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Trial record 1 of 1 for:    NCT03072238
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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)

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ClinicalTrials.gov Identifier: NCT03072238
Recruitment Status : Active, not recruiting
First Posted : March 7, 2017
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE March 2, 2017
First Posted Date  ICMJE March 7, 2017
Last Update Posted Date September 18, 2019
Actual Study Start Date  ICMJE June 30, 2017
Estimated Primary Completion Date May 12, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 30, 2019)
Investigator-Assessed Radiographic Progression-Free Survival (rPFS) [ Time Frame: Up to approximately 31 months ]
Radiographic progression-free survival is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first. Disease progression for soft tissue is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; and an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions. Disease progression for bone lesions is defined as two or more lesions compared to baseline. rPFS will be analyzed in participants with phosphatase and tensin homolog (PTEN) - loss tumors (using the Ventana PTEN immunohistochemistry (IHC) assay) and evaluated against the intent-to-treat (ITT) population.
Original Primary Outcome Measures  ICMJE
 (submitted: March 2, 2017)
Investigator-Assessed Radiographic Progression-Free Survival (rPFS) [ Time Frame: Up to approximately 31 months ]
Radiographic progression-free survival is defined as time from date of randomization to the first occurrence of documented disease progression, as assessed by the investigator with use of the Prostate Cancer Working Group 3 (PCWG3) criteria or death from any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; and an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions. rPFS will be analyzed in participants with phosphatase and tensin homolog (PTEN)-loss tumors (using the Ventana PTEN immunohistochemistry (IHC) assay) and evaluated against the intent-to-treat (ITT) population.
Change History Complete list of historical versions of study NCT03072238 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2018)
  • Time to Pain Progression [ Time Frame: Up to approximately 7 years ]
    Pain severity progression refers to pain onset for participants who are asymptomatic at baseline or pain worsening for those who are mildly symptomatic at baseline. Pain severity will be graded on a 10-point scale, with 0=no pain and 10=severe pain. Pain severity progression is defined as a ≥ 2-point absolute increase from baseline.
  • Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: Up to approximately 7 years ]
    Time to initiation of cytotoxic chemotherapy is defined as the time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy (use of antineoplastic agents: docetaxel, cabazitaxel, mitoxantrone, estramustine, cisplatin, carboplatin, cyclophosphamide, doxorubicin, mitomycin, irinotecan, 5-fluorouracil, gemcitabine, or etoposide) for prostate cancer.
  • Overall Survival [ Time Frame: Up to approximately 7 years ]
    Overall Survival (OS) will be measured from randomization to the time of death due to any cause.
  • Time to Function Deterioration [ Time Frame: Up to approximately 7 years ]
    Time to function deterioration is defined as the time interval from the date of randomization to the date of a decrease of 10-point or more on either the 0−100 physical function (PF) or the role functioning (RF) scores from the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).
  • Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: Up to approximately 7 years ]
    Time to PSA progression is defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression is defined as ≥ 25% relative increase of ≥ 2 ng/mL above the baseline or the smallest sum on study, which is confirmed by a second consecutive value ≥ 3 weeks later.
  • Time to First Opioid Use [ Time Frame: Up to approximately 7 years ]
    Time to first opioid use is defined as the time interval from the date of randomization to the date of an initiation of opioid analgesic use for cancer-related pain, and consumption reported on at least 7 consecutive days.
  • Time to Symptomatic Skeletal Event (SSE) [ Time Frame: Up to approximately 7 years ]
    Time to first SSE is defined as the time interval from the date of randomization to the date of an SSE.
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 7 years ]
