Clinical trial NCT01985763: Genistein in Treatment of Metastatic Colorectal Cancer
Official title: Genistein Combined With FOLFOX or FOLFOX-Avastin for Treatment of Metastatic Colorectal Cancer: Phase I/II Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colon Cancer
Rectal Cancer
Colorectal Cancer
Keywords: Genistein
soy supplements
phytoestrogens
colon cancer
rectal cancer
colorectal cancer
metastatic
stage IV
FOLFOX
FOLFOX-Avastin
Chemotherapy
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: DSM Nutritional Products, Inc.
First posted: 2013-11-15
Enrollment: 13
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: 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.

Detailed description: 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)

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Adverse Events
timeFrame: up to 6 months
measure: Percent Change in Tumor Size
timeFrame: end of Cycle 6
Secondary outcomes:
measure: Response Rate RECIST Criteria
timeFrame: end of Cycle 6
measure: Number of Participants With an Overall Response Rate (ORR)
timeFrame: up to 50 months
measure: Best Overall Response Rate RECIST Criteria
timeFrame: up to 50 months
measure: Number of Participants With Best Overall Response Rate (ORR)
timeFrame: up to 50 months
measure: Progression Free Survival (PFS)
timeFrame: up to 50 months
measure: Percent of Patients With Progression Free Survival (PFS) at 6 Months and 12 Months
timeFrame: 6 month and 12 month
measure: Overall Survival (OS)
timeFrame: up to 50 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Randall F Holcombe, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Sofya Pintova, MD
role: PRINCIPAL_INVESTIGATOR
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