A Clinical Trial to Determine the Most Suitable Dose of OPB-111001 in Patients With Advanced Cancer

A Two-part Phase 1/2a, Open-label, Dose Escalation Study to Evaluate the Tolerability and Preliminary Antitumour Activity of OPB-111001 in Patients With Advanced Cancers That Are Poorly Responsive to Standard Anticancer Treatment

The purpose of this study is to determine the tolerability profile of OPB-111001 and to determine the most suitable dose of OPB-111001 in patients with advanced cancer

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Ovarian Cancer; Prostate Cancer; Endometrial Cancer; Salivary Gland Cancer; Squamous Cell Carcinoma of the Cervix
• Intervention / Treatment: Drug: OPB-111001

• Study Type: Interventional
• Enrollment (Anticipated): 79
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • NIHR/Wellcome Trust Imperial CRF/Imperial College Healthcare NHS Trust, Imperial Centre for Translational and Experimental Medicine (L-Block), Hammersmith Hospital
  • Surrey
    • London, Sutton, Surrey, United Kingdom, SM2 5PT
      • The Institute of Cancer Research, Royal Marsden NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 years of age
• Patients with prostate cancer that is recurrent or did not respond to previous hormone therapy and/or who have exhausted standard treatment options.

For the dose escalation parts only:

Patients who have exhausted standard treatment options with recurrent or refractory cancer (ovarian cancer, cervical squamous cell carcinoma, breast cancer, salivary gland cancer, endometrial cancer)

• Histologically or cytologically documented diagnosis of cancer
• Measurable disease according to RECIST Version 1.1 or for prostate cancer also evaluable disease according to Prostate Cancer Working Group 2 (PCWG2) eligibility criteria or for ovarian cancer also evaluable disease (non-measurable) according to Gynaecologic Cancer Intergroup (GCIG) criteria
• Absolute neutrophil count ≥1.5 (1500/mm3) and platelets ≥100 × 109/L (without platelet transfusion within the last 4 weeks before first study drug administration), and haemoglobin ≥9 g/dL at Screening
• Alanine aminotransferase and aspartate aminotransferase ≤2.5 × the upper limit of normal (ULN), Total bilirubin ≤1.5 × ULN (exception: patients with liver metastasis are allowed to have aspartate aminotransferase ≤5 × ULN and alanine aminotransferase ≤5 × ULN) at screening
• Albumin ≥26 g/L at Screening

Exclusion Criteria:

• Concurrent prior treatment-related toxicity of Grade 2 or higher. Exception: any toxicity that is in the view of the investigator not a clinically significant safety risk for Investigational medicinal product (IMP) administration.
• Previous treatment with cytotoxic chemotherapy or other anticancer therapy within 4 weeks before the first dosing with study drug (at least 6 weeks for mitoxantrone, nitrosurea, and bicalutamide).

• Treatment with systemic glucocorticosteroids of more than a 2 mg dexamethasone equivalent per day or in cases of treatment with ≤2 mg dexamethasone equivalent per day:

  1. Dosing was changed within 6 weeks before Screening or
  2. The patient's cancer is responding to glucocorticosteroid intake
• Radiation therapy within 4 weeks prior to the first dosing with IMP.
• Treatment with a systemic IMP in a clinical trial within 28 days before the Screening Visit.
• Current or past history of clinically significant gastrointestinal disease or major gastrointestinal surgery, malabsorption syndrome, or other conditions that could interfere with enteral absorption.
• Concurrent clinically significant unrelated systemic illness (e.g., serious infection) or significant pulmonary, hepatic, or other organ dysfunction that would compromise the patient's ability to tolerate study treatment or would likely interfere with study procedures or results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1: Regimen A Escalation; 1: OPB-111001, orally, once weekly	Drug: OPB-111001
Experimental: 2: Regimen A Extension; 2: OPB-111001, orally, once weekly	Drug: OPB-111001
Experimental: 3: Regimen B Escalation; 3: OPB-111001, orally, 2 - 3 times per week	Drug: OPB-111001
Experimental: 4: Regimen B Extension; 4: OPB-111001, orally, 2 - 3 times per week	Drug: OPB-111001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose / Recommended Phase 2 dose; Tolerability	after 2 or 6 weeks depending on study part; continously

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters for OPB-111001 and its metabolites	Frequent sampling during Cycle 1 to 3, D1 only from Cycle 4 onwards	repeatedly until end of study (average of 3 months assumed)
Assessment of antitumor activity as defined by Response Evaluation Criteria in Solid Tumours (RECIST)		repeatedly every 8th week until end of study (average of 3 months assumed)
Prostate-specific antigen (PSA) response in patients with prostate cancer		repeatedly (Cycle 1 to 3 on Day 1, then every 4th week) until end of study (average of 3 months assumed)
Cancer antigen 125 (CA 125) response in patients with ovarian cancer		repeatedly (Cycle 1 to 3 on Day 1, then every 4th week) until end of study (average of 3 months assumed)
Time to treatment failure		At end of study (after average of 3 months assumed)

Collaborators and Investigators

• Sponsor: Otsuka Novel Products GmbH
• Investigators: Principal Investigator: Johann De Bono, Prof. Dr., The Institute of Cancer Research, Royal Marsden NHS Foundation Trust London United Kingdom; Principal Investigator: Sarah Blagden, Dr., NIHR/Wellcome Trust Imperial CRF, Imperial College Healthcare NHS Trust, Imperial Center for Translational and Experimental Medicine (L-Block), Hammersmith Hospital London, United Kingdom

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: January 17, 2014
• First Submitted That Met QC Criteria: January 20, 2014
• First Posted (Estimate): January 23, 2014

Study Record Updates

• Last Update Posted (Estimate): October 20, 2015
• Last Update Submitted That Met QC Criteria: October 19, 2015
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Genital Neoplasms, Male; Prostatic Diseases; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Mouth Neoplasms; Prostatic Neoplasms; Endometrial Neoplasms; Salivary Gland Neoplasms
• Other Study ID Numbers: 314-12-401; 2013-001249-15 (EudraCT Number)