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Oral Histone Deacetylase Inhibitor 4SC-202 in Patients With Advanced Hematologic Malignancies (TOPAS)

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ClinicalTrials.gov Identifier: NCT01344707
Recruitment Status : Completed
First Posted : April 29, 2011
Last Update Posted : April 1, 2015
Sponsor:
Information provided by (Responsible Party):
4SC AG

Tracking Information
First Submitted Date  ICMJE April 12, 2011
First Posted Date  ICMJE April 29, 2011
Last Update Posted Date April 1, 2015
Study Start Date  ICMJE March 2011
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2013)
  • Determination of Dose Limiting Toxicities of 4SC-202 [ Time Frame: 6 weeks ]
  • Determination of Safety of 4SC-202 [ Time Frame: 6 weeks ]
    The safety and tolerability will be determined by occurrence of adverse events (AEs), vital signs (VS) [body temperature, weight, blood pressure (BP), pulse rate], electrocardiogram (ECG), performance status and clinical laboratory parameters.
  • Determination of Pharmacokinetic Profile of 4SC-202 [ Time Frame: 3 weeks ]
    The plasma concentrations of 4SC-202 will be determined at the following time-points: Cycle 1 Day 1: Pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 8 h, 24 h p.a. Cycle 1 Day 5: Pre-dose, 0.5 h, 1h, 2h Cycle 1 Day 14: Pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 8 h, 24 h p.a. Cycle 2 Day 1: Pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 8 h, 24 h p.a. using AUC0-infinity, AUClast, Cmax, tmax, t1/2, CL/F
  • Determination of Maximum Tolerated Dose of 4SC-202 [ Time Frame: 6 weeks ]
  • Determination of Tolerability of 4SC-202 [ Time Frame: 6 weeks ]
    The safety and tolerability will be determined by occurrence of adverse events (AEs), vital signs (VS) [body temperature, weight, blood pressure (BP), pulse rate], electrocardiogram (ECG), performance status and clinical laboratory parameters.
Original Primary Outcome Measures  ICMJE
 (submitted: April 28, 2011)
  • Determination of Dose Limiting Toxicities of 4SC-202 [ Time Frame: 6 weeks ]
  • Determination of Safety of 4SC-202 [ Time Frame: 6 weeks ]
    The safety and tolerability will be determined by occurance of adverse events (AEs), vital signs (VS) [body temperature, weight, blood pressure (BP), pulse rate], electrocardiogram (ECG), performance status and clinical laboratory parameters.
  • Determination of Pharmacokinetic Profile of 4SC-202 [ Time Frame: 3 weeks ]
    The plasma concentrations of 4SC-202 will be determined at the following time-points: Cycle 1 Day 1: Pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 8 h, 24 h p.a. Cycle 1 Day 5: Pre-dose Cycle 1 Day 14: Pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 8 h, 24 h p.a. Cycle 2 Day 1: Pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 8 h, 24 h p.a. using AUC0-24, AUC0-infinity, AUClast, Cmax, tmax, t1/2, CL/F
  • Determination of Maximum Tolerated Dose of 4SC-202 [ Time Frame: 6 weeks ]
  • Determination of Tolerability of 4SC-202 [ Time Frame: 6 weeks ]
    The safety and tolerability will be determined by occurance of adverse events (AEs), vital signs (VS) [body temperature, weight, blood pressure (BP), pulse rate], electrocardiogram (ECG), performance status and clinical laboratory parameters.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2013)
  • Assessment of potential anticancer activity of 4SC-202 [ Time Frame: 6 weeks ]
    The assessment will be performed by assessment of tumor response, duration of response and progression free survival
  • Histone deacetylase (HADAC) inhibition in peripheral mononuclear cells [ Time Frame: 6 weeks ]
  • Histone acetylation in peripheral mononuclear cells [ Time Frame: 6 weeks ]
  • Gene expression analysis in peripheral blood [ Time Frame: 6 weeks ]
  • Cytokine and miRNA levels in plasma [ Time Frame: 6 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2011)
  • Assessment of potential anticancer activity of 4SC-202 [ Time Frame: 6 weeks ]
    The assessment will be performed by assessment of tumor response, duration of response and progression free survival
  • Histone deacetylase (HADAC) inhibition in peripheral mononuclear cells [ Time Frame: 6 weeks ]
  • Histone acetylation in peripheral mononuclear cells [ Time Frame: 6 weeks ]
  • Gene expression analysis in peripheral blood [ Time Frame: 6 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oral Histone Deacetylase Inhibitor 4SC-202 in Patients With Advanced Hematologic Malignancies (TOPAS)
Official Title  ICMJE Open Label, Dose Escalation Study of 4SC-202 in Patients With Advanced Hematologic Malignancies: First-In-Man Study of a Newly Developed, Oral Histone Deacetylase Inhibitor
Brief Summary The purpose of this study is to determine the Maximum Tolerated Dose, Dose Limiting Toxicities and optimal dosing schedule of 4SC-202 investigating its safety, tolerability and pharmacokinetics.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Hematologic Malignancies
Intervention  ICMJE Drug: 4SC-202
oral administration dose escalation twice daily (bid)or three times a day (tid) continuous dosing for 21 days per cycle
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: April 28, 2011)
36
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2015
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female patients, age ≥ 18 years.
  • Patients with Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM),Myelodysplastic Syndrome (MDS) or malignant lymphoma which are relapsed and/or refractory to standard therapy or for which no standard therapy exists. Patients who are not eligible for curative stem cell transplantation or patients who have refused or are not eligible for frontline (chemo-) therapy may also be included.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
  • Patients must have a live expectancy of 12 weeks or more.
  • Patients must have adequate bone marrow reserve as well as adequate renal and hepatic function and serum electrolytes within a clinically acceptable range.
  • Patients must have recovered from any treatment-related toxicities (to Grade 0 or 1 according to Common Terminology Criteria for Adverse Events (CTCAE); except for alopecia, fatigue and Grade 1 neurotoxicity) prior to registration.

