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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 : February 20, 2020
Sponsor:
Information provided by (Responsible Party):
Oric Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Drug: ORIC-101 Drug: enzalutamide 40 MG oral capsule [Xtandi] Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
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
Official Title: An Open-Label Phase 1b Study of ORIC-101 in Combination With Enzalutamide in Patients With Metastatic Prostate Cancer Progressing on Enzalutamide
Actual Study Start Date : October 28, 2019
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Dose Escalation
ORIC-101 dosed orally, once per day in combination with enzalutamide (160 mg) of each 28-day cycle.
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

Experimental: Dose Expansion
RP2D dose
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




Primary Outcome Measures :
  1. Recommended Phase 2 Dose (RP2D) [ Time Frame: 12 months ]
    RP2D as determined by 3+3 dose escalation design

  2. PSA Response Rate [ Time Frame: 36 months ]
    ≥50% decline from baseline at 8 weeks per Prostate Cancer Working Group 3 (PCWG3) criteria

  3. PSA Progression [ Time Frame: 36 months ]
    From study start until PCWG3 criteria is met

  4. Number of Participants with Adverse Events [ Time Frame: 36 months ]
    Safety and tolerability of ORIC-101 in combination with enzalutamide

  5. Number of Participants with Abnormal Laboratory Values [ Time Frame: 36 months ]
    Safety and tolerability of ORIC-101 in combination with enzalutamide

  6. Number of Participants with Abnormal 12-lead ECG [ Time Frame: 36 months ]
    Safety and tolerability of ORIC-101 in combination with enzalutamide

  7. Number of Participants with Abnormal Vital Signs [ Time Frame: 36 months ]
    Safety and tolerability of ORIC-101 in combination with enzalutamide


Secondary Outcome Measures :
  1. Maximum plasma concentration (Cmax) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide

  2. Time of maximum observed concentration (Tmax) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide

  3. Area under the curve (AUC(0-24)) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide

  4. Elimination half-life (T1/2) [ Time Frame: 28 Days ]
    PK of ORIC-101 in combination with enzalutamide

  5. 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)

  6. Objective response rate (ORR) [ Time Frame: 36 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and PCWG3 criteria

  7. Duration of response (DOR) [ Time Frame: 36 months ]
    Radiographic progression using RECIST v1.1

  8. Progression-free survival (PFS) [ Time Frame: 36 months ]
    Time from first dose to first documentation of radiographic progression or death

  9. Overall survival (OS) [ Time Frame: 36 months ]
    Time from first dose to death

  10. Number of Participants with GR Expression by IHC [ Time Frame: 36 months ]
    Level of GR expression by IHC in tumor tissue samples



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 ≤450 msec, ≤480 msec for patients with bundle branch block (BBB)
  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04033328


Contacts
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Contact: Rupal Patel, MS 650-388-5600 rupal.patel@oricpharma.com
Contact: Edna Chow Maneval, PhD 650-388-5600 edna.chowmaneval@oricpharma.com

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Emelei Klein    646-422-4358      
Principal Investigator: Abida Wasim, MD         
United States, South Carolina
Carolina Urologic Research Center Recruiting
Myrtle Beach, South Carolina, United States, 29572
Contact: Katie Valipour    843-449-1010 ext 268    kvalipour@curcmb.com   
Principal Investigator: Neal Shore, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       GUClinicalTrials@mdanderson.org   
Principal Investigator: Eleni Efstathiou, MD         
Sponsors and Collaborators
Oric Pharmaceuticals
Investigators
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Study Director: Pratik S. Multani, MD Oric Pharmaceuticals

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Responsible Party: Oric Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04033328    
Other Study ID Numbers: ORIC-101-02
First Posted: July 26, 2019    Key Record Dates
Last Update Posted: February 20, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases