Genistein in Treatment of Metastatic Colorectal Cancer

NCT01985763 | Completed Phase 1 Results DMC

• 1 other identifier: GCO 13-1697
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• Number of Adverse Events

  Number of adverse events to assess tolerability of genistein treatment. Evaluation of side effects conducted every 14 days before each chemotherapy/genistein cycle.

  up to 6 months

• Percent Change in Tumor Size

  Percent change in tumor size after cycle 6. Each cycle is 21 days.

  end of Cycle 6

Secondary Outcomes (7)

• Response Rate RECIST Criteria

  end of Cycle 6

• Number of Participants With an Overall Response Rate (ORR)

  up to 50 months

• Best Overall Response Rate RECIST Criteria

  up to 50 months

• Number of Participants With Best Overall Response Rate (ORR)

  up to 50 months

• Progression Free Survival (PFS)

  up to 50 months

Study Arms (1)

Genistein

EXPERIMENTAL

Genistein combined with FOLFOX or FOLFOX-Avastin Genistein 60mg/day orally for 7 days every 2 weeks. Genistein will be administered beginning 4 days prior to FOLFOX or FOLFOX-Avastin and continuing the 3 days of chemotherapy.

Drug: Genistein

Interventions

Genistein DRUG

Genistein combined with FOLFOX or FOLFOX-Avastin

Also known as: Bonistein

Genistein

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Hematopoietic function
• Hemoglobin ≥10g/dL
• Absolute Neutrophil Count(ANC) ≥1,500cells/mm2
• Platelet Count ≥100,000/µL
• Hepatic Function
• Total bilirubin ≤ 1.5x the upper limit of normal
• ALT and AST must each be ≤2,5x the upper limits of normal
• Renal Function
• Estimated creatinine clearance (Clcr) ≥30 mL/minute

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sofya Pintova: lead
• DSM Nutritional Products, Inc.: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (26)

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  BACKGROUND

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  PMID: 31203390 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis

Interventions

Genistein

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Isoflavones; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Sofya Pintova
• Organization: Icahn School of Medicine at Mount Sinai

Sofya.Pintova@mountsinai.org

212-824-8461

Study Officials

• Randall F Holcombe, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Sofya Pintova, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 9, 2013
• First Posted: November 15, 2013
• Study Start: November 1, 2013
• Primary Completion: January 19, 2017
• Study Completion: October 31, 2018
• Last Updated: May 10, 2019
• Results First Posted: May 10, 2019

Record last verified: 2019-04

Locations

US (1)