8 Gy once daily for 16 days followed by 1.8 Gy twice daily for 9 days), will improve median and 2- year survival compared with 45 Gy (1.5 Gy twice daily over 3 weeks) in patients with limited stage small cell lung cancer. Secondary 1. To compare treatment related toxic effects of thoracic radiotherapy regimens in patients with limited stage small cell lung cancer. 2. To compare response rates, failure-free survival and toxicity of thoracic radiotherapy regimens in patients with limited stage small cell lung cancer. 3. To compare rates of local relapse, distant metastases and brain metastases with these regimens. 4. To compare patients quality of life between these treatment regimens in terms of their physical symptoms, physical functioning and psychological state. 5. To describe the patterns of use of thoracic intensity modulated radiation therapy (IMRT) in patients with limited stage small cell lung cancer. 6. To examine blood-based biomarkers of response and resistance to cisplatin and etoposide. Eligibility Criteria Histologically or cytologically documented small cell lung cancer of limited stage Measurable disease No prior chemotherapy or radiotherapy for SCLC No prior mediastinal or thoracic radiotherapy Patients with complete surgical resection of disease are not eligible ECOG Performance Status 0-2 Non-pregnant and non-nursing Age 18 years Required Initial Laboratory Values Granulocytes Platelets AST( SGOT) Total Bilirubin Serum Creatinine OR Calculated CrCI 1,500/µl 100,000/µl < 2 x ULN <1.5 x ULN <1.5 x ULN 70 ml/min Administrative Comments CALGB was activated on March 15, As of April 16, 2009, there were 33 patients enrolled. After 30 patients are enrolled in each experiment arms, an interim endpoint will be utilized to select between the two experimental treatment arms, Arm B and Arm C. There were adverse event data for 24 patients. Accrual Accrual by Institution For Period 3/15/2008 through 4/16/2009 Main/At-Large Member Affiliate Total BATI CCHLTH CHAPEL CHICAGO GRENVIL MARYLAND MVCC NCRF OSUMC RPCI SECCC SYRACUSE WASH-BARN CALGB Total CTSU 18 Total Accrual 33 Accrual by Month Total Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Total Respiratory - 28

3 Adverse Events Hematologic Adverse Events Blood/Bone Marrow Respiratory - 29 Hemoglobin B 3 ( 25%) 0 ( 0%) 0 ( 0%) 12 Leukocytes (total WBC) A 0 ( 0%) 2 ( 33%) 0 ( 0%) 6 B 3 ( 25%) 4 ( 33%) 0 ( 0%) 12 C 3 ( 50%) 1 ( 17%) 0 ( 0%) 6 Lymphopenia A 0 ( 0%) 1 ( 17%) 0 ( 0%) 6 C 2 ( 33%) 1 ( 17%) 0 ( 0%) 6 Neutrophils/granulocytes (ANC/AGC) A 1 ( 17%) 2 ( 33%) 0 ( 0%) 6 B 3 ( 25%) 7 ( 58%) 0 ( 0%) 12 C 2 ( 33%) 2 ( 33%) 0 ( 0%) 6 Platelets A 0 ( 0%) 2 ( 33%) 0 ( 0%) 6 Maximum Hematologic AE A 1 ( 17%) 2 ( 33%) 0 ( 0%) 6 Non-Hematologic Adverse Events Auditory/Ear Hearing: patients without baseline audiogram B 2 ( 17%) 9 ( 75%) 0 ( 0%) 12 C 2 ( 33%) 4 ( 67%) 0 ( 0%) 6 Tinnitus Coagulation Prothrombin time (PT) Constitutional Symptoms Fatigue (asthenia, lethargy, malaise) B 2 ( 17%) 1 ( 8%) 0 ( 0%) 12 Fever (in the absence of neutropenia ) Gastrointestinal

4 Infection Anorexia Dehydration Dysphagia esophagitis odynophagia Dysphagia (difficulty swallowing) Esophagitis B 1 ( 8%) 1 ( 8%) 0 ( 0%) 12 Nausea Vomiting Infection (documented clinically or microbiol Infection/Febrile Febrile neutropenia (fever of unknown origin Metabolic/Laboratory ALT, SGPT (serum glutamic pyruvic transaminas AST, SGOT(serum glutamic oxaloacetic transami ) Albumin, serum-low (hypoalbuminemia) B 3 ( 25%) 0 ( 0%) 0 ( 0%) 12 A 1 ( 17%) 1 ( 17%) 0 ( 0%) 6 Calcium serum-low (hypocalcemia) Respiratory - 30

5 Hypokalemia Hyponatremia Hypophosphatemia A 0 ( 0%) 1 ( 17%) 0 ( 0%) 6 Musculoskeletal Muscle weakness, generalized or specific area Neurology Pain Dizziness Pain Renal/Genitourinary Vascular Renal failure Thrombosis/embolism (vascular access-related) Thrombosis/thrombus/embolism A 2 ( 33%) 0 ( 0%) 0 ( 0%) 6 Maximum Non-Hematologic AE A 4 ( 67%) 2 ( 33%) 0 ( 0%) 6 B 4 ( 33%) 2 ( 17%) 0 ( 0%) 12 C 3 ( 50%) 0 ( 0%) 0 ( 0%) 6 Maximum Overall AE A 4 ( 67%) 2 ( 33%) 0 ( 0%) 6 B 3 ( 25%) 9 ( 75%) 0 ( 0%) 12 C 2 ( 33%) 4 ( 67%) 0 ( 0%) 6 Respiratory - 31