Phase 1, Dose-escalation Trial of OPB-51602 in Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Beijing Research Institute
ClinicalTrials.gov Identifier:
NCT01184807
First received: August 17, 2010
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

This is an open-label, non-randomized, dose-escalation trial in patients with advanced solid tumors. The trial comprises 2 stages: a dose escalation stage at 8 dose levels of 2, 5, 10, 20, 40, 60, 80, and 100 mg/day,and possibly additional intermediate doses, to determine the MTD and recommended dose, and a subsequent 2 parts of expansion stage to investigate the safety profile and antitumor effect of OPB-51602 at the recommended dose.


Condition Intervention Phase
Malignant Solid Tumour
Drug: OPB-51602
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label, Non-randomized, Dose-escalation Trial of OPB-51602 in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Otsuka Beijing Research Institute:

Primary Outcome Measures:
  • safety and tolerability [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    AEs, vital signs, body weight, ECG, clinical laboratory tests, and ECOG performances status in the first cycle of treatment


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: duration of the treatment ] [ Designated as safety issue: No ]
    plasma and urinary concentrations of OPB-51602 and its metabolites

  • safety and tolerability [ Time Frame: duration of treatment ] [ Designated as safety issue: Yes ]
    AEs, vital signs, body weight, ECG, clinical laboratory tests, and ECOG performances status in all treatment cycles.

  • efficacy [ Time Frame: duration of treatment ] [ Designated as safety issue: No ]
    Response and progression evaluated using Response Evaluation criteria in solid tumors (RECIST)


Enrollment: 51
Study Start Date: December 2009
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
OPB-51602 Drug: OPB-51602
OPB-51602 at a dose of 2, 5, 10, 20, 40, 60, 80, or 100 mg/day,will be orally administered to subjects once daily for 2 weeks in each cycle of treatment in Dose Escalation Stage.A 2-day treatment-free interval will occur on Days 2 and 3 for PK sampling. Study drug administration will resume on Day 4 and continue until Day 17 in cycle 1.In Expansion stage part 1, OPB-51602 will be administered at recommend dose (4mg) for 3 weeks per cycle 9 2 weeks treatment and 1 week washout). There is also 2-day treatment free interval between Day 1 and Day 4 for PK sampling in cycle 1.In Expansion stage part 2, subject dosing will be started on Day 1 without 2-day treatment free interval and continued until Day 28 at recommend dose (4mg) first in Cycle 1. The same subjects will be treated at MTD(5mg)from cycle 2 onwards for 4 weeks per cycle.

Detailed Description:

In expansion stage part 1, up to 20 advanced sold tumor subjects will be investigated the safety profiled and antitumor effect of OPB-51602 at the recommended dose for 3 weeks per cycle(2 weeks treatment and 1 week washout). In the expansion stage part 2, a maximum of 20 subjects with Non-small cell lung cancer (NSCLC), Melanoma or Gastrointestinal Stromal Tumor (GIST) will be treated until an investigational Medicinal product (IMP) efficacious case can be found. subject dosing will be started on Day 1 without 2-day treatment free interval and continued until Day 28 at recommend dose (4mg) first in cycle 1. After safety and tolerability are confirmed, same subjects will be treated at the MTD(5mg) from cycle 2 onwards as a once-daily oral dose for 4 weeks per cycle to obtain additional information about safety, tolerability and antitumor activity of OPB-51602

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with pathologically confirmed, locally advanced or metastatic solid tumors who are unresponsive to standard therapy or for whom standard therapy is intolerable or unsuitable
  • Age: ≥21 years (at time of informed consent)
  • ECOG performance status: ≤2 (Appendix 1)
  • Life expectancy of longer than 3 months
  • Adequate vital organ function as follows:

    1. Bone marrow function Neutrophils: ≥1,500/μL, platelets: ≥75,000/μL, hemoglobin: ≥9.0 g/dL
    2. Hepatic function Aspartate transaminase (AST) and alanine transaminase(ALT): ≤2.5 ×institutional upper limit of normal(ULN) or ≤5.0 × institutional ULN if there is liver metastasis, serum total bilirubin: <2.5 × institutional ULN
    3. Renal function Serum creatinine: <1.5 × institutional ULN
  • Capable of swallowing OPB-51602 tablets
  • Ability to understand and willingness to sign written informed consent form (ICF) for participation in the trial
  • No chemotherapy, radiotherapy, surgery, immunotherapy, or other therapy within 4 weeks prior to start of investigational medicinal product (IMP) administration and recovered from any prior toxicity
  • If a subject has received more than 5 regimens of previous chemotherapy, the investigator must discuss with the sponsor regarding subject suitability prior to enrollment.

Exclusion Criteria:

  • Uncontrolled central nervous system (CNS) metastasis
  • Uncontrolled concurrent illness, including active infection, angina pectoris, cardiac arrhythmia, or heart failure (NYHA class III or IV, Appendix 2 New York Heart Association (NYHA) functional classification)
  • Concurrent malignancy of a different type
  • Immunocompromised subjects, including those who are known to be infected with human immunodeficiency virus (HIV)
  • Psychiatric illness that would limit compliance with trial requirements
  • Pregnant or breast-feeding women
  • Women of childbearing potential (WOCBP) or male subjects whose partners are WOCBP who cannot or will not use effective contraceptive measures
  • Administration of another investigational agent within 6 weeks prior to start of IMP administration
  • Use of any of the prohibited medications and other substances listed in Appendix 3 CYP3A4 Inhibitors and Inducers within either 1 week prior to start of IMP administration or a period of at least 5 times the respective elimination halflife, whichever is longer
  • Known severe gastrointestinal disorder, including malabsorption (at screening)
  • Patients with CTCAE Grade 1 or higher pneumonitis (interstitial pneumonia) or pulmonary fibrosis* * If interstitial lung abnormalities, (e.g. ground-glass or linear opacity) are suspected on chest CT scan (high-resolution CT), regardless of whether or not there are any accompanying symptoms it must be confirmed, such as through consultation with a respiratory or radiology expert if necessary, that the patient dose not fall under this exclusion criterion before the patient can be enrolled in the trial.
  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: NCT01184807

Locations
Singapore
National Cancer Centre, Department of Medical Oncology
Singapore, Singapore, 160610
National University Hospital (s) PTE LTD.
Singapore, Singapore, 119074
Sponsors and Collaborators
Otsuka Beijing Research Institute
Investigators
Principal Investigator: Goh Boon Cher, Dr Department of Haematology-Oncology,National University Hospital
Principal Investigator: Daniel Tan shao Weng, MD, PhD National Cancer Centre, Singapore
  More Information

No publications provided

Responsible Party: Otsuka Beijing Research Institute
ClinicalTrials.gov Identifier: NCT01184807     History of Changes
Other Study ID Numbers: 266-09-801-01
Study First Received: August 17, 2010
Last Updated: March 24, 2014
Health Authority: Singapore: Health Sciences Authority

Keywords provided by Otsuka Beijing Research Institute:
Advanced solid tumor

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on July 20, 2014