Clinical Trials Register

Summary
EudraCT Number:	2012-004825-26
Sponsor's Protocol Code Number:	G200712
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-12-04
Trial 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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2012-004825-26

A.3

Full title of the trial

Phase II, open label study of the effect of GTx-758 as secondary hormonal therapy on serum PSA and serum free testosterone levels in men with castration resistant prostate cancer maintained on androgen deprivation therapy

A GTx-758, mint másodvonalbeli hormonterápia szérum PSA és szabad tesztoszteron szintre kifejtett hatásának nyílt címkés, II. fázisú vizsgálata androgén deprivációt igénylő, kasztráció rezisztens prosztatarákos férfiakon

A.3.1

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

Clinical trial to study the effect of GTx-758 as secondary hormonal therapy on serum PSA and serum free testosterone levels who are diagnosed with castration resistant prostate cancer.

A.4.1

Sponsor's protocol code number

G200712

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	GTx, Inc.
B.1.3.4	Country	United States
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	GTx, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GTx, Inc.
B.5.2	Functional name of contact point	Michael DeSordi
B.5.3	Address:
B.5.3.1	Street Address	175 Toyota Plaza
B.5.3.2	Town/ city	Memphis
B.5.3.3	Post code	TN-38103-2674
B.5.3.4	Country	United States
B.5.4	Telephone number	1901261-3795
B.5.5	Fax number	1901844-8080
B.5.6	E-mail	mdesordi@gtxinc.com

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	GTx-758
D.3.4	Pharmaceutical form	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	Capesaris
D.3.9.1	CAS number	938067-78-8
D.3.9.2	Current sponsor code	GTx-758
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	125 to 500
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

Assessments of serum total testosterone, serum free testosterone, serum SHGB and serum PSA concentrations will be made. Bone turnover markers and the incidence and frequency of hot flashes will be assessed.
CT scan of abdomen /pelvis will be conducted to asses tumor progression and soft tissue or visceral metastases.
Bone scan will be conducted to to assess the development of new bone metastases.

E.1.1.1

Medical condition in easily understood language

blood testing to determine serum PSA level.

examine bone markers to assess the incidence and frequency of hot flashes.

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	16.1
E.1.2	Level	PT
E.1.2	Classification code	10036909
E.1.2	Term	Prostate cancer metastatic
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	16.1
E.1.2	Level	PT
E.1.2	Classification code	10062904
E.1.2	Term	Hormone-refractory prostate 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

To assess the effect of GTx-758 on serum PSA levels in men with CRPC maintained on androgen deprivation therapy (serum PSA response and serum PSA progression).

E.2.2

Secondary objectives of the trial

To assess the effect of GTx-758 on serum free testosterone levels
To assess the effect of GTx-758 on serum SHBG
To assess the effect of GTx-758 on serum total testosterone
To assess the effect of GTx-758 on adrenal gland androgen precursor hormones (DHEA and DHEAS)
To assess the effect of GTx-758 on the development of new bone metastases
To assess the effect of GTx-758 on soft tissue metastases (visceral and lymph nodes)
To assess the effects of GTx-758 on skeletal related events
To assess the effect of GTx-758 on bone turnover markers
To assess the incidence and frequency of hot flashes in men on GTx-758
To assess the safety and tolerability of GTx-758 in men with prostate cancer who have failed ADT
To assess the effect of GTx-758 on functional protein S, protein C, factor VII, factor VIII,antithrombin and tissue factor

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Be over 18 years of age.
2. Be able to communicate effectively with the study personnel
3. Have histologically confirmed prostate cancer
4. Have high risk, non-metastatic, castration resistant prostate cancer (T any – N any – M0) or have metastatic castration resistant prostate cancer (T any – N any – M1).
o Patients with non-metastatic castration resistant prostate cancer must have a PSA doubling time greater than 0 months and less than 10 months when calculated using the website below. PSA doubling time will be calculated using at least three serum PSA measurements that were obtained within 1 year prior to Day 1 of the study and that were collected over at least 3 months with a minimum of 28 days between any two successive measurements. PSA values must be greater than 0.2 ng/dL and have been obtained while the patient was maintained on ADT. The PSA doubling time will be calculated using first order kinetics and must be performed using the following website: http://nomograms.mskcc.org/Prostate/PsaDoublingTime.aspx
o Patients with metastatic castration resistant prostate cancer must have a rising serum PSA on two successive assessments at least 2 weeks apart and serum PSA levels ≥ 2 and < 250 ng/mL or > 2 and < 250 ng/mL and a 25% increase above the nadir from the ADT.
5. ECOG performance status of 0 to 2
6. Have been treated with ADT (chemical or surgical) for at least 6 months
7. Have a castrate level of serum total testosterone (<50 ng/dL)
8. Have a history of serum PSA response on ADT. A serum PSA response is an undetectable level of serum PSA (≤0.2 ng/mL) OR at least a 90% reduction in serum PSA from the serum PSA value prior to the initiation of treatment to <10 ng/mL.
9. Be continued on ADT throughout this study
10. Give written informed consent prior to any study specific procedures
11. Subjects must agree, if not already on anticoagulation therapy or aspirin, to take at least 81 mg aspirin daily throughout the duration of their participation in this study and for 30 days after completion of dosing with GTx-758.
12. Subjects must agree to use acceptable methods of contraception:
• If their female partners are pregnant or lactating, acceptable methods of contraception from the time of the first administration of study medication until 3 months following administration of the last dose of study medication must be used. Acceptable methods are: Condom used with spermicidal foam/gel/film/cream/suppository. If the subject has undergone surgical sterilization (vasectomy with documentation of azospermia), a condom with spermicidal foam/gel/film/cream/suppository should be used.
If the male subject’s partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 3 months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository [i.e., barrier method of contraception], surgical sterilization (vasectomy with documentation of azospermia) and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}, the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}.
• If the female partner has undergone documented tubal ligation (female sterilization), a barrier method {condom used with spermicidal foam/gel/film/cream/suppository} should also be used.
• If the female partner has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS), a barrier method {condom with spermicidal foam/gel/film/cream/suppository} should also be used.

