Clinical Trials Register

Summary
EudraCT Number:	2013-001249-15
Sponsor's Protocol Code Number:	314-12-401
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2013-09-24
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2013-001249-15

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A clinical trial to determine the most suitable dose of OPB-111001 in patients with advanced cancer

A.3.2

Name or abbreviated title of the trial where available

Study Evaluating Tolerability and Anti-tumour activity of OPB 111001

A.4.1

Sponsor's protocol code number

314-12-401

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Otsuka Novel Products GmbH
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Otsuka Novel Products GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Otsuka Novel Products GmbH
B.5.2	Functional name of contact point	Clinical Program Leader
B.5.3	Address:
B.5.3.1	Street Address	Erika-Mann-Str. 21
B.5.3.2	Town/ city	Munich
B.5.3.3	Post code	80636
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49 89 2060205 0
B.5.5	Fax number	+49 89 2060205 96
B.5.6	E-mail	clinicaltrial-314-12-401@otsuka.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	OPB-111001 5mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	OPB-111001
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	OPB-111001 25mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	OPB-111001
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	OPB-111001 100mg
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	OPB-111001
D.3.9.4	EV Substance Code	AS3
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

• Advanced prostate cancer
• Advanced epithelial ovarian cancer, advanced squamous cell
carcinoma of the cervix, advanced breast cancer, endometrial
cancer, and salivary gland cancer that are poorly responsive to
standard treatment options

E.1.1.1

Medical condition in easily understood language

•Advanced prostate cancer
•Advanced epithelial ovarian cancer, advanced squamous cell carcinoma
of the cervix, advanced breast cancer, advanced endometrial cancer &
advanced salivary gland cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10061934
E.1.2	Term	Salivary gland cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10060862
E.1.2	Term	Prostate cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10014733
E.1.2	Term	Endometrial cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10041848
E.1.2	Term	Squamous cell carcinoma of the cervix
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10006187
E.1.2	Term	Breast cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	PT
E.1.2	Classification code	10033128
E.1.2	Term	Ovarian cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The principal objective of this clinical study is to find out how well the patients can tolerate OPB-111001 and to find the maximum tolerated dose in patients with cancer of the prostate, ovary, cervix, endometrium, breast, or salivary gland

E.2.2

Secondary objectives of the trial

The secondary objective is to look at how the drug responds in the body when administrated to a patient and its initial effect on the type of cancer.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The patient should meet the following inclusion criteria to be considered for enrollment into the study

1. Patients ≥18 years of age at Screening

2. 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 with any of the following diseases
who have exhausted standard treatment options:

a. recurrent or refractory ovarian cancer
b. recurrent or refractory cervical squamous cell carcinoma
c. recurrent or refractory breast cancer
d. recurrent or refractory salivary gland cancer
e. recurrent or refractory endometrial cancer

3. Histologically or cytologically documented diagnosis of cancer

4. Measurable disease according to Response Evaluation Criteria in Solid Tumours
(RECIST), Version 1.1 or

a. for prostate cancer also evaluable disease (nonmeasurable) defined as
prostate-specific antigen progression according to Prostate Cancer Working
Group 2 eligibility criteria
b. for ovarian cancer also evaluable disease (nonmeasurable) according to the
Gynaecologic Cancer Intergroup

5. Absolute neutrophil count ≥1.5 (1500/mm3) and platelets ≥100 × 10E9/L (without
platelet transfusion within the last 4 weeks before first study drug
administration), and haemoglobin ≥9 g/dL at Screening

6. 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

7. Albumin ≥26 g/L at Screening

8. Estimated life expectancy >3 months (as judged by investigator)

9. Eastern Cooperative Oncology Group performance status ≤1

10. In prostate cancer patients: ongoing therapy with luteinizing hormone
releasing hormone analogue or orchiectomy

11. Agreement of female patients of childbearing potential and male patients who
have partners capable of reproduction to use an effective double-barrier
contraceptive method during the course of the study and for 3 months following
the completion of their last treatment. Females of childbearing potential must
have a negative beta-human chorionic gonadotropin pregnancy test result within
3 days of the first study drug administration. Female patients who are
surgically sterilized or who are >45 years old and have not experienced menses
for >2 years may have the beta-human chorionic gonadotropin pregnancy test
waived.

