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

NCT01628471 | Completed Phase 1 DMC

• 1 other identifier: UMAN-10-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  MTD determination will based on the incidence of reported adverse events (including dose-limiting toxicities) and abnormal laboratory test results.

  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.

  Up to 6 , 28 day treatment cycles

• Preliminary clinical efficacy assessment

  Up to 6, 28 day treatment cycles

Study Arms (1)

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

Drug: decitabine in combination with genistein

Interventions

decitabine in combination with genistein DRUG

decitabine IV infusion ( 10 hrs total), doses from 60 to 500 mg/m2 + fixed daily oral dose of 300 mg genisteine

Decitabine + genistein single arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written Informed Consent.
• Males or females.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Uman Pharma: lead
• DSM Nutritional Products, Inc.: collaborator
• MDEIE Ministry, Québec Government: collaborator
• INRS-Institut Armand Frappier , Université du Québec: collaborator

Study Sites (1)

Hôpital Notre Dame du CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

Related Links

• Study sponsor

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Decitabine; Genistein

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Isoflavones; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Normand Blais, MD, FRCP(C)

  Hôpital Notre Dame du CHUM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2012
• First Posted: June 26, 2012
• Study Start: November 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: September 1, 2015
• Last Updated: September 23, 2015

Record last verified: 2015-09

Locations

CA (1)