DNA Repair Inhibitor & Irradiation on Melanoma

Inclusion Criteria:

* Patients with histologically confirmed metastatic melanoma with relapsed cutaneous tumors, including melanoma-in-transit, who are not eligible for immediate surgery or refractory to conventional treatment;
* Patients with at least two measurable tumors of ≤ 4cm in largest diameter. Treated tumors must not be previously irradiated.

The consideration of tumor size and number for the 5th and expansion cohorts can be revised based on the observation for the 4 first cohorts, in particular the initial indication of efficacy, after an agreement between Principal Investigators, the DSMB and the Sponsor.

* Normal haematopoietic function as assessed by a complete blood count including differential count.

  i.Absolute neutrophil count ≥ 1.5 x 109/L; ii.Platelet count ≥ 100 x 109/L; iii.Haemoglobin ≥ 10 g/dL (transfusions are permitted);
* No clinically relevant abnormalities in the results of the pre-study laboratory tests:

  i.Creatinine ≤ 1.5 times UNL (upper normal of the limit) ; ii.Bilirubin ≤ 1.5 times UNL; iii.ASAT (SGOT) ≤ 2.5 times the upper limit of normal if no liver metastasis and ≤ 5 times the upper limit of normal in the presence of liver metastasis ; iv.ALAT (SGPT) ≤ 2.5 times the upper limit of normal if no liver metastasis and ≤ 5 times the upper limit of normal in the presence of liver metastasis;
* Age ≥18 years old;
* The patient is willing and able to comply with the protocol for the duration of the study, including 1 day of hospitalization for PK sample at Day 1 and scheduled follow-up visits and examinations to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.

Exclusion Criteria:

* Presence of any serious concomitant systemic disorders incompatible with the study (e.g. active infection);
* Known or suspected Central Nervous System (CNS) metastases including leptomeningeal metastases (unless the patient has been previously treated and the patient meets the three following criteria: is asymptomatic, has no evidence of active CNS metastases for more than 3 months prior to enrollment, and has no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days);
* Patients with a history of porphyria;
* Patients with active psoriasis;
* Clinically significant hepatic disease (particularly cirrhosis) or renal disease;
* Severe gastrointestinal, neurological and blood disorders;
* Patients receiving anti-vitamin K therapy within 10 days prior to first dose of study treatment (Low Molecular Weight Heparin (LMWH) therapy is allowed);
* Anticancer therapy (chemotherapy, hormone therapy or immunotherapy) within 4 weeks prior to first dose of study treatment and immunotherapy with Ipilimumab, within 3 months prior to first dose of study treatment ;
* Patients receiving cyclosporin within 10 days prior to first dose of study treatment;
* Patients intended to receive any systemic anticancer therapy within 26 days (±2 days) from the anticipated date of the first administration of DT01
* Pregnant or breast-feeding women, or women of child-bearing potential unless effective methods of contraception are used. Child-bearing potential is defined as:

  i.Has experienced menarche, and ii.Has not undergone successful surgical sterilisation, and iii.Is not post-menopausal (amenorrhea \> 12 consecutive months or is on Hormone Replacement Therapy (HRT) with a documented plasma or serum FSH \> 35 IU/L. iv.Women using oral, implanted, injectable, mechanical or barrier products for the prevention of pregnancy, or who are practising abstinence, or where the partner is sterile (for example, a vasectomy) should be considered to be of child-bearing potential
* Concomitant participation to another study;
* Hypersensitivity to 4-aminoquinoline compounds (chloroquine) or to any of its derivatives;
* HIV and Hepatitis B or C positive patients;
* Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2
* Retinal or visual field changes attributable to previous chloroquine administration or any other etiology;
* Any reason why, in the Investigator's opinion, the patient should not participate in the study.
* Disease burden judged high, and therefore the patient can not likely benefit from the proposed treatment.
* Significant coagulation abnormalities