NCCTG Status Report for Study N September 2007

Transcription

1 Phase I/II Study of Concurrent Chemotherapy and Escalating Doses 3-D Conformal Radiotherapy (RT) Followed by Three Cycles of Chemotherapy for Unresectable Non-Small Cell Lung Cancer (NSCLC) Using a New RT Paradigm Purpose of Study: 1) Part 1 - To identify the MTD of RT using 3-D treatment planning, no prohylactic nodal RT and concurrent chemotherapy for unresectable NSCLC. 2) Part 2 - Primary: To assess 2-year survival 3) Part 2 - Secondary: To assess progression-free local control rate, tolerability, and QOL as measured by the Lung Cancer Symptom Scale. Study Chairs: Steven E. Schild M.D. William L. McGinnis M.D. QC Specialist: Jennifer P Schreiber Statistician: Shauna L Hillman M.S. Nurse Resource: Wanda L. DeKrey R.N., OCN Status: 05/17/2002 Activated Projected Number of Patients: 84 Excluded: None Final Accrual: NA Stratification Phase I pts not receiving RT at MTD vs Phase I pts receiving RT at MTD and Factors: Phase II pts Schema: Part 1: to determine MTD of radiation therapy (RT) Register CBDCA + TAXOL + escalating doses of RT Treating Schedule: Part 2: trial using MTD of RT determined from Part 1 Register CBDCA + TAXOL + RT 3-week break CBDCA + TAXOL Arm Agent Dose Route Days Freq * Taxol 50 mg/m2 IV over 1 hr in 250 ml NS 1 Q week while receiving RT or D5W * CBDCA AUC = 2 IV over 30 minutes after Taxol 1 Q week while receiving RT TAXOL 200 mg/m2 IV over 1 hour in 250 ml of NS or D5W CBDCA AUC = 6 IV over 30 min after TAXOL 1 Every 21 days x 3 cycles (starting 3 wks after RT complete) 1 Every 21 days x 3 cycles (starting 3 wks after RT complete) N Page 1 of 5

2 Arm Dose Days FX/Day FX/Size # FX RT Length + Phase I-assigned at registration + Phase II-determined by outcome of Phase I M-F Gy dependent on assigned dose M-F Gy determined by phase I results dependent on assigned dose determined by phase I results * Chemotherapy schedule is constant despite phase of study. If RT is suspended, chemo is suspended until RT is resumed. Chemo may be administered before or after RT. + RT begins day 1 of chemotherapy. Study Design: This trial was designed as a Phase I/II trial to determine a safe dose level for RT using 3D treatment planning and no prophylactic nodal RT in unresectable NSCLC, and to determine whether the regimen can improve the 2-year survival rate. The Phase II portion has a single-stage, 3-outcome study design with an interim analysis occurring after the first 19 patients have been enrolled. This regimen will be considered promising if 21 or more of the first 48 evaluable patients are alive at 2 years after registration. If 14 or fewer patients are alive at 2 years, we will consider this regimen ineffective in this patient population. If between 15 and 20 patients are alive at 2 years post-registration, then we will consider other factors such as toxicity and time to progression to determine if this regimen is worth pursuring further. Patients receiving the MTD on Phase I will be included in the Phase II analysis. Accrual: When data was frozen for this report on August 6, 2007, twenty-six patients had been accrued (3 pts at dose level 1, 17 pts at dose level 2, and 6 pts at dose level 3). Two patients were replaced at dose level 3 since one patient went off treatment prior to receiving RT treatment and the other went off treatment for non-compliance issues, thus the two patients were not evaluable. See Accrual Table for more information. Patient Characteristics: The distribution of patient characteristics at study entry is located in the Baseline Characteristics Table. Adverse Events: Adverse event data are available on 25 patients. Grade 3+ events have been reported on 20 (80%) patients across all dose levels and 4 (16%) patients have reported a grade 4+. Three (12%) patients experienced grade 4+ non-hematologic adverse events: 1 patient at dose level 1 experienced grade 5 vomiting (not related) on observation four years after the end of treatment; 1 patient at dose level 3 experienced grade 4 thrombosis (not related) and a grade 5 infection with no neutropenia (possibly related); and 1 patient on dose level 2 experienced grade 4 dyspnea (probably related) and grade 5 pneumonitis (probably related). N Page 2 of 5

