Dataset Information

First-in-human phase I study of the DNA-repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma.

ABSTRACT:

Background

DT01 is a DNA-repair inhibitor preventing recruitment of DNA-repair enzymes at damage sites. Safety, pharmacokinetics and preliminary efficacy through intratumoural and peritumoural injections of DT01 were evaluated in combination with radiotherapy in a first-in-human phase I trial in patients with unresectable skin metastases from melanoma.

Methods

Twenty-three patients were included and received radiotherapy (30 Gy in 10 sessions) on all selected tumour lesions, comprising of two lesions injected with DT01 three times a week during the 2 weeks of radiotherapy. DT01 dose levels of 16, 32, 48, 64 and 96 mg were used, in a 3+3 dose escalation design, with an expansion cohort at 96 mg.

Results

The median follow-up was 180 days. All patients were evaluable for safety and pharmacokinetics. No dose-limiting toxicity was observed and the maximum-tolerated dose was not reached. Most frequent adverse events were reversible grades 1 and 2 injection site reactions. Pharmacokinetic analyses demonstrated a systemic passage of DT01. Twenty-one patients were evaluable for efficacy on 76 lesions. Objective response was observed in 45 lesions (59%), including 23 complete responses (30%).

Conclusions

Intratumoural and peritumoural DT01 in combination with radiotherapy is safe and pharmacokinetic analyses suggest a systemic passage of DT01.

SUBMITTER: Le Tourneau C

PROVIDER: S-EPMC4891504 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Publications

First-in-human phase I study of the DNA-repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma.

Le Tourneau C C Dreno B B Kirova Y Y Grob J J JJ Jouary T T Dutriaux C C Thomas L L Lebbé C C Mortier L L Saiag P P Avril M F MF Maubec E E Joly P P Bey P P Cosset J M JM Sun J S JS Asselain B B Devun F F Marty M E ME Dutreix M M

British journal of cancer 20160503 11

<h4>Background</h4>DT01 is a DNA-repair inhibitor preventing recruitment of DNA-repair enzymes at damage sites. Safety, pharmacokinetics and preliminary efficacy through intratumoural and peritumoural injections of DT01 were evaluated in combination with radiotherapy in a first-in-human phase I trial in patients with unresectable skin metastases from melanoma.<h4>Methods</h4>Twenty-three patients were included and received radiotherapy (30 Gy in 10 sessions) on all selected tumour lesions, compr ...[more]

PMID: 27140316

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Dataset Information

First-in-human phase I study of the DNA-repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma.

Background

Methods

Results

Conclusions

Publications

First-in-human phase I study of the DNA-repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma.

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