Condition category
Cancer
Date applied
08/10/2020
Date assigned
06/11/2020
Last edited
19/11/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
This is a study to assess the safety, tolerability, and the drug-drug interaction of the combined administration of two drugs (ipatasertib and darolutamide) in patients with prostate cancer. The primary purpose of this study is:
1: To evaluate the effect of darolutamide on the pharmacokinetics of ipatasertib and its primary metabolite M1 (G-037720)
2: To evaluate the effect of ipatasertib on the pharmacokinetics of darolutamide and its primary metabolite keto-darolutamide
(Pharmacokinetics investigates the uptake, distribution, turnover, and excretion of a drug. In this case, the investigation is aimed to see whether the pharmacokinetics of either ipatasertib or darolutamide is affected by the administration of the two drugs at the same time, which might result in an increase or a decrease of the ipatasertib/darolutamide concentrations in the body.)

Who can participate?
Males with castration-resistant prostate cancer will participate in this study

What does the study involve?
The study will comprise a screening period before the drug is taken and several treatment cycles thereafter. The screening period is 28 days prior to first administration of the study drug, and each cycle has 28 days. The total duration of the study depends on how many cycles the subject actually participates.

What are the possible benefits and risks of participating?
There is no guarantee that the patient will benefit from taking part in this clinical research study. It is possible if the patients are taking the study drugs that it may delay the growth of your cancer or extend your life. However, they may receive no medical benefit, and the study drugs may produce side effects and be harmful to the patient. The patient’s cancer may not get better, or may even get worse while they are participating in this study. During the study some side effects (unwanted effects or health problems) from the study drug or from the study procedures may be experienced. These side effects could vary from person to person.
The knowledge learned from this study may be helpful to other people with cancer in the future.

Where is the study run from?
1. Arensia Exploratory Medicine (Georgia)
2. Arensia Exploratory Medicine (Moldova)
3. Arensia Exploratory Medicine (Ukraine)

When is the study starting and how long is it expected to run for?
July 2020 to June 2024

Who is funding the study?
F. Hoffmann-La Roche Ltd. (Switzerland)

Who is the main contact?
global-roche-genentech-trials@gene.com

Trial website

Contact information

Type

Scientific

Primary contact

Dr Clinical Trials

ORCID ID

Contact details

1 DNA Way
San Francisco
94080
United States of America
+1 888-662-6728
global-roche-genentech-trials@gene.com

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

GP42658

Study information

Scientific title

An open-label, multicenter, 2-arm, phase Ib study to evaluate the pharmacokinetic drug- drug interaction between darolutamide and ipatasertib and the safety of the combination in castration-resistant prostate cancer

Acronym

Study hypothesis

To assess the safety, tolerability, and the drug-drug interaction (DDI) of the combined administration of oral ipatasertib and oral darolutamide in CRPC patients

Ethics approval

1. Approved 18/09/2020, Independent Local Ethics Committee (13a Tevdore Mgvdeli str, 3rd floor, 0112 Tbilisi, Georgia; +995 322342127; giasvan@gmail.com), ref: none provided
2. Approved 23/10/2020, Ethics Committee at Medical Center of Limited Liability Company “Harmoniya Krazy” (01135, Ukraine, Kyiv, Chornovola str., 12; +38 0442279432; no email provided), ref: none provided

Study design

Open-label multicenter 2-arm Phase Ib study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

No participant information sheet available

Condition

Prostate cancer

Intervention

This is a non-randomized, open-label, single sequence, crossover study. All subjects will receive both study drugs. There are 2 study arms (with approximately 15 subjects each) that will be executed sequentially. Whether Arm 2 will be executed will be determined after review of interim PK and safety data derived from patients in Arm 1. In addition, the dose of ipatasertib to be used in Arm 2 (i.e., 400 mg or 500 mg) will be selected based on this interim analysis.

Patients in Arm 1 will receive the following treatments:
Cycle 1:
● Period 1: ipatasertib monotherapy (400 mg QD) from Day 1 to Day 10
● Period 2: ipatasertib (400 mg QD) + darolutamide (600 mg twice daily [BID]) combination
from Day 11 to Day 28
Cycle 2 and beyond:
● Ipatasertib (400 mg QD) + darolutamide (600 mg BID) combination from Day 1 to Day 28 in each cycle

Patients in Arm 2 will receive the following treatments:
Cycle 1:
● Period 1: darolutamide monotherapy (600 mg BID) from Day 1 to Day 10
● Period 2: darolutamide (600 mg BID) + ipatasertib (400 mg or 500 mg QD) combination
from Day 11 to Day 28
Cycle 2 and beyond:
● Darolutamide (600 mg BID) + ipatasertib (400 mg or 500 mg QD) combination from Day 1 to Day 28 in each cycle
Whether Arm 2 will be executed will be determined after review of interim PK and safety data derived from patients in Arm 1. In addition, the dose of ipatasertib to be used in Arm 2 ( i.e., 400 mg or 500 mg) will be selected based on this interim analysis.