12. Ability to understand and give written informed consent and to comply with the
protocol (i.e., with all study-related procedures, medication use, and
evaluations)

E.4

Principal exclusion criteria

1. 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 IMP administration.

2. 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).

3. Treatment with systemic glucocorticosteroids of more than a 2 mg dexamethasone
equivalent (e.g., 13 mg prednisolone) per day or in cases of treatment with ≤2
mg dexamethasone equivalent per day:
a. Dosing was changed within 6 weeks before Screening
or
b. The patient’s cancer is responding to glucocorticosteroid intake(as by
investigator judgment)

4. Radiation therapy within 4 weeks prior to the first dosing with IMP.

5. Treatment with a systemic IMP in a clinical trial within 28 days before the
Screening visit.

6. Use of prohibited medications within 21 days of the first dose of IMP.

7. Current or past history of clinically significant gastrointestinal disease or
major gastrointestinal surgery, malabsorption syndrome, or other conditions that
could interfere with enteral absorption.

8. Significant uncontrolled cardiovascular disease or cardiac insufficiency (New
York Heart Association classes III to IV) or a history of ventricular arrhythmia
requiring medication.

9. Patients with symptomatic central nervous system metastasis.

10. History of positive human immunodeficiency virus test result (enzyme-linked
immunosorbent assay or Western blot)

11. Clinical or laboratory evidence of active or chronic hepatitis B or hepatitis C
infection.

12. Major surgery ≤4 weeks before the first study drug administration or ongoing
side effects of previous major surgery.

13. 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.

14. Active treatment/chemotherapy for another primary malignancy within the past 3
years (except for nonmelanoma skin cancer and cervical carcinoma in situ).

15. Women who are pregnant or breastfeeding.

16. Known or suspected hypersensitivity to the excipients (ingredients) in the
study drug formulation.

E.5 End points

E.5.1

Primary end point(s)

The primary outcome measures are the determine the safety and tolerability of OPB111001 in order to establish an MTD and recommended phase II dose. This will be achieved by monitoring the incidence of AEs (defined by NCI CTCAE V4), along with vital signs, clinical laboratory parameters and electrocardiography assessments.

E.5.1.1

Timepoint(s) of evaluation of this end point

1) MTD/RP2D - Dose Escalation Part: After 1 or 3 cycles of treatment, Tolerability:
Continuously

E.5.2

Secondary end point(s)

1) Pharmacokinetic parameters for OPB-111001 and its metabolites: Area under the
curve (AUC), maximum plasma drug concentration after single dose administration
(Cmax), time to maximum plasma drug concentration after single dose
administration (tmax)and terminal elimination half-life, t1/2 and for OPB-
111001: Systemic clearance(CL/F)
2) Assessment of antitumour activity as defined by Response Evaluation Criteria in
Solid Tumours (RECIST), Version 1.1: complete response(CR), partial response
(PR), stable disease (SD), objective response rate(ORR) (CR + PR)
3) Prostate-specific antigen (PSA) response in patients with prostate cancer:
relative change determined according to Prostate Cancer Working Group 2 (PCWG2)
4) CA125 response in patients with ovarian cancer: relative change determined
according to the Gynaecologic Cancer Intergroup (GCIG)
5) Time to Treatment Failure (TTF)

E.5.2.1

Timepoint(s) of evaluation of this end point

1), 2), 3), 4) Repeatedly until end of study; 5) At end of study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

First part of the trial is a phase 1 dose escalation study and the second part is a phase 2a study

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end-of-trial date is defined as the last date of contact for the last patient completing or withdrawing from the trial.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1