DNA Repair Inhibitor & Irradiation on Melanoma

Summary

Phase I trial will be conducted in patients suffering local metastatic melanoma with relapsed cutaneous/subcutaneous tumors including melanoma-in-transit. Based on the preclinical data package, DNA Therapeutics has considered that the risk-benefit ratio of DT01 supports the initiation of a phase I clinical study in this population. The recommended starting dose of DT01 for the first injection to human was based on NOAELs and Maximum Recommended Starting Dose (MRSD) calculations and by considering both local and systemic approaches. It was set at 16 mg (4 mg per injection site, 2 injections per tumor, 2 tumors to be treated). This starting dose will be increased up to 96 mg if no DLT occurred during dose escalation.

DT01 will be locally administered by peritumoral subcutaneous and/or intratumoral injections in combination with hypo-fractionated radiotherapy (RT) (10x 3 Gy) and chloroquine (100 mg oral QD) starting one week before DT01 and RT treatments. DT01 will be administered 3 times a week during two weeks; The study will be an open, non-randomised, multicentre, phase I dose escalation (16, 32, 48, 64 and 96 mg) safety study with a 3+3 design.

The purpose of this study will be to evaluate the safety, tolerance, pharmacokinetics of DT01 in association with palliative radiotherapy and to evaluate pharmacodynamics and the anti-tumor activity of DT01 according to RECIST criteria on day 26, 40 and 54. The duration of response (Time-To-Local Recurrence, TTLR), will be monitored 3, 6, 9 and 12 months after the beginning of the DT01 treatment.

Conditions

• Local Metastatic Melanoma

Interventions

DRUG

DT01

DT01 starting dose will be 16 mg and it is planned to be increased to 32, 48 mg and 64 mg, or higher. DT01 will be administered 3 times a week (e.g., Mondays, Wednesdays and Fridays) over 2 weeks (6 administrations of DT01 in total) at least 3 hours prior to the radiotherapy sessions.

Sponsors & Collaborators

• DNA Therapeutics

  lead INDUSTRY

Principal Investigators

• Christophe LE TOURNEAU, MD · Institut Curie - National Coordinator

• Marie-Françoise AVRIL, MD · Groupe Hospitalier Cochin - Hôtel Dieu-Broca

• Philippe SAIAG, MD · Hospital Ambroise Paré Paris

• Céleste LEBBE, MD · Hôpital Saint-Louis

• Jean-Jacques GROB, MD · Hôpital de la Timone

• Brigitte DRENO, MD · Hôpital hôtel-Dieu

• Caroline DUTRIAUX, MD · Hôpital Saint-André

• Laurent MORTIER, MD · Hôpital Claude-Huriez

• Eve MAUBEC, MD · APHP Hôpital Bichat - Claude Bernard

• Luc THOMAS, MD · Centre Hospitalier Lyon Sud

• Jean-Philippe LACOUR, MD · CHU de Nice - Archet 2

• Pascal JOLY, MD · Hôpital Charles Nicolle

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-10-31

Primary Completion

2015-07-31

Completion

2015-07-31

Countries

• France

Study Locations