Clinical trial NCT01378143: Using OCZ103-OS in Patients With Unresectable and Locally Recurrent or Metastatic Colorectal Cancer Undergoing Standard Chemotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Colorectal Cancer
Pentamidine bis(2-hydroxyethanesulfonate)
OCZ103-OS
Standard of Care
Lead sponsor: Oncozyme Pharma Inc.
Sponsor class: INDUSTRY
First posted: 2011-06-22
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the safety and efficacy of the use of OCZ103-OS in combination with standard of care as a second line treatment in subjects with unresectable and locally recurrent or metastatic colorectal cancer.

Detailed description: This is a single arm, open label study to investigate the safety and efficacy of the use of OCZ103-OS in combination with standard therapy (mFOLFOX6 or FOLFIRI) as a second line treatment in subjects with unresectable and locally recurrent or metastatic colorectal cancer.

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically proven diagnosis of adenocarcinoma of the colon/rectum with evidence of (1) unresectable and, locally recurrent, or (2) metastatic disease.
2. Failure of first-line therapy(5-Fu-based therapy +/- bevacizumab) for metastatic colorectal cancer.
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 significant.
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 clinically significant.
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.

Exclusion criteria

1. Systolic Blood Pressure \<100 mmHg (if deemed clinically significant by the treating physician).
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: http://www.azcert.org/medical-pros/drug-lists/bycategory.cfm).
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 of recurrence.
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)

Primary outcomes:
measure: Tumor size (CT scan)
timeFrame: 2 years
measure: Progression free survival (PFS)
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
Secondary outcomes:
measure: Peak plasma concentration (Cmax) of OCZ103-OS
timeFrame: 2 months
measure: Number of participants with Adverse Events (AE) as a Measure of Safety and Tolerability
timeFrame: 2 years
measure: Objective response (OR)
timeFrame: 2 years
measure: Duration of response (DR)
timeFrame: 2 years
Other outcomes:
Locations:
city: Greenfield Park
country: Canada
facility: CSSS Champlain - Charles-Lemoyne Hospital
state: Quebec
city: Levis
country: Canada
facility: CSSS Alphonse-Desjardins (CHAU Hotel-Dieu de Levis)
state: Quebec
city: Montreal
country: Canada
facility: CHUM-St. Luc Hospital
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS-Centre de recherche Etienne-Le Bel
state: Quebec
city: St-Jérome
country: Canada
facility: CSSS St-Jérome
state: Quebec
city: Quebec
country: Canada
facility: Hotel-Dieu de Quebec
Study officials:
affiliation: Jewish General Hospital
name: Petr Kavan, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: CSSS Champlain - Charles-Lemoyne Hospital
name: Benoit Samson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Luc Hospital
name: Richard Letourneau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hotel-Dieu de Quebec
name: Felix Couture, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CSSS Alphonse-Desjardins
name: Felix Couture, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHUS-Centre de recherche Etienne-Le Bel
name: Annie Beaudoin, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: CSSS St-Jérome
name: Jacques Jolivet, MD
role: PRINCIPAL_INVESTIGATOR
References: