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Study of ORIC-101 in Combination With Enzalutamide

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ClinicalTrials.gov Identifier: NCT04033328
Recruitment Status : Recruiting
First Posted : July 26, 2019
Last Update Posted : July 15, 2021
Sponsor:
Information provided by (Responsible Party):
Oric Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE July 24, 2019
First Posted Date  ICMJE July 26, 2019
Last Update Posted Date July 15, 2021
Actual Study Start Date  ICMJE October 28, 2019
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2019)
  • Recommended Phase 2 Dose (RP2D) [ Time Frame: 12 months ]
    RP2D as determined by 3+3 dose escalation design
  • PSA Response Rate [ Time Frame: 36 months ]
    ≥50% decline from baseline at 8 weeks per Prostate Cancer Working Group 3 (PCWG3) criteria
  • PSA Progression [ Time Frame: 36 months ]
    From study start until PCWG3 criteria is met
  • Number of Participants with Adverse Events [ Time Frame: 36 months ]
    Safety and tolerability of ORIC-101 in combination with enzalutamide
  • Number of Participants with Abnormal Laboratory Values [ Time Frame: 36 months ]
    Safety and tolerability of ORIC-101 in combination with enzalutamide
  • Number of Participants with Abnormal 12-lead ECG [ Time Frame: 36 months ]
    Safety and tolerability of ORIC-101 in combination with enzalutamide
  • Number of Participants with Abnormal Vital Signs [ Time Frame: 36 months ]
    Safety and tolerability of ORIC-101 in combination with enzalutamide
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 5, 2020)
  • Maximum plasma concentration (Cmax) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide
  • Minimum plasma concentration (Cmin) [ Time Frame: 36 months ]
    PK of ORIC-101 in combination with enzalutamide
  • Time of maximum observed concentration (Tmax) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide
  • Area under the curve (AUC(0-24)) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide
  • Elimination half-life (T1/2) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide
  • Circulating tumor cells (CTCs) conversion [ Time Frame: 36 months ]
    ≥5 cells/7.5 mL of blood to 0 (zero) (CTC0), as well as from unfavorable (≥5 cells/7.5 mL of blood) to favorable (<5 cells/7.5 mL of blood)
  • Objective response rate (ORR) [ Time Frame: 36 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and PCWG3 criteria
  • Duration of response (DOR) [ Time Frame: 36 months ]
    Radiographic progression using RECIST v1.1
  • Progression-free survival (PFS) [ Time Frame: 36 months ]
    Time from first dose to first documentation of radiographic progression or death
  • Overall survival (OS) [ Time Frame: 36 months ]
    Time from first dose to death
  • Number of Participants with GR Expression by IHC [ Time Frame: 36 months ]
    Level of GR expression by IHC in tumor tissue samples
Original Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2019)
  • Maximum plasma concentration (Cmax) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide
  • Time of maximum observed concentration (Tmax) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide
  • Area under the curve (AUC(0-24)) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide
  • Elimination half-life (T1/2) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide
  • Circulating tumor cells (CTCs) conversion [ Time Frame: 36 months ]
    ≥5 cells/7.5 mL of blood to 0 (zero) (CTC0), as well as from unfavorable (≥5 cells/7.5 mL of blood) to favorable (<5 cells/7.5 mL of blood)
  • Objective response rate (ORR) [ Time Frame: 36 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and PCWG3 criteria
  • Duration of response (DOR) [ Time Frame: 36 months ]
    Radiographic progression using RECIST v1.1
  • Progression-free survival (PFS) [ Time Frame: 36 months ]
    Time from first dose to first documentation of radiographic progression or death
  • Overall survival (OS) [ Time Frame: 36 months ]
    Time from first dose to death
  • Number of Participants with GR Expression by IHC [ Time Frame: 36 months ]
    Level of GR expression by IHC in tumor tissue samples
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of ORIC-101 in Combination With Enzalutamide
Official Title  ICMJE An Open-Label Phase 1b Study of ORIC-101 in Combination With Enzalutamide in Patients With Metastatic Prostate Cancer Progressing on Enzalutamide
Brief Summary The purpose of this study is to establish the recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of ORIC-101 in combination with enzalutamide (Xtandi®) when administered to patients with metastatic prostate cancer progressing on enzalutamide.
Detailed Description

ORIC-101 is a small molecule GR antagonist being developed for the treatment of patients with solid tumor malignancies. Mechanistically, ORIC-101 inhibits GR transcriptional activity and blocks the pro-survival signals mediated by the activated nuclear receptor.

This is an open-label, single arm, multicenter, dose escalation followed by dose expansion study to assess the safety and preliminary antitumor activity of ORIC-101 in combination with enzalutamide in patients progressing on enzalutamide. Patients deemed eligible will receive treatment with ORIC-101 in addition to continuing their current enzalutamide therapy.

Escalating dose levels of ORIC-101 will be administered orally, once daily in combination with enzalutamide 160 mg. Parallel enrollment for assessment of PK/PD modulation in up to 3 additional patients presenting with tumors expressing high levels of GR (GR-high) may be performed at each dose level after the dose level has cleared the initial dose-limiting toxicity evaluation period; these additional patients may serve as supplemental patients for selection of the maximum tolerated dose and/or RP2D.

