Abstract 3895
Background
The standard treatment for cT3-4 N0-1 rectal cancer is preoperative chemo-radiation therapy (CT/RT). The combination of capecitabine plus long course radiotherapy (RT) is standard therapy in locally advanced rectal cancer. Pathologic Complete remission (pCR) can be considered as surrogate end point of efficacy of treatment in terms of disease free survival (DFS). Clinical complete remission (cCR) is an important endpoint for “wait and see” strategy. In the PACIFIC trial in non-small cell lung cancer the patients were treated with durvalumab maintenance after CT/RT with advantage in progression free survival. “Abscopal effect” is proposed as mediator of systemic effects after localized RT. Preclinical data points heavily toward a strong synergy between RT and immune treatments. Recent reports already illustrate that such a systemic effect of RT is possible when enhanced by targeted immune treatments.
Trial design
This is a prospective phase II, open label, single arm, multi-centre study to evaluate, in patients with operable rectal cancer, activity of an innovative sequence: standard concomitant CT/RT therapy with 825 mg/m2 twice daily capecitabine every day and 5040 cGy radiotherapy for 5 days per week for 5 weeks followed by 1500 mg Q4W durvalumab for 3 administration. After 9-10 weeks from neoadjuvant therapy will be performed re-staging with CT and MRI scan. Surgery will be performed at week 10-12 from the end of CT/RT. Primary Objective: pCR rate, defined as a TRG 3-4 according to DWORAK criteria. Secondary Objectives: Safety of treatment with durvalumab; cCR rate after durvalumab treatment before surgery and DFS. cCR will be evaluated with clinical, endoscopic and radiological assessment to look for evidence of residual disease. DFS will be evaluated during a follow up of 5 years. Exploratory Objective: Biological translational analysis of tumor biomarkers will be performed on the endoscopy biopsy done at the diagnosis and on the biopsy performed after the CT/RT prior to treatment with durvavalumab. We have planned to enlist 60 patients in 7 centers with an enrollment period of 12 months, already underway.
Clinical trial identification
2018-004758-39.
Editorial acknowledgement
Legal entity responsible for the study
Tamberi Stefano.
Funding
AstraZeneca.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1452 - RBP-Jκ in colon cancer cells facilitates tumor associated macrophages (TAMs)-induced cell metastasis by secreting CXCL11
Presenter: Meng jie Liu
Session: Poster Display session 2
Resources:
Abstract
2786 - Development of a living organoid biobank derived from colorectal cancer patients: towards personalized medicine
Presenter: Federica Papaccio
Session: Poster Display session 2
Resources:
Abstract
3351 - Microsatellite Instability Detection in Colorectal Cancer: 44-Center Comparison between the Idylla MSI Assay and Routine Molecular and Immunohistochemistry Tests on Formalin-Fixed Paraffin-Embedded Tissue
Presenter: Xavier Matias-guiu
Session: Poster Display session 2
Resources:
Abstract
4901 - Expression profile of EPHB3 and its prognostic significance in colorectal cancer progression (Running head: Prognostic value of EPHB3 in colorectal cancers)
Presenter: Bogun Jang
Session: Poster Display session 2
Resources:
Abstract
5030 - A pan-ErbB family inhibitor, AF8c, promotes apoptosis by DR5/Nrf2 activation via ROS in colorectal cancer cells
Presenter: Soyeon Jeong
Session: Poster Display session 2
Resources:
Abstract
5053 - Frequent BRAF, GNAS and SMAD4 mutations identified in Colorectal Mucinous Carcinomas
Presenter: Sun Mi Lee
Session: Poster Display session 2
Resources:
Abstract
5220 - Impact of CCL4 knockout using CRISPR Cas-9 technology on colorectal tumor progression
Presenter: Roba Barakat
Session: Poster Display session 2
Resources:
Abstract
5330 - Independent clinical validation of a gene expression profile to predict benefit of 5-FU in metastatic colorectal cancer
Presenter: Ida Buhl
Session: Poster Display session 2
Resources:
Abstract
5515 - WRN mutated Colorectal Cancer (CRC) is characterized by a distinct molecular and immunological profile
Presenter: Andreas Seeber
Session: Poster Display session 2
Resources:
Abstract
5716 - Mutation analysis of B2M gene in colorectal cancer patients with microsatellite instability
Presenter: Ivana Kašubová
Session: Poster Display session 2
Resources:
Abstract