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Radiochemotherapy +/- Durvalumab for Locally-advanced Anal Carcinoma. A Multicenter, Randomized, Phase II Trial of the German Anal Cancer Study Group

2020-01-23 12:48:52 | BioPortfolio

Summary

The RADIANCE multicenter, randomized phase II trial will assess the efficacy of durvalumab, a PD-L1 immune checkpoint inhibitor, in combination with primary mitomycin C (MMC)/5-fluorouracil (5-FU)-based radiochemotherapy (RCT) in patients with locally-advanced anal squamous cell carcinoma (ASCC).

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-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).

Study Design

Conditions

Anal Cancer

Intervention

Chemotherapy, Radiation, Durvalumab

Location

Radioonkologie und Strahlentherapie
Berlin
Germany
12203

Status

Recruiting

Source

Goethe University

Results (where available)

View Results

Links

Published on BioPortfolio: 2020-01-23T12:48:52-0500

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Medical and Biotech [MESH] Definitions

Drug therapy given to augment or stimulate some other form of treatment such as surgery or radiation therapy. Adjuvant chemotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.

Proposed as an adjuvant to cancer chemotherapy; may have radiation protective properties.

Tumors or cancer of the anal gland.

Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment.

A dopamine antagonist that is particularly useful in treating the nausea and vomiting associated with anesthesia, mildly emetic cancer chemotherapy agents, radiation therapy, and toxins. This piperazine phenothiazine does not prevent vertigo or motion sickness. (From AMA Drug Evaluations Annual, 1994, p457)

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