Non Small Cell Lung CancerPhase 1/2NCT01628471
MTD Determination, Safety and Efficacy of the Decitabine-Genistein Drug Combination in Advanced Solid Tumors and Non-Small Cell Lung Cancer
A Phase 1/2 study testing decitabine in combination with genistein in people with Non Small Cell Lung Cancer, run by Uman Pharma at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- decitabine in combination with genistein
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2012to Sep 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 :
Show all 21Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- decitabine in combination with genistein
- Keywords
- Phase I b : advanced solid malignancy, Phase II a: stage III b or IV, Non Small Cell Lung Cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
decitabine in combination with genisteinDrug
decitabine IV infusion ( 10 hrs total), doses from 60 to 500 mg/m2 + fixed daily oral dose of 300 mg genisteine
| Study group | Role | What they receive |
|---|---|---|
| Decitabine + genistein single arm | Experimental | decitabine injectable, by infusion, 5 ascending doses (60 to 500 mg/m2) genisteine capsules, 3 x 50 mg capsules twice a day Receives: Drug: decitabine in combination with genistein |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
MTD determination will based on the incidence of reported adverse events (including dose-limiting toxicities) and abnormal laboratory test results.
Measured: 28 day treatment cycle for MTD assessment; 4-6 cycles to be administered
Secondary outcomes (2)
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.
Measured: Up to 6 , 28 day treatment 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)
Measured: Up to 6, 28 day treatment cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2012 (estimated)
- Study startNov 2012
- Primary completionMay 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uman Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- dsm-firmenich Switzerland AG, MDEIE Ministry, Québec Government, INRS-Institut Armand Frappier , Université du Québec
- Responsible party
- Sponsor
- Investigators
- Normand Blais, MD, FRCP(C), Principal investigator, Hôpital Notre Dame du CHUM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01628471
- Sponsor's protocol ID
- UMAN-10-01
- Status last verified
- Sep 2015
- First submitted
- 9 May 2012
- Last updated
- 23 Sep 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01628471
- Acronym / sponsor ID
- UMAN-10-01
- Conditions
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Uman PharmaIndustry (pharma, biotech, devices)
- Collaborators
- dsm-firmenich Switzerland AG, MDEIE Ministry, Québec Government, INRS-Institut Armand Frappier , Université du Québec
- Study start
- Nov 2012
- Primary completion
- May 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 26 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Decitabine + genistein single arm | Experimental | Drug: decitabine in combination with genisteindecitabine injectable, by infusion, 5 ascending doses (60 to 500 mg/m2) genisteine capsules, 3 x 50 mg capsules twice a day |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| decitabine in combination with genisteindecitabine IV infusion ( 10 hrs total), doses from 60 to 500 mg/m2 + fixed daily oral dose of 300 mg genisteine | Drug | Decitabine + genistein single arm |
Primary outcome
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.
2 secondary outcomes
To determine the drug plasma concentrations of decitabine and genistein.
Time frame: Up to 6 , 28 day treatment cycles
Preliminary clinical efficacy assessment
Time frame: Up to 6, 28 day treatment cycles
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2015.
- Study sponsorLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Normand Blais, MD, FRCP(C) principal investigator
Hôpital Notre Dame du CHUM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing decitabine in combination with genistein in people with Non Small Cell Lung Cancer, run by Uman Pharma at 1 site in Canada.
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 8 inclusion and 21 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 23 Sep 2015. 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 Canada. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum Tolerated Dose (MTD) (time frame: 28 day treatment cycle for MTD assessment; 4-6 cycles to be administered). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Sep 2015.