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: 5 June 2017
• Main ID: EUCTR2016-004429-17-ES
• Date of registration: 18/05/2017
• Prospective Registration: No
• Primary sponsor: Roche Farma S.A.(S.A.U.)que realiza el ensayo en España y que actúa como representante de 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: 11/05/2017
• Target sample size: 850
• 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 bone lesions on bone scan or soft tissue disease by computed tomography (CT) or magnetic resonance imaging (MRI) scan
- 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 >= 1 ng/mL measured >= 1 week apart 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 Response Evaluation Criteria in Solid Tumors, Version 1.1 (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 212
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 638

Exclusion criteria:
- Inability or unwillingness to swallow whole pills
- History of malabsorption syndrome or 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 virus (HBV) or hepatitis C virus (HCV)
Patients who are positive for anti-HBc are eligible only if test results are also positive for HbsAg and polymerase chain reaction is negative for HBV DNA
Patients who are positive for HCV serology are eligible only if testing for HCV RNA is negative
- Need for current chronic corticosteroid therapy (> 10 mg/day of prednisone or an equivalent dose of other anti inflammatory corticosteroid), except concurrent use of inhaled corticosteroids
- Active infection requiring intravenous antibiotics within 14 days before Day 1, Cycle 1
- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
- Current treatment with medications that are well known to prolong the QT interval
- History of other malignancy within the previous 5 years, except for appropriately treated non-melanoma skin carcinoma, or patients who have undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to be at low risk for recurrence
- 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
- Treatment with chemotherapy for the treatment of castration-resistant prostate cancer
- In the setting of chemotherapy received for hormone-sensitive prostate cancer, treatment with chemotherapy initiated more than 6 months after time of first castration (i.e., delayed initiation of chemotherapy for HSPC). Patients should not have progressed during or within 3 months after the completion of chemotherapy-based treatment (i.e. rapid progression on chemotherapy for HSPC).
- Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or any time within 4 weeks of Day 1, Cycle 1
- Any prior anti-cancer therapy
- Known untreated or active central nervous system (CNS) metastases
- Patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria:
An evaluable or measurable disease according to the inclusion criteria outside the CNS
Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
No history of intracranial hemorrhage or spinal cord hemorrhage
Minimum of 2 weeks between completion of radiotherapy and Day 1, Cycle 1, and recovery from significant (Grade >= 3) acute toxicity, with no ongoing requirement for >= 10 mg/day of prednisone or an equivalent dose of another corticosteroid
Abiraterone-Specific Exclusion Criteria:
- Uncontrolled hypertension
- History of pituitary or adrenal dysfunction
- Atrial fibrillation or other cardiac arrhythmia requiring therapy
- Any chr

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

Health Condition(s) or Problem(s) studied

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

Metastatic Castrate-Resistant Prostate Cancer
MedDRA version: 20.0 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 100000004864

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: 1000-

Primary Outcome(s)

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

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

Timepoint(s) of evaluation of this end point: 1. Approximately 65 months

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

Secondary Outcome(s)

Secondary end point(s): 1) Time to pain progression
2) Time to initiation of cytotoxic chemotherapy for prostate cancer
3) Overall survival
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

Timepoint(s) of evaluation of this end point: 1-11. Approximately 65 months
12-13. Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, and Cycle 6 Day 1

Secondary ID(s)

CO39303

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd