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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
4SC AG
ClinicalTrials.gov Identifier:
NCT01344707
First received: April 12, 2011
Last updated: April 2, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Advanced Hematologic Malignancies
Drug: 4SC-202
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by 4SC AG:

Primary Outcome Measures:
  • Determination of Dose Limiting Toxicities of 4SC-202 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Determination of Safety of 4SC-202 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: Yes ]
  • Determination of Tolerability of 4SC-202 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Assessment of potential anticancer activity of 4SC-202 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
  • Histone acetylation in peripheral mononuclear cells [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Gene expression analysis in peripheral blood [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Cytokine and miRNA levels in plasma [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: March 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 4SC-202
    oral administration dose escalation twice daily (bid)or three times a day (tid) continuous dosing for 21 days per cycle
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01344707

Locations
Germany
Universiätsklinikum Köln
Köln, Germany
Robert-Bosch-Krankenhaus
Stuttgart, Germany
Universitätsklinikum Würzburg
Würzburg, Germany
Sponsors and Collaborators
4SC AG
Investigators
Principal Investigator: Andreas Engert, Prof. MD Universitätsklinikum Köln
  More Information

No publications provided

Responsible Party: 4SC AG
ClinicalTrials.gov Identifier: NCT01344707     History of Changes
Other Study ID Numbers: 4SC-202-1-2010
Study First Received: April 12, 2011
Last Updated: April 2, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by 4SC AG:
Hematologic Malignancies
Acute Myeloid Leukemia (AML)
Acute Lymphocytic Leukemia (ALL)
Chronic Lymphocytic Leukemia (CLL)
Multiple Myeloma (MM)
Myelodysplastic Syndrome (MDS)
Malignant Lymphomas
Histone Deacetylase (HDAC)
4SC-202
Phase I

Additional relevant MeSH terms:
Neoplasms
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014