A Safety Study of Pentamidine in Patients With Metastatic Colon Cancer Undergoing Standard Chemotherapy as Second-line and/or Third-line Treatment

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate the safety and possible efficacy of the use of pentamidine in the treatment of colon cancer metastasis in subjects receiving standard therapy.

Official Title
-----------------
A Phase I/II Clinical Study Using Pentamidine in Patients With Metastatic Colon Cancer Undergoing Standard Folinic Acid, 5-Fluorouracil, or Capecitabine and Oxaliplatin Chemotherapy as Second-line and/or Third-line Treatment

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: pentamidine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically proven diagnosis of adenocarcinoma of the colon or rectum with evidence of (1) unresectable, locally recurrent, or (2) metastatic disease Failure of first-line or second-line therapy for colorectal cancer At least one unidimensional measurable lesion (on spiral CT scan) 18 years of age or older ECOG performance status 0, 1 or 2 Serum aspartate transaminase (AST) serum alanine transaminase (ALT) £ 2.5 x upper limit of normal (ULN), or AST and ALT £ 5 x ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin £ 1.5 x ULN Serum albumin ≥ 3.0 g/dL lipase within normal limits Absolute neutrophil count (ANC) ≥ 1500/uL (1.5 x 109/L) Platelets ≥ 100,000/uL Hemoglobin ≥ 9.0 g/dL Serum creatinine £ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min Magnesium ≥ lower limit of normal CEA level ≥ 3.4 ng/ml Normal ECG Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures Life expectancy, in the opinion of the investigator, > 3 months Exclusion Criteria: BP < 100 (systolic) History of renal disease, pancreatitis, or diabetes mellitus Peripheral sensory neuropathy (> Grade 1, as per NCI CTCAE version 3.0) Concomitant therapy with other investigational agents or participation in another clinical trial 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 Active uncontrolled bacterial infection Concurrent use of drugs that could prolong QT interval Concurrent use of nephrotoxic drugs, including aminoglycosides, ampho B, foscarnet, cidofovir Concurrent use of drugs that may be associated with pancreatitis Concurrent active cancer originating from a primary site other than colon/rectum, except for surgically treated nonmelanoma skin cancer, in situ cervical cancer, or localized prostate cancer with undetectable PSA level Co-existing lung disease History of allergy or hypersensitivity to pentamidine 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. 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. On oral anticoagulants

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single arm<br>Use of pentamidine in second and/or third line metastatic colon cancer | Drug: pentamidine<br>* one dose of 4 mg/kg to two dose of 4 mg/kg with possibility of escalated to two dose of 6 mg/kg with or without standard chemotherapy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Any severe events, tumor marker CEA, and tumor size (CT scan) |  | Three Months |