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MTD Determination, Safety and Efficacy of the Decitabine-Genistein Drug Combination in Advanced Solid Tumors and Non-Small Cell Lung Cancer

This study has been completed.
DSM Nutritional Products, Inc.
MDEIE Ministry, Québec Government
INRS-Institut Armand Frappier , Université du Québec
Information provided by (Responsible Party):
Uman Pharma Identifier:
First received: May 9, 2012
Last updated: September 21, 2015
Last verified: September 2015

Lung cancer is one of the most prevalent and lethal neoplasias in the world. Currently used chemotherapy regimens have been disappointing in improving overall survival. Decitabine is a S-phase pyrimidine analog that induces DNA hypomethylation. This drug is currently used to treat Myelodysplastic Syndrome ( MDS) and has been studied for the treatment of leukemia. Genistein, is a soy extracted non-toxic isoflavone and phytoestrogen, which has been shown to inhibit activity of cell signaling pathways, such as those driven by tyrosine kinases. Results from in vitro experiments unambiguously demonstrated that the combination of these two compounds induces a synergistic reduction of the multiplication of lung, colon, breast and leukemic cancer cells. Consequently, clinical evaluation of this drug combination is warranted in Non Small Cell Lung Cancer ( NSCLC), and it is hypothezised that this new regimen will safely improve overall tumor response rate and cancer progression free survival.

The proposed trial is a two part study: The phase I part is an open-label, dose-escalation evaluation in subjects with advanced solid tumors who have failed standard therapies and for whom no curative therapeutic option exists.

A cohort of three subjects will be treated per dose level. One cycle is 28 days. Five different, increasing dose levels ranging from 60 mg/m2 to 500 mg/m2 of IV decitabine combined with a fixed oral dose of 150 mg BID of genistein will be tested. The Maximum Tolerated Dose (MTD) will be determined based on the occurrence of Dose Limiting Toxicities (DLTs).

In the phase IIa part of the study, only Stage IIIb and IV advanced NSCLC patients will be treated at the recommended decitabine MTD dose combined with genistein. Safety and preliminary efficacy will be assessed. It is expected that a maximum sample of 46 patients will be enrolled in this trial.

Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: decitabine in combination with genistein
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/IIa Dose-Escalation Study of the Decitabine-Genistein Drug Combination in Advanced Solid Tumors and Non-Small Cell Lung Cancer (NSCLC) Subjects

Resource links provided by NLM:

Further study details as provided by Uman Pharma:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 28 day treatment cycle for MTD assessment; 4-6 cycles to be administered ]
    MTD determination will based on the incidence of reported adverse events (including dose-limiting toxicities) and abnormal laboratory test results.

Secondary Outcome Measures:
  • To determine the drug plasma concentrations of decitabine and genistein. [ Time Frame: Up to 6 , 28 day treatment cycles ]
    Plasma drug levels will be used to obtain preliminary PK profile. Up to 11 blood samples to be obtained from each enrolled patient, over several cycles.

  • Preliminary clinical efficacy assessment [ Time Frame: Up to 6, 28 day treatment cycles ]
    Preliminary efficacy of the investigational regimen will include the assessment of Overall Response Rate ( ORR) and Progression Free Survival(PFS)

Enrollment: 20
Study Start Date: November 2012
Study Completion Date: September 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Decitabine + genistein single arm
decitabine injectable, by infusion, 5 ascending doses (60 to 500 mg/m2) genisteine capsules, 3 x 50 mg capsules twice a day
Drug: decitabine in combination with genistein
decitabine IV infusion ( 10 hrs total), doses from 60 to 500 mg/m2 + fixed daily oral dose of 300 mg genisteine


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Written Informed Consent.
  • Males or females.
  • 18-75 years.
  • Histologically or cytologically confirmed non-estrogen dependent advanced solid malignancy who has failed standard therapies and/or for which no curative therapeutic option exists (phase I) or ;
  • Histologically or cytologically confirmed NSCLC of stage IIIb or IV (phase IIa) that has failed or is ineligible to standard therapies.
  • One or more tumor lesions measurable by RECIST criteria
  • Life expectancy of at least 3 months.
  • ECOG performance of 2 or less.

Exclusion Criteria:

  • Prior decitabine or genistein therapy.
  • Received cytotoxic agent, hormonal therapy, radiation therapy, or other targeted cancer therapies or investigational agent within 4 weeks prior to study entry.
  • Patients with confirmed estrogen receptor-positive cancers, or patients with a primary breast or endometrial cancer for which phenotyping analysis has not been performed.
  • Presence of uncontrolled brain metastases or leptomeningeal disease.
  • Uncontrolled cardiovascular disorders, including symptomatic heart failure, unstable angina and cardiac arrhythmias.
  • Inadequate baseline organ function as shown by following laboratory values :

    • Hemoglobin < 90 g/L
    • Absolute neutrophil count < 1,500 /microliter
    • Platelet count < 100,000 /microliter
    • Total bilirubin > 1.5 ULN
    • AST and ALT > 2.5 ULN
    • Creatinine clearance < 60 ml/min
  • To be dependent of oxygen treatment.
  • Active infections requiring antibiotics.
  • Pregnancy or breastfeeding. All women of child-bearing potential must have a negative pregnancy test prior to first receiving protocol therapy.
  • Known allergic reactions to soy derivatives or deoxycytidine derivatives.
  • Active alcohol or drug abuse.
  • Any co-morbid condition that in the judgment of the investigator renders the subject at high risk of treatment complication or reduces the probability of assessing clinical effect.
  • Other malignancies diagnosed within the last 5 years with the exception of Basal Cell Carcinoma of the skin.
  • Gastrointestinal disorders or abnormalities that may interfere with the absorption of genistein.
  • Patients unable to comply with the study protocol and follow-up schedule for any psychological, familial, sociological or geographical reason.
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Please refer to this study by its identifier: NCT01628471

Canada, Quebec
Hôpital Notre Dame du CHUM
Montreal, Quebec, Canada, H2L 4M1
Sponsors and Collaborators
Uman Pharma
DSM Nutritional Products, Inc.
MDEIE Ministry, Québec Government
INRS-Institut Armand Frappier , Université du Québec
Principal Investigator: Normand Blais, MD, FRCP(C) Hôpital Notre Dame du CHUM
  More Information

Additional Information:
Responsible Party: Uman Pharma Identifier: NCT01628471     History of Changes
Other Study ID Numbers: UMAN-10-01
Study First Received: May 9, 2012
Last Updated: September 21, 2015

Keywords provided by Uman Pharma:
Phase I b : advanced solid malignancy
Phase II a: stage III b or IV, Non Small Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogens, Non-Steroidal
Hormones, Hormone Substitutes, and Hormone Antagonists
Antimetabolites, Antineoplastic
Antimetabolites processed this record on April 28, 2017