Quinacrine Hydrochloride and Capecitabine in Treating Patients with Metastatic or Recurrent Colorectal Cancer

Inclusion Criteria

• On primary diagnosis, patients must have had histologically confirmed adenocarcinoma of the colon or rectum; metastasis or recurrence do not need to be histologically confirmed
• Standard, curative or palliative measures do not exist or are no longer effective
• Patients must have measurable recurrence or metastases, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Patients must have prior chemotherapy for advanced CRC and have previously received both an oxaliplatin and an irinotecan based regimen; patients who are not appropriate for second line therapy because of their KRAS mutational status or because they cannot tolerate second line therapy, will be included even after only one prior therapy regimen
• All prior systemic cancer therapy (hormonal, chemotherapeutic, and immunotherapeutic) must be completed at least 4 weeks before the baseline visit
• Patients must be at least 4 weeks from radiation therapy or major surgery and have recovered from prior toxicities
• Life expectancy greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Leukocytes > 1,500/mcL
• Absolute neutrophil count > 1,500/mcL
• Platelets > 100,000/mcL
• Total bilirubin < 2.5 upper limit of normal (ULN)
• Aspartate transaminase (AST)/alanine transferase (ALT) < 3.0 ULN
• Creatinine < 2.0
• Creatinine clearance >= 50; creatinine clearance must be calculated using Cockroft-Gault formula
• Patient must be able to swallow capsules
• Patients must be able to understand and willing to sign a written informed consent document

Exclusion Criteria

• Patients may not be receiving any other investigational agents
• Patients who have had chemotherapy or radiotherapy 4 weeks or more prior to entering the study who’s adverse events have not recovered to grade 1 or less with the exception of alopecia and neuropathy
• Patients with known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to quinacrine, capecitabine or fluorouracil
• Patients receiving any medications or substances that are substrates, inducers, or inhibitors of cytochrome P450 2C9 (CYP2C9) enzyme
• 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 or breast feeding women are excluded from this study
• Patients currently being 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 (AICD) implanted
• Patients who have a history of noninfectious (toxic, autoimmune) hepatitis or alcoholism
• Patients with a lifetime history of porphyria or psoriasis
• Patients with documented glucose-6-phosphate dehydrogenase deficiency
• Patients with a history of seizure disorder (except infant febrile seizures)
• Patients with a lifetime history of dermatitis as an allergic/toxic reaction to any medication
• Patients with known dihydropyrimidine dehydrogenase (DPD) deficiency