Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 22 April 2024
• Main ID: NCT03072238
• Date of registration: 02/03/2017
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer IPATential150
• 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: June 30, 2017
• Target sample size: 1101
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03072238
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

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, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- Eastern Collaborative Oncology Group (ECOG) performance status of 0 or 1 at screening

- Adequate hematologic and organ function within 28 days before the first study
treatment

- Ability to comply with the study protocol, in the investigator's judgment

- Willingness and ability of participants to use the electronic device to report
selected study outcomes; Caregivers and site staff can assist with patient diary input
but patient must be able to independently comprehend and answer the questionnaires

- 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

- 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 (FFPE) tissue block (preferred)
or a minimum of 15 (20 preferred) freshly cut unstained tumor slides from the most
recently collected, available tumor tissue accompanied by an associated pathology
report (with tumor content information, Gleason score, and disease staging) for PTEN
IHC and NGS testing and for other protocol-mandated secondary and exploratory
assessments. If only 12-14 slides are available, the patient may still be eligible for
the study, after discussion with and approval by the Medical Monitor. Cytologic or
fine-needle aspiration samples are not acceptable. Tumor tissue from bone metastases
is not acceptable

- A valid PTEN IHC result (testingcentral laboratory tested with results directly sent
to IxRS) (e.g., participants with an "invalid" or "failed" PTEN IHC result are not
permitted to enroll)

- Metastatic disease documented prior to randomization by clear evidence of bone lesions
on bone scan and/or measurable soft tissue disease by computed tomography (CT) and/or
magnetic resonance imaging (MRI) (at least one target lesion) according to RECIST v1.1

- Asymptomatic or mildly symptomatic form of prostate cancer

- Progressive disease before initiating study treatment

- Ongoing androgen deprivation with gonadotropin-releasing hormone (GnRH) analog or
bilateral orchiectomy, with serum testosterone <= 50 ng/dL (<= 1.7 nmol/L) within 28
days before randomization

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)

- Need of more than 10 mg/day of prednisone or an equivalent dose of other
anti-inflammatory corticosteroids as a current systemic corticosteroid therapy to
treat a chronic disease (e.g., rheumatic disorder)

- Active infection requiring intravenous (IV) antibiotics within 14 days before Day 1,
Cycle 1

- Immunocompromised status because of current known active infection with HIV or because
of the use of immunosuppressive therapies for other conditions

- Major surgical procedure or significant traumatic injury within 28 days prior to Day
1, Cycle 1, or anticipation of the need for major surgery during study treatment

- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such
as structural heart disease (e.g., severe left ventricular systolic dysfunction, left
ventricular hypertrophy), untreated coronary heart disease (symptomatic or with
ischemia demonstrated by diagnostic testing), myocardial infarction or atrial
thrombotic events within the past 6 months, severe unstable angina, New York Heart
Association Class III and IV heart disease or depressed left ventricular ejection
fraction (LVEF; previously documented LVEF < 50% without documentation of recovery),
clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia,
hypocalcemia), or family history of sudden unexplained death or long QT syndrome

- 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
(Tis, Ta, and low grade T1 tumors), 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, 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 participants 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 (e.g., docetaxel) or biological therapy (e.g.,
vaccine, immunotherapy) 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.

- Use of opioid medications for cancer-related pain, including codeine and
dextropropoxyphene, currently or any time within 4 weeks of Day 1, Cycle 1

- Prior treatment with abiraterone or other known potent CYP17 inhibitors (e.g.,
ketoconazole, orteronel) or investigational agents that block androgen synthesis.
Previous treatment with itraconazole and fluconazole is permitted.

- Prior treatment with enzalutamide or other potent androgen-receptor blockers, approved
or experimental (e.g., ARN-509, ODM-201, or galeterone)

- Prior treatment with flutamide (Eulexin®), steroidal anti-androgens (e.g., cyproterone
acetate, chlormadinone acetate), androgens, or estrogens treatment within 4 weeks of
Cycle 1, Day 1

- Prior treatment with bicalutamide (Casodex®) or nilutamide (Nilandron®) within 6 weeks
of Cycle 1, Day 1

- Prior treatment with 5-alpha redu


Age minimum: 18 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Metastatic Prostate Cancer

Intervention(s)

Drug: Placebo

Drug: Abiraterone

Drug: Ipatasertib

Drug: Prednisone/Prednisolone

Primary Outcome(s)

Investigator-Assessed Radiographic Progression-Free Survival (rPFS) Per PCWG3 Criteria (PTEN Loss Population) [Time Frame: Up to approximately 31 months]

Investigator-Assessed Radiographic Progression-Free Survival (rPFS) Per PCWG3 Criteria (Intent-To-Treat (ITT) Population) [Time Frame: Up to approximately 31 months]

Secondary Outcome(s)

Overall Survival (OS) [Time Frame: Up to approximately 7 years]

Percentage of Participants With Adverse Events (AEs) [Time Frame: Baseline up until 28 days after the last dose of study drug or initiation of subsequent lines of anti-cancer therapy, whichever occurs first (up to a maximum of 7 years).]

Time to First Opioid Use [Time Frame: Up to approximately 7 years]

PSA Response Rate [Time Frame: Up to approximately 7 years]

Time to Initiation of Cytotoxic Chemotherapy [Time Frame: Up to approximately 7 years]

Duration of Response (DOR) [Time Frame: Up to approximately 7 years]

Plasma Concentrations of Abiraterone at Specified Timepoints [Time Frame: Pre-dose at steady state in Cycle 1, Day 15 and Cycle 3 Day 1 (each cycle length= 28 days)]

Plasma Concentrations of Ipatasertib at Specified Timepoints [Time Frame: 1-3 hours post-dose (Cycle 1, Day 1; Cycle 1 Day 15 and Cycle 3 Day 1) and pre-dose at steady state (Cycle 1 Day 15, Cycle 3 Day 1, Cycle 6 Day 1) (each cycle length= 28 days)]

Investigator-Assessed rPFS Per PCWG3 Criteria in Participants With PTEN-Loss Tumors by Next-Generation Sequencing (NGS) [Time Frame: Up to approximately 7 years]

Objective Response Rate (ORR) [Time Frame: Up to approximately 7 years]

Time to Pain Progression [Time Frame: Up to approximately 7 years]

Time to Function Deterioration [Time Frame: Up to approximately 7 years]

Time to Prostate-Specific Antigen (PSA) Progression [Time Frame: Up to approximately 7 years]

Time to Symptomatic Skeletal Event (SSE) [Time Frame: Up to approximately 7 years]

Secondary ID(s)

2016-004429-17

CO39303

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 10/04/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03072238