    An objective response is defined per response evaluation criteria in solid tumors (RECIST) v1.1 and PCWG3 criteria. Participants without a post-baseline tumor assessment will be considered non-responders. ORR is defined as complete response (CR) or partial response (PR). Complete response (CR) is defined as disappearance of all target lesions. Partial response (PR) is defined as least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
  • PSA Response Rate [ Time Frame: Up to approximately 7 years ]
    PSA response rate is defined as the percentage of participants achieving a PSA decline ≥50% from baseline. Participants without a post-baseline PSA assessment will be considered non-responders.
  • Investigator-Assessed rPFS in Participants With PTEN-Loss Tumors by Next-Generation Sequencing (NGS) [ Time Frame: Up to approximately 7 years ]
    Investigator-assessed rPFS (time from date of randomization to the first occurrence of documented disease progression) per PCWG3 criteria will be analyzed in participants with PTEN-loss tumors by NGS. Disease progression for soft tissue is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; and an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions. Disease progression for bone lesions is defined as two or more lesions compared to baseline.
  • Plasma concentration of ipatasertib [ Time Frame: 1-3 hours post-dose in Cycle 1, Day 1 and Day 15, Cycle 3 Day 1 and Cycle 6 Day 1 ]
    Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
  • Plasma concentration of abiraterone [ Time Frame: 1-3 hours post-dose in Cycle 1, Day 1 and Day 15, Cycle 3 Day 1 and Cycle 6 Day 1 ]
    Plasma samples for pharmacokinetic characterization was collected at various timepoints in all participants.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2017)
  • Time to Pain Progression [ Time Frame: Up to approximately 65 months ]
    Pain severity progression refers to pain onset for participants who are asymptomatic at baseline or pain worsening for those who are mildly symptomatic at baseline. Pain severity will be graded on a 10-point scale, with 0=no pain and 10=severe pain. Pain severity progression is defined as a ≥ 2-point absolute increase from baseline.
  • Time to Initiation of Cytotoxic Chemotherapy [ Time Frame: Up to approximately 65 months ]
    Time to initiation of cytotoxic chemotherapy is defined as the time interval from the date of randomization to the date of initiation of cytotoxic chemotherapy (use of antineoplastic agents: docetaxel, cabazitaxel, mitoxantrone, estramustine, cisplatin, carboplatin, cyclophosphamide, doxorubicin, mitomycin, irinotecan, 5-fluorouracil, gemcitabine, or etoposide) for prostate cancer.
  • Overall Survival [ Time Frame: Up to approximately 65 months ]
    Overall Survival (OS) will be measured from randomization to the time of death due to any cause.
  • Time to Function Deterioration [ Time Frame: Up to approximately 65 months ]
    Time to function deterioration is defined as the time interval from the date of randomization to the date of a decrease of 10-point or more on either the 0−100 physical function (PF) or the role functioning (RF) scores from the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).
  • Time to Prostate-Specific Antigen (PSA) Progression [ Time Frame: Up to approximately 65 months ]
    Time to PSA progression is defined as the time from the date of randomization to the first occurrence of PSA progression, per the PCWG3 criteria. PSA progression is defined as ≥ 25% relative increase of ≥ 2 ng/mL above the baseline or the smallest sum on study, which is confirmed by a second consecutive value ≥ 3 weeks later.
  • Time to First Opioid Use [ Time Frame: Up to approximately 65 months ]
    Time to first opioid use is defined as the time interval from the date of randomization to the date of an initiation of opioid analgesic use for cancer-related pain, and consumption reported on at least 7 consecutive days.
  • Time to Symptomatic Skeletal Event (SSE) [ Time Frame: Up to approximately 65 months ]
    Time to first SSE is defined as the time interval from the date of randomization to the date of an SSE.
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 65 months ]
    An objective response is defined per response evaluation criteria in solid tumors (RECIST) v1.1 and PCWG3 criteria. Participants without a post-baseline tumor assessment will be considered non-responders. ORR is defined as complete response (CR) or partial response (PR). Complete response (CR) is defined as disappearance of all target lesions. Partial response (PR) is defined as least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
  • PSA Response Rate [ Time Frame: Up to approximately 65 months ]
