Quinacrine-Capecitabine Combinatorial Therapy for Advanced Stage Colorectal ADenocarcinoma

Because of the well published safety profiles of both quinacrine and capecitabine, the Phase
I portion of our study will aim to determine the tolerability of both agents in combinations
when used at established clinical doses. This portion of the study will more closely resemble
a pilot study or feasibility study rather than a dose escalation Phase I trial. The objective
is to determine toxicities and adverse reactions, not a maximally tolerated dose. The
investigators hypothesize that there will be no toxic interactions at the pharmacokinetic or
pharmacodynamic level, and want to know the feasibility of using quinacrine and capecitabine
at their respective recommended single agent doses. Because capecitabine is already regarded
as standard treatment for colorectal cancer, the investigators will begin the study with a
full dose of capecitabine combined with a slightly lower dose of quinacrine. If the
safety-interim analysis does not detect an excess of toxicity, then subsequent patients will
be enrolled using the full dose of both drugs.

Inclusion Criteria:

- Patients much have histologically confirmed adenocarcinoma of the colon or rectum.

- Patients must have measurable recurrence or metastases in the liver and/or lungs.

- Patients must have prior chemotherapy for advanced colorectal cancer and have
previously received both an oxaliplatin and an irinotecan based regimen.

- Age > 18 years.

- Life expectancy greater than 4 weeks.

- ECOG performance status <3.

- Patients must have normal organ and marrow function.

- Patients must be able to swallow capsules.

- Patients must be able to understand and willing to sign a written informed consent
document.

- Patients are included regardless of KRAS/BRAF status.

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
the study or those who have not recovered from adverse events due to agents
administered more than 4 weeks earlier.

- Patients may not be receiving any other investigational agent.

- Patients with know brain metastases should be excluded from this clinical trial
because they often develop progressive neurological dysfunction that would confound
the evaluation of neurologic and other adverse events.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to quinacrine, capecitabine or fluorouracil.

- The concomitant use of quinacrine and primaquine is contraindicated.

- Uncontrolled intercurrent illness including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant women are excluded from this study.

- Patients with a baseline creatinine clearance of < 50 mL/min.

- Patients must be currently not treated with quinacrine or drugs related to quinacrine.

- Patients who require anti-arrhythmic treatment with amiodarone or any drug with a
quinidine-like effect on the heart or who have history of a malignant ventricular
arrhythmia unless they have a functioning automatic implantable cardio defibrillator
implanted.

- Patients who have a history of noninfectious hepatitis or alcoholism.

- Patients with a lifetime history of porphyria or psoriasis because it can exacerbate
these conditions.

- Patients with documented glucose-6-phosphate dehydrogenase deficiency.

- Patients with a lifetime history of seizure disorder.

- Patients with a lifetime history of dermatitis as an allergic/toxic reaction to any
medication.

- Patients with know dihydropyrimidine dehydrogenase deficiency.