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

Phase 1

Terminated

• Conditions: Breast Cancer; Ovarian Cancer; Prostate Cancer; Salivary Gland Cancer; Endometrial Cancer; Squamous Cell Carcinoma of the Cervix
• Interventions: Drug: OPB-111001

• Registration Number: NCT02042885
• Lead Sponsor: Otsuka Novel Products GmbH

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-01-17
• Study First Submitted QC: 2014-01-20
• Study First Posted: 2014-01-23
• Status Verified: 2014-07
• Primary Completion: 2015-02
• Study Completion: 2015-02
• Last Update Submitted: 2015-10-19
• Last Update Posted: 2015-10-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 79

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
1: Regimen A Escalation	OPB-111001	1: OPB-111001, orally, once weekly
2: Regimen A Extension	OPB-111001	2: OPB-111001, orally, once weekly
3: Regimen B Escalation	OPB-111001	3: OPB-111001, orally, 2 - 3 times per week
4: Regimen B Extension	OPB-111001	4: OPB-111001, orally, 2 - 3 times per week

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose / Recommended Phase 2 dose; Tolerability	after 2 or 6 weeks depending on study part; continously

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetic parameters for OPB-111001 and its metabolites	repeatedly until end of study (average of 3 months assumed)	Frequent sampling during Cycle 1 to 3, D1 only from Cycle 4 onwards
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)

Trial Locations

Locations (2)

NIHR/Wellcome Trust Imperial CRF/Imperial College Healthcare NHS Trust, Imperial Centre for Translational and Experimental Medicine (L-Block), Hammersmith Hospital; 🇬🇧 London, United Kingdom

The Institute of Cancer Research, Royal Marsden NHS Foundation Trust; 🇬🇧 London, Sutton, Surrey, United Kingdom