Phase I Study of CBP501 and Cisplatin in Patients With Advanced Refractory Solid Tumors

Inclusion Criteria:

* Signed informed consent obtained prior to initiation of any study-specific procedures.
* Pathologically-confirmed, locally advanced or metastatic solid tumors, refractory to standard therapy.
* Male or female patients aged 18 years or over.
* ECOG Performance Status (PS): 0-1.
* Life expectancy \> 3 months.
* Previous anticancer treatment must be discontinued at least 3 weeks prior to first dose of study treatment (6 weeks for mitomycin C; 6 weeks for anti-androgen therapy if discontinued prior to treatment initiation, with the exception of 8 weeks for bicalutamide).
* Adequate organ function including the following:
* Bone Marrow: absolute neutrophil count (ANC) ³ 1.5 x 109/L, platelet count ³ 100 x 109/L, hemoglobin ³ 9 g/dL
* Hepatic: Bilirubin £ 1.5 x the upper limit of normal (ULN), aspartate transaminases (AST/SGOT) and alanine transaminases (ALT/SGPT) £ 2.5 x ULN (or ≤ 5 x ULN if liver metastases are present), INR £ 1.5 x ULN
* Renal: Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ³ 70 mL/min (calculated according to the Cockroft and Gault formula)
* Metabolic: serum potassium, calcium and magnesium ³ lower limit of normal (LLN)
* Creatine phosphokinase isoenzymes: CPK-MB, CPK-MM ≤ ULN
* Troponin I serum level within normal values
* Female patients of child-bearing potential must have a negative pregnancy test and use at least one form of contraception as approved by the investigator for 4 weeks prior to the study and 4 months after the last dose of study drug. For the purposes of this study, child-bearing potential is defined as: "All female patients unless they are post-menopausal for at least one year or are surgically sterile".
* Male patients must use a form of barrier contraception approved by the investigator during the study and for 4 months after the last dose of study drug.
* Ability to co-operate with the treatment and follow-up.

Exclusion Criteria:

* Radiation therapy to more than 30% of the bone marrow prior to entry into the study.
* Prior chemotherapy with nitrosoureas or high dose carboplatin (AUC \> 6 mg/mL), prior mitomycin C cumulative dose ³ 25 mg/m², prior bone marrow transplant or intensive chemotherapy with stem cell support.
* Presence of any serious concomitant systemic disorders incompatible with the study (e.g. uncontrolled congestive heart failure, active infection, etc.).
* Any previous history of another malignancy (other than cured basal cell carcinoma of the skin or cured in-situ carcinoma of the cervix) within 5 years of study entry.
* Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance.
* Evidence of peripheral neuropathy \> grade 1 according to NCI-CTCAE Version 3.
* Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to study entry.
* Pregnant or breast-feeding patients or any patient with childbearing potential not using adequate contraception.
* Known HIV, HBV, HCV infection.
* Active CNS metastasis: patients with a history of CNS metastases will be eligible if they have been treated and are stable without symptoms for 4 weeks after completion of treatment, with image documentation required, and must be either off steroids or on a stable dose of steroids for \> 1 week prior to enrollment.