A Study of Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Asymptomatic or Mildly Symptomatic, Previously Untreated, Metastatic Castrate-Resistant Prostate Cancer

• Register: EUCTR
• Last refreshed on: 10 August 2021
• Main ID: EUCTR2016-004429-17-HU
• Date of registration: 11/05/2017
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Study of Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Asymptomatic or Mildly Symptomatic, Previously Untreated, Metastatic Castrate-Resistant Prostate Cancer
• Scientific title: A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER TRIAL TESTING IPATASERTIB PLUS ABIRATERONE PLUS PREDNISONE/PREDNISOLONE, RELATIVE TO PLACEBO PLUS ABIRATERONE PLUS PREDNISONE/PREDNISOLONE IN ADULT MALE PATIENTS WITH ASYMPTOMATIC OR MILDLY SYMPTOMATIC, PREVIOUSLY UNTREATED, METASTATIC CASTRATE-RESISTANT PROSTATE CANCER
• Date of first enrolment: 30/06/2017
• Target sample size: 1100
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004429-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Brazil, Canada, China, Costa Rica, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Norway, Poland, Portugal, Russian Federation, Slovenia, Spain, Sweden, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Aged >= 18 years
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Adequate hematologic and organ function test results within 28 days before the first study treatment
- Life expectancy of at least 6 months
- Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined in the protocol
- For enrollment into the China extension cohort, residence in the People's Republic of China
Disease-Specific Inclusion Criteria:
- Histologically confirmed prostate adenocarcinoma without neuroendocrine differentiation or small-cell features
- Consent to provide a formalin-fixed, paraffin-embedded tissue block or a minimum of 15 freshly cut unstained tumor slides from the most recently collected, available tumor tissue accompanied by an associated pathology report
- A valid PTEN IHC result
- Metastatic disease documented prior to randomization by clear evidence of bone lesions by bone scan and/or measurable soft tissue disease by computed tomography (CT) and/ or magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors, Version 1.1(RECIST v1.1)
- Asymptomatic or mildly symptomatic form of prostate cancer
- Progressive disease before initiating study treatment, defined using at least one of the following criteria:
. Two rising prostate-specific antigen (PSA) levels measured >= 1 week apart with second result >= 1 ng/mL according to Prostate Cancer Working Group 3 (PCWG3) criteria (Patients who have received an anti-androgen therapy must have PSA progression after withdrawal [>= 4 weeks since last flutamide or >= 6 weeks since last treatment of bicalutamide or nilutamide])
. Radiographic evidence of disease progression in soft tissue according to RECIST v1.1 and/or bone scan according to PCWG3 criteria
- Ongoing androgen deprivation with gonadotropin-releasing hormone analog or bilateral orchiectomy, with serum testosterone <= 50 ng/dL (<= 2.0 nmol/L) within 28 days before randomization
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 275
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 825