3 In the first cohort of 3 at dose level 1, there were no DLTs reported during the designated evaluation period. Therefore, the study was opened to dose level 2. In the first cohort of 3 at dose level 2, there were no DLTs reported during the designated evaluation period. Therefore, the study was opened to dose level 3. A late occurring DLT (grade 3 pneumonitis, definitely related) was reported. This event occurred 11 months after the end of study treatment. In the first cohort of 3 at dose level 3, there were no DLTs reported during the designated evaluation period. Therefore, the study was to enroll a second cohort of 3 at dose level 3. Two patients were replaced after one patient was deemed a cancel, and a second had an allergic reaction to Taxol and thus could not complete study treatment. A late occurring DLT (grade 3 pnemonitis, probably related) was reported. This event occurred more than 3 years after the end of study treatment. The first patient on the second cohort of 3 reported a DLT (grade 4 thrombosis and grade 5 infection w/o neutropenia) at the 3-month post RT visit; thus, dose de-escalation to dose level 2 was necessary. Per protocol, we evaluated 6 more patients at dose level 2 to further examine the toxicity. In the first 3 patients, no DLTs were reported. In the second 3 patients, one DLT was reported (grade 3 radiation pneumonitis, definitely related) and a grade 4 neutropenia was reported. It is unclear whether this grade 4 event is a DLT or not bcause labs were not done until day 6, but at day 6 the neutropenia was resolved (protocol required grade 4 neutropenia to last 5 days to be considered a DLT). To further define the potential risks of the treatment regimen and to evaluate the addition of three cycles of chemotherapy, we felt it necessary to enroll an additional 6 patients at dose level 2. We have enrolled the additional 6 in this cohort. Thus far, none of the six evaluable patients have reported DLTs. Study Status: The trial temporarily closed August 17, 2007 after enrolling an additional 6 patients at dose level 2 (74 Gy/37 fxs) in the Phase I portion of this study. These additional patients will be used to further define the potential risks of this treatment regimen. N Page 3 of 5

4 Accrual Table: NCCTG Status Report for Study N September 2007 Randomizing Membership Total Entered Past 6 Months Past 12 Months Des Moines Fargo Jacksonville Mayo Mo Valley Scottsdale Sioux Falls Toledo Total Membership Accrual Baseline Characteristics Table: Gender Characteristics f 7 m 19 Performance Score Race White 25 American Indian or Alaska Native 1 Smoking Status Never smoked 2 Former smoker 15 Current smoker 9 Stage I 4 II 1 IIIA 12 IIIB 9 Arm A N Page 4 of 5

5 Grade 4/5 and Most Frequent Adverse Event Table: Arm A Evaluable Patients: 25 Body System Adverse Event A R M Maximum Severity Per Patient Grade 1/2 Grade 3 Grade 4 Grade 5 N % N % N % N % Hematology NEUTROPENIA A LEUKOPENIA A ANEMIA A THROMBOCYTOPENIA A Allergy/Immunology HYPERSENSITIVITY A Cardiovascular HYPOTENSION A THROMBOSIS A EDEMA A Constitutional Symptoms FATIGUE A FEVER-NO ANC A WEIGHT LOSS A Dermatology/Skin ALOPECIA A RASH A DERMATITIS-RT A Gastrointestinal ANOREXIA A NAUSEA A STOMATITIS A DEHYDRATION A DYSPHASIA-ESOPH RT A CONSTIPATION A VOMITING A DIARRHEA-NO COLOSTOM A Hepatic ALK PHOS A Infection/Febrile Neutropenia INFECTION-NO ANC A Metabolic/Laboratory HYPONATREMIA A HYPOKALEMIA A HYPERGLYCEMIA A Neurology NEURO-SENSORY A NEURO-MOTOR A Pain HEADACHE A MYALGIA A Pulmonary COUGH A DYSPNEA A PNEUMONITIS A HYPOXIA A Maximum Grade Adverse Event A N Page 5 of 5