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Trial record 93 of 1148 for:    Oral Cancer | ( Map: Canada )

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01628471
Recruitment Status : Completed
First Posted : June 26, 2012
Last Update Posted : September 23, 2015
DSM Nutritional Products, Inc.
MDEIE Ministry, Québec Government
INRS-Institut Armand Frappier , Université du Québec
Information provided by (Responsible Party):
Uman Pharma

Brief Summary:

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 or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: decitabine in combination with genistein Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : November 2012
Actual Primary Completion Date : May 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 :
  1. 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.

  2. 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)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
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.

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 identifier (NCT number): NCT01628471

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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
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Principal Investigator: Normand Blais, MD, FRCP(C) Hôpital Notre Dame du CHUM

Additional Information:
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Responsible Party: Uman Pharma Identifier: NCT01628471     History of Changes
Other Study ID Numbers: UMAN-10-01
First Posted: June 26, 2012    Key Record Dates
Last Update Posted: September 23, 2015
Last Verified: September 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:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Bronchial Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Estrogens, Non-Steroidal
Hormones, Hormone Substitutes, and Hormone Antagonists