3578 - OBLITERATE: A Phase II Pragmatic Trial Testing Local Ablative Therapy in Oligoprogressive Thoracic Malignancies
Presenter(s)
I. F. Nwoguh1, X. Zhao1, E. Kim2, M. Parikh3, T. Le4, T. Dodd4, L. Morris4, L. Qi5, S. Feinstein6, C. Park7, A. Shah8, and M. E. Daly9; 1Department of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA, 2Department of Hematology and Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA, 3UC Davis Comprehensive Cancer Center, Sacramento, CA, 4University of California Davis Comprehensive Cancer Center, Sacramento, CA, 5Public Health Science, University of California Davis, Davis, CA, 6Department of Radiation Oncology, University of California, Irvine, Orange, CA, 7Department of Hematology and Oncology, University of California Irvine School of Medicine, Irvine, CA, 8Department of Radiology, University of California Davis Comprehensive Cancer Center, Sacramento, CA, 9Department of Radiation Oncology, University of California - Irvine, Orange, CA
Purpose/Objective(s):
Oligoprogressive (OP) cancer is characterized by progression at a limited number of sites with otherwise systemically well-controlled disease, reflecting the emergence of treatment- resistant clones potentially amenable to local eradication. The randomized phase 2 CURB trial demonstrated a significant progression-free survival (PFS) benefit with LAT in oligoprogressive non-small cell lung cancer (NSCLC), and randomized phase 3 trials testing LAT in NSCLC are ongoing. Prospective studies indicate LAT is generally well tolerated, ; however, controversy remains around appropriate patient selection for LAT and clinically meaningful endpoints for randomized trials testing LAT for oligoprogression. We activated the single institution pragmatic phase 2 OBLITERATE trial (NCT06103682) to rapidly evaluate the impact of LAT on disease control using time to next systemic therapy as a meaningful and measurable endpoint in patients with oligoprogressive thoracic malignancies.
Materials/Methods:
Adults (=18 years) with histologically confirmed NSCLC or small cell lung cancer (SCLC) receiving any systemic therapy who develop oligoprogressive disease (=5 progressing or new lesions) after at least 3 months of clinical benefit are eligible. All progressing lesions must be amenable to LAT, and patients continue the same systemic therapy. LAT consists of stereotactic ablative radiotherapy (SABR) or interventional radiology–guided ablation, delivered per institutional standards at the discretion of the treating physician. The primary endpoint is the rate of continuation of the same systemic therapy at 3 months post-LAT. Patients are followed with standard of care imaging at treating MD discretion. The null hypothesis is that the true continuation of therapy rate is 0.1 and the alternative hypothesis is that the true rate is 0.3. The sample size calculation for the first 25 participants (10 lead in and 15 additional) enrolled in each cohort is based on a Simon’s minimax two-stage design, assuming a one-sided significance level of 0.05 and 80% power. Two interim analyses are planned for futility for each cohort. Once the 25 th participant is enrolled, efficacy will be examined and if 6 or more participants with controlled disease among these 25 patients, then an additional 25 participants will be enrolled in Expansion 2 resulting in a cumulative total of 50 participants in each cohort.
Results:
With a total of 50 patients per cohort, we will have 98% power to reject the null hypothesis at a one-sided significance level of 0.05. Participants are followed for up to five years to assess durability of disease control and long-term outcomes. This pragmatic trial design with broad eligibility allows for rapid identification of patient subgroups most promising for further study. Accrual commenced December 2023 and is ongoing.
Conclusion:
Ongoing analysis for late break abstract.