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Genistein in Treatment of Metastatic Colorectal Cancer

Primary Purpose

Colon Cancer, Rectal Cancer, Colorectal Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Genistein

About this trial

This is an interventional treatment trial for Colon Cancer focused on measuring Genistein, soy supplements, phytoestrogens, colon cancer, rectal cancer, colorectal cancer, metastatic, stage IV, FOLFOX, FOLFOX-Avastin, Chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Genistein

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Percent Change in Tumor Size

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

Secondary Outcome Measures

Response Rate RECIST Criteria

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)

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

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)

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)

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

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)

Overall Survival - Number of months still living since baseline

Full Information

NCT ID

NCT01985763

First Posted

November 9, 2013

Last Updated

April 18, 2019

Sponsor

Sofya Pintova

Collaborators

DSM Nutritional Products, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01985763

Brief Title

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

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

November 2013 (undefined)

Primary Completion Date

January 19, 2017 (Actual)

Study Completion Date

October 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Sofya Pintova

Collaborators

DSM Nutritional Products, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colon Cancer, Rectal Cancer, Colorectal Cancer

Keywords

Genistein, soy supplements, phytoestrogens, colon cancer, rectal cancer, colorectal cancer, metastatic, stage IV, FOLFOX, FOLFOX-Avastin, Chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Genistein

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Genistein

Other Intervention Name(s)

Bonistein

Intervention Description

Genistein combined with FOLFOX or FOLFOX-Avastin

Primary Outcome Measure Information:

Title

Number of Adverse Events

Description

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

Time Frame

up to 6 months

Title

Percent Change in Tumor Size

Description

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

Time Frame

end of Cycle 6

Secondary Outcome Measure Information:

Title

Response Rate RECIST Criteria

Description

Time Frame

end of Cycle 6

Title

Number of Participants With an Overall Response Rate (ORR)

Description

Number of participants with an ORR - the portion of patients with a tumor size reduction of a predefined amount for a minimum time period

Time Frame

up to 50 months

Title

Best Overall Response Rate RECIST Criteria

Description

Time Frame

up to 50 months

Title

Number of Participants With Best Overall Response Rate (ORR)

Description

Time Frame

up to 50 months

Title

Progression Free Survival (PFS)

Description

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.

Time Frame

up to 50 months

Title

Percent of Patients With Progression Free Survival (PFS) at 6 Months and 12 Months

Description

Time Frame

6 month and 12 month

Title

Overall Survival (OS)

Description

Overall Survival - Number of months still living since baseline

Time Frame

up to 50 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 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 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Randall F Holcombe, MD

Organizational Affiliation

Icahn School of Medicine at Mount Sinai

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Sofya Pintova, MD

Organizational Affiliation

Icahn School of Medicine at Mount Sinai

Official's Role

Principal Investigator

Facility Information:

Facility Name

Icahn School of Medicine at Mount Sinai

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

12. IPD Sharing Statement

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Genistein in Treatment of Metastatic Colorectal Cancer

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