Exclusion criteria:
-Inability or unwillingness to swallow whole pills
-History of malabsorption syndrome/other condition that would interfere with enteral absorption
-Clinically significant history of liver disease consistent with Child-Pugh Class B or C including cirrhosis, current alcohol abuse or current known active infection with hepatitis B or B virus
.Patients positive for anti-HBc are eligible only if test results are negative for HBsAg and polymerase chain reaction is negative for HBV DNA
.Patients positive for HCV serology are eligible only if testing for HCV RNA is negative
-Need of more than 10 mg/day of prednisone or equivalent dose of other anti-inflammatory corticosteroids as a current systemic corticosteroid therapy to treat a chronic disease
-Active infection requiring intravenous antibiotics within 14 days before Day1 Cycle 1 (D1 C1)
-History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
-History of another malignancy within 5 years prior to randomization except for either adequately treated non-melanomatous carcinoma of the skin, adequately treated melanoma in situ, adequately treated non-muscle-invasive urothelial carcinoma of the bladder or other malignancies where 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
-Any other diseases, 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
-Pathologic findings consistent with small-cell or neuroendocrine carcinoma of the prostate
-Any therapy including chemotherapy or biological therapy for the treatment of castration-resistant prostate cancer. Previous treatment with flutamide, steroidal anti-androgens, androgens, estrogens, bicalutamide, nilutamide, or 5-a reductase inhibitor is permitted
-In the setting of chemotherapy received for hormone-sensitive prostate cancer, treatment with chemotherapy initiated more than 6 months after time of first castration (delayed initiation of chemotherapy for HSPC). Patients should not have progressed during/within 3 months after the completion of chemotherapy-based treatment (rapid progression on chemotherapy for HSPC)
-Use of opioid medication for cancer-related pain including codeine and dextropropoxyphene currently or any time within 4 weeks of D1 C1
-Prior treatment with abiraterone/other known potent CYP17 inhibitors or investigational agents that block androgen synthesis. Prior treatment with itraconazole and fluconazole is permitted
-Prior treatment with enzalutamide/other potent androgen-receptor blockers approved or experimental
-Prior treatment with flutamide, steroidal anti-androgens, androgens or estrogens treatment within 4 weeks of C1 D1
-Prior treatment with bicalutamide/nilutamide within 6 weeks of C1 D1
-Prior treatment with 5a reductase inhibitors within 4 weeks of C1 D1
-Prior treatment with systemic radiopharmaceuticals (except for imaging). Focal palliative radiation to treat cancer-related pain is permitted provided that the last treatment with radiation is at least 14 days prior to C1 D1
-Prior treatment with approved or experimental therapeutic agents with known inhibition of the PI3K pathway, including PI3K inhibito

Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Metastatic Castrate-Resistant Prostate Cancer
MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: ipatasertib 100mg
Product Code: RO5532961
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ipatasertib
Current Sponsor code: RO5532961
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: ipatasertib 200mg
Product Code: RO5532961
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ipatasertib
Current Sponsor code: RO5532961
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: Zytiga
Pharmaceutical Form: Tablet
INN or Proposed INN: Abiraterone acetate
CAS Number: 154229-18-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: Zytiga
Pharmaceutical Form: Tablet
INN or Proposed INN: Abiraterone acetate
CAS Number: 154229-18-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Zytiga
Pharmaceutical Form: Tablet
INN or Proposed INN: Abiraterone acetate
CAS Number: 154229-18-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Main Objective: • To evaluate To evaluate the efficacy in the intent to treat (ITT) population
• To evaluate the efficacy in patients with PTEN-loss tumors by immunohistochemistry (IHC)

Primary end point(s): 1) Investigator-assessed radiographic progression-free survival (rPFS), per PCWG3 criteria

Secondary Objective: • To evaluate the clinical benefit in the ITT population, and in patients with PTEN-loss tumors by IHC
• To evaluate the efficacy in patients with Phosphatase and tensin homolog (PTEN)-loss tumors by next-generation sequencing
• To evaluate the safety in the ITT population and in patients with PTEN-loss tumors by IHC
• To characterize ipatasertib and abiraterone pharmacokinetics
• To characterize ipatasertib exposure, abiraterone exposure in relation to efficacy and safety

Timepoint(s) of evaluation of this end point: 1. Approximately 7 years

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1-11. Approximately 7 years
12-13. Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, and Cycle 6 Day 1

Secondary end point(s): 1) Overall survival
2) Time to pain progression
3) Time to initiation of cytotoxic chemotherapy for prostate cancer
4) Time to function deterioration per European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 physical function and role functioning
5) Time to PSA progression, per the PCWG3 criteria
6) Time to first opioid use
7) Time to symptomatic skeletal events
8) Objective response rate, per RECIST v1.1 and PCWG3 criteria in patients with measurable disease
9) PSA response rate
10) Investigator-assessed rPFS per PCWG3 criteria
11) Incidence, nature, and severity of adverse events
12) Plasma concentration of ipatasertib and abiraterone
13) Relationship between plasma concentration or PK parameters of ipatasertib and abiraterone, via safety and efficacy endpoints

Secondary ID(s)

2016-004429-17-PT

CO39303

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 28/06/2017
Contact: