Abstract 462TiP
Background
Anaplastic thyroid cancer (ATC) is a rare but deadly malignancy with a historical median overall survival (OS) of 6months. Progress has been made in patients (pts) with BRAF mutated (BRAFm) ATC with dabrafenib/trametinib (DT), leading to an OS of 14.5 months. These drugs are approved in the United States and few other countries. However, options are limited for those without a BRAF mutation (BRAFwt). Presently, there are several clinical trials for ATC enrolling at MD Anderson (MDA). Participation in these trials lack diversity due to the inability of many pts to access MDA.
Trial design
GRASSROOT is a prospective, Master Observational Trial (MOT) for ATC pts who are ineligible or unable to participate in clinical trials. Patients will be offered treatment regimens with commercially available drugs in the US, Latin America, Europe, Asia, and the Middle East. The objective of this study is to gather real world comprehensive data on the median OS of ATC pts treated outside of the traditional clinical trial, with treatment regimens like what is offered on the clinical trial. Enrolling sites will consent pts and then assign treatments based on the stage and BRAF status, carrying out the treatments per MDA treatment algorithms. Treatment regimens will be modified based on availability. Pts with BRAFm ATC tumors will be treated with neoadjuvant DT and pembrolizumab (P) prior to surgery followed by either chemoradiation (for stage IVB disease) followed by DTP or continue DTP post operatively for stage IVC disease. Pts with BRAFwt ATC tumors will be offered surgery followed by chemoradiation followed by adjuvant P or lenvatinib and P for stage IVC disease. High level outcome data will be recorded in a RedCap database. The OS between patient groups will be compared with the log-rank test. Tumor mutation data and patient reported outcomes, assessed by using the MDASI-HN scale, will also be collected. To provide 90% power for a 0.67 hazard ratio, the study will enroll 459 patients over next 8 years at 14 national and international sites with an intended follow up of at least 2 years. The clinical trial was IRB at MDA approved in July 2024 and is in the process of opening other sites.
Clinical trial identification
Awaiting registration with clinical trials.gov. However, per website, given this is an observation study, it is not madatory to register.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
MD Anderson- Petrick Funds.
Disclosure
R. Dadu: Financial Interests, Personal, Research Funding: Exelixis, Eisai, Merck, AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: Exelixis, Bayer, Novartis. M. Zafereo: Financial Interests, Personal, Research Grant: Merck', Eli Lilly. A. Maniakas: Financial Interests, Personal, Research Funding: Jazz Rharmaceuticals, Thryv Therapeutics. N. Busaidy: Financial Interests, Personal, Speaker, Consultant, Advisor: Exelixis, Eisai. R. Ferrarotto: Financial Interests, Personal, Advisory Role: Regeneron, Prelude therapeutics, Elevar therapeutics, Coherus bioscience, Eisai, Remix Therapeutics, Sanofi/Aventis, LabCorp Drug Development, Rgenta, RAPT Therapuetics; Financial Interests, Institutional, Research Funding: Merck, Pfizer/ EMD soreno, Ayala Pharmaceuticals, Prelude therapeutics, ISA pharmaceuticals, Viracta therapeutics, Gilead Sciences, Seagen, Remix. M.E. Cabanillas: Financial Interests, Personal, Advisory Board, clinical trial planning: Thryv; Financial Interests, Personal, Advisory Board, advising on patient education materials: Novartis; Financial Interests, Personal, Advisory Board: Exelixis, Bayer; Financial Interests, Personal, Invited Speaker: Endocrine Society; Financial Interests, Institutional, Local PI, Grant funding for clinical trial: Genentech; Financial Interests, Institutional, Local PI, Grant funding for clinical trials: Merck; Non-Financial Interests, Personal, Member of Board of Directors: American Thyroid Associaion. All other authors have declared no conflicts of interest.