A Phase II Clinical Study Using OCZ103-OS in Patients With Unresectable and Locally Recurrent or Metastatic Colorectal Cancer Undergoing Standard Chemotherapy (mFOLFOX6 or FOLFIRI) as Second-Line Treatment
1. Histologically or cytologically proven diagnosis of adenocarcinoma of the
colon/rectum with evidence of (1) unresectable and, locally recurrent, or (2)
2. Failure of first-line therapy(5-Fu-based therapy +/- bevacizumab) for metastatic
3. At least one (1) unidimensionally measurable lesion (on spiral CT scan).
4. 18 years of age or older.
5. ECOG performance status 0, 1 or 2.
6. Serum aspartate transaminase (AST), serum alanine transaminase (ALT), serum alkaline
phosphatase (ALP) ≤ 2.5 x upper limit of normal (ULN), or AST,ALT, ALP ≤ 5 x ULN if
liver function abnormalities are due to underlying malignancy
7. Total serum bilirubin ≤ 1.5 x ULN
8. Lipase and amylase within normal limits or abnormal limits but deemed not clinically
9. Absolute neutrophil count (ANC) ≥ 1500/µL (1.5 x 10e9/L)
10. Platelets ≥ 100,000/µL (100 x 10e9/L)
11. Hemoglobin ≥ 90 g/L
12. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 ml/min. The
Cockcroft-Gault formula to be used is as follows:
eCcr=(140-age)x Mass(in kilogram)x Constant/Serum Creatinine(in µmol/L)
Where Constant is 1.23 for men and 1.04 for women.
13. Normal or abnormal ECG. If ECG shows abnormalities, they must be deemed not
14. Signed and dated Informed Consent Form indicating that the subject (or legally
acceptable representative) has been informed of all the pertinent aspects of the
trial prior to enrollment.
15. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests, and other trial procedures.
16. Life expectancy, in the opinion of the investigator, > 3 months.
1. Systolic Blood Pressure <100 mmHg (if deemed clinically significant by the treating
2. Uncontrolled diabetes, severe renal impairment or pancreatitis.
3. Concomitant therapy with other investigational agents or participation in another
clinical trial within 30 days prior to enrollment.
4. Any of the following conditions: Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2;
atrial fibrillation of any grade; QTc interval > 450 msec for males or > 470 msec for
females or uncontrolled intercurrent illness, e.g. unstable angina; severe coronary
disease, ventricular arrhythmias, bradycardia < 50 bpm; a history of additional risk
factors for torsades de pointes (e.g., heart failure, hypokalemia or family history
of Long QT Syndrome).
5. Active uncontrolled bacterial infection.
6. Concurrent use of drugs that could prolong QT interval (NB: pentamidine is known to
induce torsades de pointes) (see Appendix II: List of drugs that could prolong QT
interval / we also suggest that you refer to the following link:
7. Concurrent use of nephrotoxic drugs (depending on the medical health status of the
patient and based on the judgment of the investigator), including but not limited to
aminoglycosides, ampho B, foscarnet and cidofovir.
8. Concurrent use of drugs such as Rifampine and Lamivudine, since these that may be
associated with pancreatitis.
9. Prior malignancy other than colorectal cancer (except for adequately treated
carcinoma in situ of the cervix, non-melanoma skin cancer or localized prostate
cancer with undetectable PSA level) unless the prior malignancy was diagnosed and
definitively treated at least five (5) years previously with no subsequent evidence
10. Clinically significant non-malignant lung disease.
11. History of allergy or hypersensitivity to pentamidine.
12. Pregnancy or breastfeeding. All female patients with reproductive potential must have
a negative pregnancy test (serum or urine) prior to first dose of study medication.
13. Severe acute or chronic medical or psychiatric condition, or laboratory abnormality
that would impart, in the judgement of the investigator, excess risk associated with
trial participation of study drug administration, or which in the judgement of the
investigator, would make the subject inappropriate for entry into this trial.
14. Use of oral anticoagulants (LMWH is acceptable)