E.4

Principal exclusion criteria

1. A serum PSA value ≥ 250 ng/mL.
2. Known hypersensitivity or allergy to estrogen or estrogen like drugs;
3. Need for urgent chemotherapy, radiation therapy or surgical intervention for prostate cancer in the opinion of the investigator;
4. Any disease or condition (medical or surgical) which might compromise the hematologic, cardiovascular, endocrine, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk;
5. Subjects with a personal history of abnormal blood clotting or thrombotic disease (venous or arterial thrombotic events such as history of stroke, deep vein thrombosis (DVT), and/or pulmonary embolus (PE));
6. Any subjects, as determined by a central laboratory, with:
a. a modified activated protein C reaction ratio < 2.5 and a Factor V Leiden gene mutation,
b. an antithrombin level below the lower limit of the normal range,
c. an antiphospholipid antibody level for Lupus anticoagulant or anticardiolipin that is indeterminate, positive, or outside the normal range, or
d. a prothrombin gene mutation;
7. Symptomatic congestive heart failure (NYHA Class III – IV), unstable angina pectoris, cardiac arrhythmia, or history of atrial fibrillation;
8. The presence of consistently abnormal laboratory values which are considered clinically significant. In addition, any subject with liver enzymes (ALT or AST) above 2 times the upper limit of normal, total bilirubin above 2 times the upper limit of normal, or serum creatinine above 1.5 times the upper limit of normal will NOT be admitted to the study.
9. Received an investigational drug within a period of 90 days prior to enrollment in the study;
10. Received the study medication (GTx-758) previously;
11. Currently taking testosterone, testosterone-like agents, megesterol acetate, 5α-reductase inhibitor (finasteride, dutasteride), or antiandrogens (bicalutamide, flutamide or nilutamide). Subjects taking a 5α-reductase inhibitor or one of these antiandrogens may be eligible if the subject undergoes a 6-week washout period after stopping therapy. The subject must have at least two rising serum PSA levels at least 2 weeks apart after therapy with the 5α-reductase inhibitor or these antiandrogens has been stopped (antiandrogen withdrawal) and complete the 6-week washout period to be eligible;
12. Have previously taken or are currently taking diethylstilbestrol, other estrogens, any estrogen antagonist (e.g.,tamoxifen), a selective estrogen receptor modulator (e.g., raloxifene), abiraterone, ketoconazole or any other inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase);
13. Currently having radiation therapy to prostate for cancer control (radiation to bone to relieve pain is acceptable);
14. Have previously taken or are currently taking enzalutamide;
15. Have previously received cytotoxic chemotherapy for prostate cancer;
16. Recent hospitalization (within 30 days of screening);
17. Recent surgery (within 30 days of screening);
18. Have taken body building or fertility supplements within 4 weeks of admission into the study;
19. Have been previously diagnosed or treated for active cancer (other than prostate cancer or non-melanoma skin cancer) within the previous five years;
20. Have a BMI >35.

E.5 End points

E.5.1

Primary end point(s)

The proportion of subjects with a 50% decline from baseline in serum PSA by the Day 90 visit

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 90

E.5.2

Secondary end point(s)

1. Time to serum PSA progression
2. The proportion of subjects with a ≥90% decline from baseline in serum PSA
3. The proportion of subjects with a ≥30% decline from baseline in serum PSA
4. Change in serum free testosterone levels
5. Change in serum SHBG levels
6. Change in serum total testosterone levels
7. Change in DHEA and DHEAS levels
8. Time to progression (TTP) assessed by RECIST 1.1 (soft tissue) or by PCWG2 (bone metastases)
9. Progression free Survival (PFS) assessed by RECIST 1.1 (soft tissue) or by PCWG2 (bone metastases)
10. Change in bone turnover marker levels
11. Change in incidence and frequency of hot flashes from baseline
12. Time to new or worsening SREs
13. Assess the safety and tolerability of GTx-758 in men with prostate cancer who have failed ADT
14. To assess the effect of GTx-758 on functional protein S, protein C, factor VII, factor VIII, antithrombin and tissue factor.

E.5.2.1

Timepoint(s) of evaluation of this end point

Anytime during the trial.

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

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

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

Yes

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.8.2.4

Number of treatment arms in the trial

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

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

Subjects that have not demonstrated serum PSA progression by day 360 will return every 90 days for a visit until they meet the criteria for serum PSA progression. These visits will occur within 7 days of the 90 day interval (± 7 days).

If this assessment confirms the serum PSA progression, the subject should be discontinued from the study and the End of Study visit assessments should be conducted.

After the End of Study visit the subjects have to attend at Follow-up Visits.

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2013-01-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-11-09

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