Genistein in Treatment of Metastatic Colorectal Cancer

Genistein Combined With FOLFOX or FOLFOX-Avastin for Treatment of Metastatic Colorectal Cancer: Phase I/II Pilot Study

Colorectal neoplasms are the third most common malignancies in the United States. Patients with metastatic (stage IV) colorectal cancer have a median life expectancy of 2 years. The response rates to chemotherapy range from 35-40%.

Epidemiologic evidence suggests that soy compounds may reduce the incidence of colorectal cancers. Laboratory analyses demonstrate that genistein, a soy-derived compound, may inhibit Wnt signaling, a pathway activated in majority of colorectal cancers. Laboratory observations also demonstrate that genistein may augment growth inhibition when combined with chemotherapeutic agents of 5-Fluorouracil and platinum compounds.

Based on pre-clinical data the investigators hypothesize that combining genistein with the standard of care chemotherapeutic regimens will reduce chemotherapy resistance and improve response rates in patients. The aim of the study is to add genistein to the regimens of FOLFOX or FOLFOX-Avastin in patients with newly diagnosed stage IV colon or rectal neoplasms.

OBJECTIVES:

Primary

• Evaluate the tolerability of genistein when combined with chemotherapy

Secondary:

• Evaluate Response Rate (RR) as measured by the radiologic RECIST criteria
• Evaluate Progression Free Survival (PFS)

Inclusion Criteria:

• Adult male and female patients ≥18 years old

• Have pathologically confirmed colon or rectal carcinoma

• Have metastatic (stage IV) disease

• Have a plan by treating physician to receive FOLFOX or FOLFOX-Avastin

• Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2

• Have adequate hematopoietic, hepatic and renal function

  1. Hematopoietic function

     • Hemoglobin ≥10g/dL
     • Absolute Neutrophil Count(ANC) ≥1,500cells/mm2
     • Platelet Count ≥100,000/µL

  2. Hepatic Function

     • Total bilirubin ≤ 1.5x the upper limit of normal
     • ALT and AST must each be ≤2,5x the upper limits of normal

  3. Renal Function

     • Estimated creatinine clearance (Clcr) ≥30 mL/minute

• Are not pregnant and do not plan to become pregnant

Exclusion Criteria:

• Prior systemic chemotherapy for metastatic disease
• History of breast cancer, endometrial cancer or ovarian cancer or taking aromatase inhibitors or selective estrogen receptor modulators
• Patients taking MAO-inhibitors
• History of myocardial infarctions or cardiac stent placement less than 1 year before recruitment into the study
• Unable to give informed consent or comply with clinical trial requirements
• Uncontrolled hypertension
• History of clinically significant GI bleeding within prior 2 months prior to enrollment
• Presence of GI fistula
• Prior history of bowel perforation
• History of CNS thrombotic/embolic or ischemic events
• Have past or current, acute or chronic concurrent medical condition/illness or therapy that, in the opinion of the investigator, would make the subject unsuitable for the clinical trial or unable to comply with the follow up visits.