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Colon CancerPhase 1/2NCT01985763

Genistein in Treatment of Metastatic Colorectal Cancer

A Phase 1/2 study testing Genistein in people with Colon Cancer and Rectal Cancer, run by Sofya Pintova at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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%. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colon Cancer, Rectal Cancer, Colorectal Cancer
What is being tested?
Genistein
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
Nov 2013to 31 Oct 2018
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 16Show fewer
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

Official title: Genistein Combined With FOLFOX or FOLFOX-Avastin for Treatment of Metastatic Colorectal Cancer: Phase I/II Pilot Study

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.

Read the 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)
Being tested
Genistein
Keywords
Genistein, soy supplements, phytoestrogens, colon cancer, rectal cancer, colorectal cancer, metastatic, stage IV, FOLFOX, FOLFOX-Avastin, Chemotherapy
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms, Colorectal Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GenisteinDrug

    Also called Bonistein

    Genistein combined with FOLFOX or FOLFOX-Avastin

Study groups in NCT01985763
Study groupRoleWhat they receive
GenisteinExperimentalGenistein 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.
Receives: Drug: Genistein

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: up to 6 months

  2. Percent Change in Tumor Size

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

    Measured: end of Cycle 6

Secondary outcomes (7)

  1. 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.

    Measured: end of Cycle 6

  2. 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

    Measured: up to 50 months

  3. 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.

    Measured: up to 50 months

  4. 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.

    Measured: up to 50 months

  5. 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.

    Measured: up to 50 months

  6. 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.

    Measured: 6 month and 12 month

  7. Overall Survival (OS)

    Overall Survival - Number of months still living since baseline

    Measured: up to 50 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Nov 2013 (estimated)
  2. Study startNov 2013
  3. Primary completion19 Jan 2017
  4. Study completion31 Oct 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01985763
Sponsor's protocol ID
GCO 13-1697
Status last verified
Apr 2019
First submitted
9 Nov 2013
Last updated
10 May 2019
Data monitoring committee
Yes

Publications

  • DeCosse JJ, Ngoi SS, Jacobson JS, Cennerazzo WJ. Gender and colorectal cancer. Eur J Cancer Prev. 1993 Mar;2(2):105-15. doi: 10.1097/00008469-199303000-00003.

    PubMed 8461861

  • Hebert-Croteau N. A meta-analysis of hormone replacement therapy and colon cancer in women. Cancer Epidemiol Biomarkers Prev. 1998 Aug;7(8):653-9.

    PubMed 9718216

  • Haenszel W, Berg JW, Segi M, Kurihara M, Locke FB. Large-bowel cancer in Hawaiian Japanese. J Natl Cancer Inst. 1973 Dec;51(6):1765-79. doi: 10.1093/jnci/51.6.1765. No abstract available.

    PubMed 4797262

  • Hu JF, Liu YY, Yu YK, Zhao TZ, Liu SD, Wang QQ. Diet and cancer of the colon and rectum: a case-control study in China. Int J Epidemiol. 1991 Jun;20(2):362-7. doi: 10.1093/ije/20.2.362.

    PubMed 1917235

  • Nishi M, Yoshida K, Hirata K, Miyake H. Eating habits and colorectal cancer. Oncol Rep. 1997 Sep-Oct;4(5):995-8. doi: 10.3892/or.4.5.995.

    PubMed 21590181

  • Kono S, Imanishi K, Shinchi K, Yanai F. Relationship of diet to small and large adenomas of the sigmoid colon. Jpn J Cancer Res. 1993 Jan;84(1):13-9. doi: 10.1111/j.1349-7006.1993.tb02777.x.

    PubMed 8449821

  • Witte JS, Longnecker MP, Bird CL, Lee ER, Frankl HD, Haile RW. Relation of vegetable, fruit, and grain consumption to colorectal adenomatous polyps. Am J Epidemiol. 1996 Dec 1;144(11):1015-25. doi: 10.1093/oxfordjournals.aje.a008872.

    PubMed 8942431

  • Pereira MA, Barnes LH, Rassman VL, Kelloff GV, Steele VE. Use of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agents. Carcinogenesis. 1994 May;15(5):1049-54. doi: 10.1093/carcin/15.5.1049.

    PubMed 8200067

  • 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

  • Thiagarajan DG, Bennink MR, Bourquin LD, Kavas FA. Prevention of precancerous colonic lesions in rats by soy flakes, soy flour, genistein, and calcium. Am J Clin Nutr. 1998 Dec;68(6 Suppl):1394S-1399S. doi: 10.1093/ajcn/68.6.1394S.

    PubMed 9848506

  • Li Y, Ahmed F, Ali S, Philip PA, Kucuk O, Sarkar FH. Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res. 2005 Aug 1;65(15):6934-42. doi: 10.1158/0008-5472.CAN-04-4604.

    PubMed 16061678

  • Linsalata M, Russo F, Notarnicola M, Guerra V, Cavallini A, Clemente C, Messa C. Effects of genistein on the polyamine metabolism and cell growth in DLD-1 human colon cancer cells. Nutr Cancer. 2005;52(1):84-93. doi: 10.1207/s15327914nc5201_11.

    PubMed 16091008

  • Qi W, Weber CR, Wasland K, Savkovic SD. Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity. BMC Cancer. 2011 Jun 3;11:219. doi: 10.1186/1471-2407-11-219.

    PubMed 21639915

  • Miyaki M, Konishi M, Kikuchi-Yanoshita R, Enomoto M, Igari T, Tanaka K, Muraoka M, Takahashi H, Amada Y, Fukayama M, et al. Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors. Cancer Res. 1994 Jun 1;54(11):3011-20.

    PubMed 8187091

  • Zhang Y, Chen H. Genistein attenuates WNT signaling by up-regulating sFRP2 in a human colon cancer cell line. Exp Biol Med (Maywood). 2011 Jun 1;236(6):714-22. doi: 10.1258/ebm.2011.010347. Epub 2011 May 13.

    PubMed 21571909

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Genistein in people with Colon Cancer and Rectal Cancer, run by Sofya Pintova at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Adverse Events (time frame: up to 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01985763, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2019.

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