    PSA response rate is defined as the percentage of participants achieving a PSA decline ≥50% from baseline. Participants without a post-baseline PSA assessment will be considered non-responders.
  • Investigator-Assessed rPFS in Participants With PTEN-Loss Tumors by Next-Generation Sequencing (NGS) [ Time Frame: Up to approximately 65 months ]
    Investigator-assessed rPFS (time from date of randomization to the first occurrence of documented disease progression) per PCWG3 criteria will be analyzed in participants with PTEN-loss tumors by NGS. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; and an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ipatasertib Plus Abiraterone Plus Prednisone/Prednisolone, Relative to Placebo Plus Abiraterone Plus Prednisone/Prednisolone in Adult Male Patients With Metastatic Castrate-Resistant Prostate Cancer
Official Title  ICMJE 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
Brief Summary The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of ipatasertib plus abiraterone and prednisone/prednisolone compared with placebo plus abiraterone and prednisone/prednisolone in participants with metastatic castrate-resistant prostate cancer (mCRPC).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Prostate Cancer
Intervention  ICMJE
  • Drug: Ipatasertib
    Oral tablets, 400 mg, given once daily (QD) beginning on Day 1 of Cycle 1 until disease progression or intolerable toxicity
  • Drug: Abiraterone
    Oral tablets of abiraterone, 1000 mg QD, taken on an empty stomach and swallowed whole with water, plus prednisone/prednisolone, 5 mg twice daily (BID) until disease progression or intolerable toxicity
  • Drug: Placebo
    Oral tablets (matched to ipatasertib appearance), given QD beginning on Day 1 of Cycle 1 until disease progression or intolerable toxicity
Study Arms  ICMJE
  • Experimental: Ipatasertib + Abiraterone
    Ipatasertib and abiraterone, administered orally, in 28-day cycles
    Interventions:
    • Drug: Ipatasertib
    • Drug: Abiraterone
  • Active Comparator: Placebo + Abiraterone
    Placebo plus abiraterone, administered orally, in 28-day cycles
    Interventions:
    • Drug: Abiraterone
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 17, 2019)
1101
Original Estimated Enrollment  ICMJE
 (submitted: March 2, 2017)
850
Estimated Study Completion Date  ICMJE October 11, 2023
Estimated Primary Completion Date May 12, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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-α 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 reductase inhibitors within 4 weeks of Cycle 1, Day 1
  • Prior treatment with systemic radiopharmaceuticals (e.g., radium-223 and strontium-89). Radiopharmaceuticals for the purpose of imaging are permitted. Focal palliative radiation to treat cancer-related pain is permitted provided that the last treatment with radiation is at least 14 days prior to Cycle 1, Day 1.
  • Prior treatment with approved or experimental therapeutic agents with known inhibition of the PI3K pathway, including PI3K inhibitors, AKT inhibitors, and mTOR inhibitors
  • Administration of an investigational therapeutic agent within 28 days of Cycle 1, Day 1
  • Known untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsant medications or corticosteroids for symptomatic control); a CT or MRI scan of the brain will be performed at screening if required by the local health authority
  • Any chronic therapy or use of food supplements that are strong CYP3A4/5 inducers or inhibitors or sensitive substrates of CYP3A or CYP2D6 with a narrow therapeutic window

Abiraterone-Specific Exclusion Criteria:

  • Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg)
  • History of pituitary or adrenal dysfunction
  • Any ongoing cardiac arrhythmias (including atrial fibrillation) that require medical therapy

Ipatasertib-Specific Exclusion Criteria:

  • Type 1 or Type 2 diabetes mellitus requiring insulin at study entry
  • History of inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis), active bowel inflammation (e.g., diverticulitis)
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Brazil,   Canada,   China,   Costa Rica,   Denmark,   France,   Greece,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Norway,   Poland,   Portugal,   Russian Federation,   Spain,   Taiwan,   Thailand,   United Kingdom,   United States
Removed Location Countries Germany,   Slovenia
 
Administrative Information
NCT Number  ICMJE NCT03072238
Other Study ID Numbers  ICMJE CO39303
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP