Radiochemotherapy +/- Durvalumab for Locally-advanced Anal Carcinoma. A Multicenter, Randomized, Phase II Trial of the German Anal Cancer Study Group
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- Same as current
Summary
- Conditions
- Anal Cancer
- Anal Cancer Stage II
- Anal Cancer Stage III
- Anal Carcinoma
- Type
- Interventional
- Phase
- Phase 2
- Design
- Allocation: RandomizedIntervention Model: Parallel AssignmentMasking: None (Open Label)Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 125 years
- Gender
- Both males and females
Description
Anal squamous cell carcinomas (ASCC) are increasing in frequency across the developed world. There is a strong rationale for combining the PD-L1 immune checkpoint inhibitor durvalumab with radiochemotherapy (RCT) in patients with ASCC. First, although primary RCT with concurrent mitomycin C and 5-fl...
Anal squamous cell carcinomas (ASCC) are increasing in frequency across the developed world. There is a strong rationale for combining the PD-L1 immune checkpoint inhibitor durvalumab with radiochemotherapy (RCT) in patients with ASCC. First, although primary RCT with concurrent mitomycin C and 5-fluorouracil (MMC/5-FU) is the standard treatment for ASCC, the 3-year DFS in patients with locally-advanced disease is only in the range of 60%. Second, approximately 80-90% of patients with ASCC are human papilloma virus (HPV)-positive, which is associated with higher tumor "immunogenicity" in this malignancy that is known to correlate with better response to RCT as well as PD-1/PD-L1 immune checkpoint inhibitors. Also, PD-L1 expression was observed in 33%-62% of patients with locally advanced non-metastatic ASCC that correlated with tumor stage. Third, inhibition of the PD-1/PD-L1 axis showed encouraging responses in recurrent/metastatic ASCC in two phase Ib/II trials. Fourth, several data indicate complementary roles between R(C)T and immunotherapy. Fifth, R(C)T can induce PD-L1 upregulation with resulting dysfunction in CD8+ T-cells, and addition of anti-PD-L1 to R(C)T can overcome T-cell suppression to reinvigorate immune surveillance. First clinical studies have demonstrated promising findings for the combination of RCT and immunotherapies. Thus, based on the above data, RCT combined with durvalumab is expected to be more effective than primary RCT alone. Altogether, the hereby proposed RADIANCE multicenter, randomized phase II trial aims to improve the current standard treatment by incorporating durvalumab to the primary MMC/5-FU-based RCT in patients with locally-advanced ASCC (T2=>4cm Nany, stage IIB-IIIC).
Tracking Information
- NCT #
- NCT04230759
- Collaborators
- Not Provided
- Investigators
- Not Provided