Exclusion Criteria:

  • Patients who have received previous treatment with an HDAC inhibitor.
  • Patients with any gastrointestinal disorder that could interfere with the absorption of 4SC-202
  • Patients who are unable to take oral medication.
  • Patients with a history of other malignancies unless having undergone definitive treatment more than 5 years prior to entry into the study and without evidence of recurrent malignant disease, excluding patients with basal cell carcinoma of the skin; superficial carcinoma of the bladder; carcinoma of the prostate with a current prostate specific antigen (PSA) value of < 0.1 ng/ml; or cervical intraepithelial neoplasia.
  • Patients with a history of, who were treated for, or who are suspected of having, hepatitis B, hepatitis C or human immunodeficiency virus (HIV). Patients suspected of having any of these conditions should undergo appropriate evaluations prior to being enrolled in the study.
  • Patients with precedent anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the last two weeks or a longer period depending on the known PK characteristics of the agents used.
  • Patients with history or current evidence of clinically relevant allergies or idiosyncrasy to drugs (especially of similar chemical composition to the study drug) or food.
  • Patients with symptomatic brain metastases/central nervous system (CNS) involvement.
  • Patients with significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure (New York Heart Association (NYHA) Class III or IV) related to primary cardiac disease, a condition requiring anti-arrhythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry.
  • Patients with a marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 450 msec (Grade 1 CTCAE); Long-QT-Syndrome; the required use of concomitant medication on 4SC-202 dosing days that may cause Torsade de Pointes.
  • Therapy with agents known to prolong the QT interval, such as certain antibiotics (i.e. erythromycin, clarithromycin), antidepressants (i.e. doxepin, amitryptilin) or neuroleptics (i.e. haloperidol, clozapin).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01344707
Other Study ID Numbers  ICMJE 4SC-202-1-2010
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party 4SC AG
Study Sponsor  ICMJE 4SC AG
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andreas Engert, Prof. MD Universitätsklinikum Köln
PRS Account 4SC AG
Verification Date January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP