Phase Iii Randomized Trial Of Image-Guided Bone Marrow-Sparing Intensity Modulated Radiation Therapy (Ig-Bms-Imrt) For Locoregionally Advanced Cervical Cancer: The Intertecc-3 Trial.

TPS5600 Background: Cervical cancer is a leading cause of cancer death in women worldwide. Image-guided bone marrow-sparing intensity modulated radiation therapy (IG-BMS-IMRT) has shown potential to reduce acute toxicity of chemoradiotherapy and improve chemotherapy delivery in phase I and II trials (Mell LK, Sirák I, Wei L, et al. Bone Marrow-sparing IMRT With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2). Int J Radiat Oncol Biol Phys 2017;97:536-545. Mell LK, Saenz CC, Yashar CM, et al. Phase I Trial of Bone Marrow Sparing IMRT With Concurrent Cisplatin and Gemcitabine in Stage IB-IVA Cervical Cancer (abstr.) Int J Radiat Oncol Biol Phys 2016; 96: S14.). Methods: INTERTECC-3 is a randomized phase III trial designed to test the effect of IG-BMS-IMRT on progression-free survival (PFS) for women with unresected FIGO stage IB-IVA cervical carcinoma (clinicaltrials.gov #NCT01554397). It presently involves centers in the U.S., Czech Republic, U.K., India, Japan, and China. Women are randomized 3:2 to either (A) IG-BMS-IMRT or (B) standard chemoradiation, with 6 cycles of concurrent cisplatin (40 mg/m 2 ) weekly in both arms. Secondary objectives are to compare overall survival, treatment-related toxicity, disease recurrence, quality of life, chemotherapy delivery, and radiation quality assurance. Planning objectives require maintaining pelvic marrow and active marrow mean doses < 27 Gy and < 28.5 Gy respectively. Correlative studies involve longitudinal collection of magnetic resonance restriction spectrum imaging and 18 F-fluorothydimine positron emission tomography scans to assess imaging biomarkers of treatment response in select patients. 415 women will be enrolled to determine if IG-BMS-IMRT improves the median PFS from 3.2 to 5.0 years with 80% power and alpha = 0.05. INTERTECC-3 opened in the U.S. and Czech Republic in 2016. To date, 17 patients have been randomized. The trial will be activated at additional international sites in late 2017 and 2018. We are seeking to recruit sites who wish to collaborate. Clinical trial information: NCT01554397.