The study treatment will be given to the patients beyond Cycle 2 (each cycle will last 28 days) until disease progression, intolerable toxicity, withdrawal of consent, the decision of the Investigator, or study termination.

Intervention type

Drug

Phase

Phase I

Drug names

Darolutamide, ipatasertib

Primary outcome measure

The safety, tolerability, and the DDI of study drugs assessed through pharmacokinetic analysis measured using:
Arm 1: Plasma samples will be collected on Day 10 and Day 28 of Cycle 1, where ipatasertib and M1 (G-037720) levels will be measured on Day 10 and Day 28 of Cycle 1 and darolutamide and keto-darolutamide will be measured only on Day 28 of Cycle 1
Arm 2: Plasma samples will be collected on Day 10 and Day 28 of Cycle 1, where darolutamide and keto-darolutamide levels will be measured on Day 10 and Day 28 of Cycle1 and ipatasertib and M1 (G-037720) will be measured only on Day 28 of Cycle 1

Secondary outcome measures

There are no secondary outcome measures

Overall trial start date

10/07/2020

Overall trial end date

01/06/2024

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

General Inclusion Criteria:
1. Age ≥18 years
2. Eastern Collaborative Oncology Group performance status of 0 or 1 at screening
3. Adequate hematologic and organ function
4. Ability to comply with the study protocol, per Investigator judgment
5. Life expectancy of at least 6 months
6. Agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Disease-Specific Inclusion Criteria:
7. Histologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or small-cell features and has progressed during treatment of at least one hormonal therapy
8.Asymptomatic or mildly symptomatic form of prostate cancer
9. Progressive disease before initiating study treatment

Participant type

Patient

Age group

Mixed

Gender

Male

Target number of participants

Approximately 30 patients (15 patients each arm)

Participant exclusion criteria

General Exclusion Criteria:
1. History of malabsorption syndrome or other condition that would interfere with enteral absorption or other impairment of gastrointestinal (GI) function
2. Liver cirrhosis, current alcohol abuse, or current known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), or other clinically significant history of liver disease
3. Need of more than 10 mg/day of prednisone or an equivalent dose of other corticosteroids as a current systemic corticosteroid therapy to treat a chronic disease
4. History of another malignancy within 5 years prior, unless the patient has undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to have a recurrence rate of < 5% at 5 years
5. Any other diseases; cardiovascular, pulmonary, or metabolic dysfunction; physical examination finding; or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patients at high risk from treatment complications

Disease-Specific Exclusion Criteria:
6. Pathologic findings consistent with small-cell or neuroendocrine carcinoma of the prostate
7. Any therapy including chemotherapy or biological therapy for the treatment of CRPC In the case of hormone-sensitive prostate cancer, chemotherapy is permitted provided that it is initiated within 6 months from the time of first castration
8. Known untreated or active central nervous system (CNS) metastases
9. Use of any medications (only for the first 12 days of Arm 1) that may have the potential to affect heart rate or QTc Interval

Darolutamide-Specific Exclusion Criteria:
10. Uncontrolled hypertension, recent stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure New York Heart Association (NYHA) Class III or IV
11. Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of darolutamide
12. Known hypersensitivity to darolutamide or any of its ingredients

Ipatasertib-Specific Exclusion Criteria:
13. Type 1 or Type 2 diabetes mellitus requiring insulin at study entry
14. History of inflammatory bowel disease
15. Any ongoing cardiac arrhythmias (including uncontrolled atrial fibrillation) that require medical therapy
16. Uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
17. Lung disease

Recruitment start date

17/11/2020

Recruitment end date

23/03/2021

Locations

Countries of recruitment

Georgia, Moldova, Ukraine

Trial participating centre

Arensia Exploratory Medicine
13a Tevdore Mgvdeli st.
Tbilisi
0112
Georgia

Trial participating centre

Arensia Exploratory Medicine
29 N. Testemitanu St
Chisinau
2025
Moldova

Trial participating centre

Arensia Exploratory Medicine
31 Blyzhnya St.
Dnipropetrovsk
43102
Ukraine

Sponsor information

Organisation

Roche (United States) (Genentech, Inc)

Sponsor details

1 DNA Way
South San Francisco
94080
United States of America
+1 888-662-6728
global-roche-genentech-trials@gene.com

Sponsor type

Industry

Website

http://www.roche.com/about_roche/roche_worldwide.htm

Funders

Funder type

Industry

Funder name

Genentech

Alternative name(s)

Genentech, Inc., Genentech Inc, Genentech USA Inc, The Genentech, Genentech Inc., Genentech USA, Inc., Genentech USA Inc.

Funding Body Type

private sector organisation

Funding Body Subtype

For-profit companies (industry)

Location

United States of America

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date.

Intention to publish date

01/10/2024

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

19/11/2020: The following changes were made to the trial record: 1. The contact was updated. 2. The plain English summary was updated to reflect these changes. 09/11/2020: Internal review. 27/10/2020: Trial’s existence confirmed by Ministry of health, labor and social protection of the Republic of Moldova