Trial to Determine Optimal Phase II Dose of the Oral Dual CAIX Inhibitor/ Radiosensitizer

Inclusion Criteria:

* Patients with histologically or cytologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective.
* Age 18 year or older
* Performance status, WHO = 0 - 2
* Subject must have adequate bone marrow, renal and hepatic function per local laboratory reference rage as follows:

Bone marrow: absolute neutrophil count (ANC) \>/= 1,500/ul; platelets \>/= 100,000/mm3 (independent of platelet transfusion, within 3 months prior to starting study drug); haemoglobin \>/= 9.0 g/dL

Renal function: serum creatinine \</= 2.0 mg/dL or calculated creatinine clearance \>/= 50 mL/min

Hepatic function and enzymes: AST and ALT \</= 2.5 x the upper limit of normal (ULN) of institution's normal range. Bilirubin \</=1.5 x INL.

Subjects with liver metastases may have an AST and ALT of \</= 5.0 x ULN

* Measurable disease (RECIST, version 1.1)
* Subjects with known brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and or radiation therapy followed by 21 days of stable neurologic function and no evidence of CNS disease progression as determined by comparing a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan performed during screening to a prior scan performed at least 4 weeks earlier and provided that the subject is asymptomatic, has no evidence of cavitation or haemorrhage and is on a stable dose of dexamethasone.
* Females must have negative results for pregnancy tests performed:

At screening on a serum sample obtained within 7 days prior to initial study drug administration, and Prior to dosing on a urine pregnancy test will be obtained prior to study drug administration (cycle 1, day 1).

* No breast feeding.
* If female, subject must be either postmenopausal for at least 2 years, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or practicing at least one of the following methods of birth control:

Total abstinence from sexual intercourse as the preferred life style of the subject, periodic abstinence is not acceptable; Vasectomized partner; Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration (if the subject is currently using a hormonal contraceptive, she should also use a barrier method during the study and for 1 months after study completion); Intrauterine device (IUD); Double barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or creams);

\- If male, subject must be surgically sterile or practicing at least 1 of the following methods of contraception and refrain from sperm donation, from initial drug administration until 90 days after the last dose of study drug: Partner(s) using an IUD; Partner(s) using hormonal contraceptives (oral, vaginal, parenteral or transdermal); Subject and/or partner(s) using double-barrier method (condoms, contraceptive sponge, diaphragm, or vaginal ring with spermicidal jellies or creams).

Total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not acceptable.

* Ability to swallow and take oral medication. Patients that are dependent on a feeding tube can only be included in the study when entered in the last cohort, in which the PK of crushed study medication is the object of study.
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
* Willing and able to undergo blood sampling for pharmacokinetics
* Must voluntarily sign and date each informed consent, approved by an independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

* If the subject has clinically significant and uncontrolled major medical condition(s) including but not limited to:

Uncontrolled seizure disorder, including focal or generalised seizure within the last 12 months; Uncontrolled nausea/vomiting/diarrhea; Active uncontrolled infection, including HIV and hepatitis (HBV, HCV) Symptomatic congestive heart failure, irreversible cardiac arrhythmias, acute or subacute coronary syndromes within the last year.

Psychiatric illness/social situation that would limit compliance with study requirements Any medical condition, with the opinion of the study investigator, places the subject at an unacceptably high risk for toxicities.

* Female subject is pregnant or breastfeeding.
* Subject has received any of the following anti-cancer therapies 21 days prior to the first dose of study drug:

Chemotherapy, immunotherapy, radiotherapy.

Any investigational therapy, including targeted small molecule agents. With the following exceptions:

* Hormonal anticancer therapy must be stopped 7 days before starting day 1 of cycle 1 (C1D1)
* Hormones for hypothyroidism, estrogen replacement therapy (ERT) or agonists required or suppress serum testosterone or estrogen levels (e.g. LHRH, GnRH, etc) for subjects with prostate, breast and ovarian cancer if on a stable dose for 21 days prior to the first dose of study drug.
* Subject has received a biological agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.
* Subject who requires parenteral nutrition, tube feeding or has evidence of partial bowel obstruction or perforation within 28 days prior to study drug administration.
* The subject has had another active malignancy within the past 3 years except for any cancer in situ that the Principal Investigator considers to be cured.
* In the opinion of the investigator, the subject is an unsuitable candidate to receive DTP348.