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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

Tracking Information
First Submitted Date  ICMJE November 9, 2013
First Posted Date  ICMJE November 15, 2013
Results First Submitted Date  ICMJE March 26, 2019
Results First Posted Date  ICMJE May 10, 2019
Last Update Posted Date May 10, 2019
Study Start Date  ICMJE November 2013
Actual Primary Completion Date January 19, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
  • 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.
  • Percent Change in Tumor Size [ Time Frame: end of Cycle 6 ]
    Percent change in tumor size after cycle 6. Each cycle is 21 days.
Original Primary Outcome Measures  ICMJE
 (submitted: November 14, 2013)
tolerability of genistein treatment [ Time Frame: up to 6 months ]
Evaluation of side effects will be conducted every 14 days before each chemotherapy/genistein cycle. Side effects will be evaluated by a brief survey.
Change History Complete list of historical versions of study NCT01985763 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2019)
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • Overall Survival (OS) [ Time Frame: up to 50 months ]
    Overall Survival - Number of months still living since baseline
Original Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2013)
  • Response Rate (RR) CEA [ Time Frame: up to 18 months ]
    Response Rate (RR) as measured by radiologic RECIST criteria. Restaging will be done by the treating physician as part of standard of care. CEA and radiographic restaging maybe triggered by clinical changes or routine follow up. Standard of care is CEA every 6 weeks.
  • Response Rate (RR) imaging [ Time Frame: up to 18 months ]
    Response Rate (RR) as measured by radiologic RECIST criteria. Restaging will be done by the treating physician as part of standard of care. CEA and radiographic restaging maybe triggered by clinical changes or routine follow up. Standard of care is radiographic imaging every 3 months.
  • Progression Free Survival (PFS) [ Time Frame: up to 18 months ]
    Patients will be monitored for progression during the study period and 1 year following.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Genistein in Treatment of Metastatic Colorectal Cancer
Official Title  ICMJE Genistein Combined With FOLFOX or FOLFOX-Avastin for Treatment of Metastatic Colorectal Cancer: Phase I/II Pilot Study
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)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Colon Cancer
  • Rectal Cancer
  • Colorectal Cancer
Intervention  ICMJE Drug: Genistein
Genistein combined with FOLFOX or FOLFOX-Avastin
Other Name: Bonistein
Study Arms  ICMJE 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.
Intervention: Drug: Genistein
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 25, 2017)
13
Original Estimated Enrollment  ICMJE
 (submitted: November 14, 2013)
24
Actual Study Completion Date  ICMJE October 31, 2018
Actual Primary Completion Date January 19, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01985763
Other Study ID Numbers  ICMJE GCO 13-1697
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sofya Pintova, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Sofya Pintova
Collaborators  ICMJE DSM Nutritional Products, Inc.
Investigators  ICMJE
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
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP