Phase I Clinical and Pharmacokinetic Study of CBP501 and Cisplatin Every 3 Weeks in Patients With Advanced Refractory Solid Tumors
- Signed informed consent obtained prior to initiation of any study-specific
- Pathologically-confirmed, locally advanced or metastatic solid tumors, refractory to
- 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
- 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.
- 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.