Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma
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Short-course radiation followed by mFOLFOX-6 plus avelumab for locallyadvanced rectal adenocarcinoma Ali Shamseddine1*†, Youssef H. Zeidan2†, Malek Kreidieh1, Ibrahim Khalifeh3, Rim Turfa4, Joseph Kattan5, Deborah Mukherji1, Sally Temraz1, Kholoud Alqasem4, Rula Amarin4, Tala Al Awabdeh4, Samer Deeba6, Faek Jamali6, Issa Mohamad4, Mousa Elkhaldi4, Faiez Daoud7, Mahmoud Al Masri7, Ali Dabous7, Ahmad Hushki8, Omar Jaber9, Clement Khoury10, Ziad El Husseini1, Maya Charafeddine1, Monita Al Darazi1 and Fady Geara2
Abstract Background: Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. Methods: The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. (Continued on next page)
* Correspondence: [email protected] † Ali Shamseddine and Youssef H. Zeidan contributed equally to this work. 1 Department of Internal Medicine, Division of Hematology/Oncology, Naef K. Basile Cancer Institute- NKBCI, American University of Beirut Medical Center, Beirut, Lebanon Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, whi
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