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Genistein in Treatment of Metastatic Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT01985763
Recruitment Status : Completed
First Posted : November 15, 2013
Results First Posted : May 10, 2019
Last Update Posted : May 10, 2019
Sponsor:
Collaborator:
DSM Nutritional Products, Inc.
Information provided by (Responsible Party):
Sofya Pintova, Icahn School of Medicine at Mount Sinai

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.


Condition or disease Intervention/treatment Phase
Colon Cancer Rectal Cancer Colorectal Cancer Drug: Genistein Phase 1 Phase 2

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)

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Genistein Combined With FOLFOX or FOLFOX-Avastin for Treatment of Metastatic Colorectal Cancer: Phase I/II Pilot Study
Study Start Date : November 2013
Actual Primary Completion Date : January 19, 2017
Actual Study Completion Date : October 31, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Genistein

Arm Intervention/treatment
Experimental: Genistein
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
Genistein combined with FOLFOX or FOLFOX-Avastin
Other Name: Bonistein




Primary Outcome Measures :
  1. Number of Adverse Events [ Time Frame: up to 6 months ]
    Number of adverse events to assess tolerability of genistein treatment. Evaluation of side effects conducted every 14 days before each chemotherapy/genistein cycle.

  2. Percent Change in Tumor Size [ Time Frame: end of Cycle 6 ]
    Percent change in tumor size after cycle 6. Each cycle is 21 days.


Secondary Outcome Measures :
  1. Response Rate RECIST Criteria [ Time Frame: end of Cycle 6 ]

    Response Rate (RR) as measured by radiologic RECIST criteria. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

    Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

    Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.


  2. Number of Participants With an Overall Response Rate (ORR) [ Time Frame: up to 50 months ]
    Number of participants with an ORR - the portion of patients with a tumor size reduction of a predefined amount for a minimum time period

  3. Best Overall Response Rate RECIST Criteria [ Time Frame: up to 50 months ]

    Best Overall Response Rate (ORR) as measured by radiologic RECIST criteria. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.

    SD - target lesion SD, non target lesions Non-PD, and no new lesions. PR - target lesion CR, non target lesions Incomplete response/SD and no new lesions; or target lesion PR, non target lesions Non-PD, and no new lesions.

    PD - target lesions PD, non target lesions Any, can have new lesions; or target lesions Any, non target lesions PD, can have new lesions; or target lesions Any, non target lesions Any, have new lesions.


  4. Number of Participants With Best Overall Response Rate (ORR) [ Time Frame: up to 50 months ]
    The number of participants with best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.

  5. Progression Free Survival (PFS) [ Time Frame: up to 50 months ]
    Patients monitored for progression. Progression-free survival (PFS) is the length of time during and after the treatment that a patient lives with the disease but it does not get worse.

  6. Percent of Patients With Progression Free Survival (PFS) at 6 Months and 12 Months [ Time Frame: 6 month and 12 month ]

    Patients monitored for progression during the study period and 1 year following.

    Progression-free survival (PFS) is the length of time during and after the treatment that a patient lives with the disease but it does not get worse.


  7. Overall Survival (OS) [ Time Frame: up to 50 months ]
    Overall Survival - Number of months still living since baseline



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01985763


Locations
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United States, New York
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Sofya Pintova
DSM Nutritional Products, Inc.
Investigators
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Principal Investigator: Randall F Holcombe, MD Icahn School of Medicine at Mount Sinai
Principal Investigator: Sofya Pintova, MD Icahn School of Medicine at Mount Sinai
  Study Documents (Full-Text)

Documents provided by Sofya Pintova, Icahn School of Medicine at Mount Sinai:
Study Protocol  [PDF] September 12, 2016
Statistical Analysis Plan  [PDF] September 27, 2013


Publications:
Helms JR and Gallaher DD, The effect of dietary soy protein isolate and genistein on the development of preneoplastic lesions (aberrant crypts) in rats. 1995 Cancer Lett:125
Yanhong H, et al, Genistein sensitizes ovarian carcinoma cells to chemotherapy by switching the cell cycle progression in vitro. J Medical Colleges of PLA:125-135

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sofya Pintova, Assistant Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT01985763     History of Changes
Other Study ID Numbers: GCO 13-1697
First Posted: November 15, 2013    Key Record Dates
Results First Posted: May 10, 2019
Last Update Posted: May 10, 2019
Last Verified: April 2019

Keywords provided by Sofya Pintova, Icahn School of Medicine at Mount Sinai:
Genistein
soy supplements
phytoestrogens
colon cancer
rectal cancer
colorectal cancer
metastatic
stage IV
FOLFOX
FOLFOX-Avastin
Chemotherapy

Additional relevant MeSH terms:
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Colorectal Neoplasms
Rectal Neoplasms
Colonic Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Genistein
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Anticarcinogenic Agents
Protective Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Phytoestrogens
Estrogens, Non-Steroidal
Estrogens