Back to resultsMTD Determination, Safety and Efficacy of the Decitabine-Genistein Drug Combination in Advanced Solid Tumors and Non-Small Cell Lung Cancer
Primary Purpose
Non Small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
decitabine in combination with genistein
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring Phase I b : advanced solid malignancy, Phase II a: stage III b or IV, Non Small Cell Lung Cancer
Eligibility Criteria
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.
Sites / Locations
- Hôpital Notre Dame du CHUM
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Decitabine + genistein single arm
Arm Description
decitabine injectable, by infusion, 5 ascending doses (60 to 500 mg/m2) genisteine capsules, 3 x 50 mg capsules twice a day
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose (MTD)
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.
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
Preliminary efficacy of the investigational regimen will include the assessment of Overall Response Rate ( ORR) and Progression Free Survival(PFS)
Full Information
NCT ID
NCT01628471
First Posted
May 9, 2012
Last Updated
September 21, 2015
Sponsor
Uman Pharma
Collaborators
DSM Nutritional Products, Inc., MDEIE Ministry, Québec Government, INRS-Institut Armand Frappier , Université du Québec
1. Study Identification
Unique Protocol Identification Number
NCT01628471
Brief Title
MTD Determination, Safety and Efficacy of the Decitabine-Genistein Drug Combination in Advanced Solid Tumors and Non-Small Cell Lung Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Uman Pharma
Collaborators
DSM Nutritional Products, Inc., MDEIE Ministry, Québec Government, INRS-Institut Armand Frappier , Université du Québec
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer
Keywords
Phase I b : advanced solid malignancy, Phase II a: stage III b or IV, Non Small Cell Lung Cancer
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
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Decitabine + genistein single arm
Arm Type
Experimental
Arm Description
decitabine injectable, by infusion, 5 ascending doses (60 to 500 mg/m2) genisteine capsules, 3 x 50 mg capsules twice a day
Intervention Type
Drug
Intervention Name(s)
decitabine in combination with genistein
Intervention Description
decitabine IV infusion ( 10 hrs total), doses from 60 to 500 mg/m2 + fixed daily oral dose of 300 mg genisteine
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD)
Description
MTD determination will based on the incidence of reported adverse events (including dose-limiting toxicities) and abnormal laboratory test results.
Time Frame
28 day treatment cycle for MTD assessment; 4-6 cycles to be administered
Secondary Outcome Measure Information:
Title
To determine the drug plasma concentrations of decitabine and genistein.
Description
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.
Time Frame
Up to 6 , 28 day treatment cycles
Title
Preliminary clinical efficacy assessment
Description
Preliminary efficacy of the investigational regimen will include the assessment of Overall Response Rate ( ORR) and Progression Free Survival(PFS)
Time Frame
Up to 6, 28 day treatment cycles
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Normand Blais, MD, FRCP(C)
Organizational Affiliation
Hôpital Notre Dame du CHUM
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Notre Dame du CHUM
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
12. IPD Sharing Statement
Links:
URL
http://www.umanpharma.com
Description
Study sponsor
Learn more about this trial
MTD Determination, Safety and Efficacy of the Decitabine-Genistein Drug Combination in Advanced Solid Tumors and Non-Small Cell Lung Cancer
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