Dose expansion will further evaluate the safety and preliminary antitumor activity of ORIC-101 in patients presenting with different levels of GR expressing-tumors.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Modified interval 3+3 dose escalation design, followed by dose expansion
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostatic Neoplasms
Intervention  ICMJE
  • Drug: ORIC-101
    ORIC-101 once daily in each 28-day cycle
  • Drug: enzalutamide 40 MG oral capsule [Xtandi]
    160 mg once daily in each 28-day cycle
Study Arms  ICMJE
  • Experimental: Dose Escalation
    ORIC-101 dosed orally, once per day in combination with enzalutamide (160 mg) of each 28-day cycle.
    Interventions:
    • Drug: ORIC-101
    • Drug: enzalutamide 40 MG oral capsule [Xtandi]
  • Experimental: Dose Expansion
    RP2D dose
    Interventions:
    • Drug: ORIC-101
    • Drug: enzalutamide 40 MG oral capsule [Xtandi]
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 24, 2019)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate
  • Metastatic prostate cancer currently being treated with enzalutamide (Xtandi®) 160 mg once daily plus surgical or ongoing chemical castration, with baseline testosterone level <50 ng/dL
  • Must have been on treatment with enzalutamide for at least 3 months prior to documented evidence of PSA progression defined as per PCWG3: minimum of 2 rising values (3 measurements) obtained a minimum of one week apart with the latest result being at least 2.0 ng/mL (or 1.0 ng/mL if PSA rise is the only indication of progression)
  • Agreement and ability to undergo on-study core biopsies, as follows, through a procedure that is deemed to be clinically feasible and not carry significant risk:

    • one pre-treatment tumor biopsy obtained while on treatment with enzalutamide prior to enrollment on this study; and
    • one post-treatment tumor biopsy during Cycle 2
    • one end of treatment tumor biopsy (optional)
  • ECOG performance status 0 or 1
  • Life expectancy of at least 3 months
  • Adequate organ function as defined by the following criteria:

    • ANC ≥1500 cells/mm3 (1.5 × 103 cells/mm3)
    • Platelets ≥100,000 /µL (100 × 109 /L)
    • Hemoglobin ≥9.0 g/dL (90 g/L)
    • AST (SGOT) or ALT (SGPT) ≤2.5 × ULN, ≤5.0 × ULN for patients with liver metastases
    • Bilirubin ≤1.5 × ULN; patients with a known history of Gilbert's syndrome and/or isolated elevations of indirect bilirubin are eligible
    • QTcF ≤480 msec
  • Capable of giving signed informed consent

Exclusion Criteria:

  • No intervening therapy between enzalutamide treatment and enrollment on this study
  • Any other active malignancy, with the exception of adequately treated non-melanoma skin cancer, adequately treated superficial bladder cancer, stage 1 or 2 solid tumor malignancies without evidence of disease, or other solid tumors curatively treated with no evidence of disease for ≥5 years from enrollment
  • Current treatment on another therapeutic clinical trial
  • Prior or current treatment with ORIC-101 or any other GR antagonist (eg, CORT-125281, mifepristone, relacorilant)
  • Prior chemotherapy in the metastatic castration-resistant prostate cancer setting
  • Prior treatment with a second-generation AR modulator (eg, apalutamide, abiraterone, darolutamide)
  • History of Cushing's syndrome or adrenal insufficiency
  • History or presence of CNS metastases
  • History of seizures or condition that may predispose to seizures
  • Current (at C1D1) or requirement for chronic use of systemic corticosteroids with the exception of inhaled, topical, intraocular, intranasal, or intraarticular corticosteroids
  • Current (within 10 days prior to first dose of ORIC-101) or expected on-study treatment with specified strong CYP3A4 inhibitors or inducers
  • Receiving any other anticancer therapy, including radiotherapy within 21 days prior to C1D1. Patients must have recovered from all toxicities from prior anticancer therapies and/or radiotherapy
  • Major surgery within 21 days prior to C1D1 or incomplete recovery from adverse effects resulting from such procedure
  • Known human immunodeficiency virus (HIV) infection, unless patient is healthy and has a low risk of AIDS-related outcomes
  • Active Hepatitis B or C infection
  • Any other condition or circumstance (eg, clinical, psychological, familial, sociological, inability to swallow oral study drug) that, in the opinion of the investigator, may interfere with protocol compliance or contraindicates participation in the study
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: Rupal Patel, MS 650-388-5600 rupal.patel@oricpharma.com
Contact: Edna Chow Maneval, PhD 650-388-5600 edna.chowmaneval@oricpharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04033328
Other Study ID Numbers  ICMJE ORIC-101-02
Has Data Monitoring Committee No
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 Oric Pharmaceuticals
Study Sponsor  ICMJE Oric Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pratik S. Multani, MD Oric Pharmaceuticals
PRS Account Oric Pharmaceuticals
Verification Date July 2021

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