Phase 1, Open-label Trial to Determine Safety of OPB-51602 in Subjects With Advanced Cancer

Phase 1, Open-label, Multiple Dose Escalation Trial to Determine Safety and Tolerability of Once-Daily OPB-51602 in Subjects With Advanced Cancer

The purpose of this study is to determine whether OPB-51602 is safe and tolerable when given daily by mouth to subjects with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: OPB-51602

Detailed Description

This study is based on data that support a role for the signal transducer and activator of transcription (STAT) family of proteins in oncogenesis. One of the mechanisms of action of OPB-51602 includes inhibition of STAT3 phosphorylation. Therefore OPB-51602 is expected to be active as an anti-cancer drug. This first-in-human study will characterize the safety profile of OPB-51602, evaluate the pharmacokinetics of OPB-51602, identify a recommended phase II dose, and obtain preliminary efficacy data, in subjects with advanced cancers for whom there is no standard treatment available.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Sarasota, Florida, United States, 34232
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
  • Tennessee
    • Nashville, Tennessee, United States, 37203

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects aged ≥ 18 years
2. Pathologically confirmed advanced cancer that is resistant or refractory to standard therapy or for which no standard curative therapy is available
3. At least 4 weeks since the last dose of prior chemotherapy, radiation therapy, or investigational agent.
4. Subjects must have recovered from adverse effects of prior therapy at time of enrollment to ≤ Grade 1 (excluding alopecia)
5. ECOG performance status ≤ 1
6. Life expectancy of ≥ 3 months following study entry

7. Adequate organ function, defined as follows:

   • Serum creatinine < 1.5 x the upper limit of normal (ULN)
   • Aspartate aminotransferase and alanine aminotransferase levels ≤ 3.0 x ULN (≤ 5.0 x ULN in the presence of known liver metastasis)
   • Total bilirubin ≤ 1.5 x ULN
   • Alkaline phosphatase levels ≤ 2.5 x ULN (≤ 5 x ULN in presence of bone metastasis)
   • Absolute neutrophil count of ≥ 1,500/mm³ (≥ 1.5 x 10⁹/L)
   • Platelet count ≥ 100,000/mm³ (≥ 100 x10⁹/L)
   • Hemoglobin ≥ 9 g/dL
8. For women of childbearing potential (WOCBP), a negative serum pregnancy test result at screening and negative urine pregnancy test on Day 1
9. WOCBP or men whose sexual partners are WOCBP must agree to use 2 methods of adequate contraception
10. Before any protocol-specific screening procedures are performed, subjects must have signed and dated the IRB-approved ICF.

Exclusion Criteria:

1. Uncontrolled concurrent illness, including ongoing or active infection, uncontrolled hypertension,or any other condition that could raise the subject's safety risk.
2. Altered mental status, psychiatric illness, or social situation that could limit compliance with study requirements and/or confound interpretation of study results.
3. Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C.
4. Known brain metastasis that has not been treated and stable for at least 4 weeks, or subjects with leptomeningeal disease.
5. Subjects unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with absorption of oral drugs.
6. A history of major surgery within 28 days of first receipt of study drug. Subjects must have recovered fully from any surgery.
7. Nursing or pregnant women
8. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in opinion of investigator, contraindicates use of an investigational drug, or that may render subject at excessively high risk for treatment complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OPDC-51602; Subjects with advanced solid tumors will be treated with OPDC-51602 once daily by mouth	Drug: OPB-51602; A cycle will consist of 28 days of OPB-51602 be taken by study subjects daily by mouth for every day of each 28 day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the safety and tolerability of OPB-51602	AEs, vital signs, body weight, ECGs, clinical laboratory tests, and performance status will be assessed.	Weekly for first cycle, then every 2 weeks (on average up to 8 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the pharmacokinetics of OPB-51602 and to determine the MTD of OPB-51602	The following PK parameters (Cmax, tmax, AUC₀-t, AUCtau, CLss/F and t½,z) will be determined using a non-compartmental approach for OPB-51602 and selected metabolites after single (Cycle 1, Day 1) and multiple daily doses (Cycle 2, Day 1).	28 days
Pharmacodynamic profile:	Study drug effects on STAT-3 phosphorylation will be assessed in PBMCs of study subjects in the dose escalation and expansion stages.	28 days
Antitumor effects:	Treatment response and/or disease progression in subjects with measurable disease will be evaluated after every 2 cycles using Response Evaluation Criteria in Solid Tumors (RECIST₉).	Every 2 cycles (on average 8 weeks).

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Investigators: Study Director: Agnes Elekes, M.D., Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: August 3, 2011
• First Submitted That Met QC Criteria: August 24, 2011
• First Posted (Estimate): August 26, 2011

Study Record Updates

• Last Update Posted (Estimate): January 15, 2014
• Last Update Submitted That Met QC Criteria: January 14, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Phase I; solid tumors; STAT-3 inhibitor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 266-09-202