Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE1
41 participants
INTERVENTIONAL
2019-10-28
2023-12-04
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Dose Escalation
ORIC-101 dosed orally, once per day in combination with enzalutamide (160 mg) of each 28-day cycle.
ORIC-101
ORIC-101 once daily in each 28-day cycle
enzalutamide 40 MG oral capsule [Xtandi]
160 mg once daily in each 28-day cycle
Dose Expansion
RP2D dose
ORIC-101
ORIC-101 once daily in each 28-day cycle
enzalutamide 40 MG oral capsule [Xtandi]
160 mg once daily in each 28-day cycle
Interventions
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ORIC-101
ORIC-101 once daily in each 28-day cycle
enzalutamide 40 MG oral capsule [Xtandi]
160 mg once daily in each 28-day cycle
Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
MALE
No
Sponsors
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ORIC Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Pratik S. Multani, MD
Role: STUDY_DIRECTOR
ORIC Pharmaceuticals
Locations
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Memorial Sloan Kettering Cancer Center
New York, New York, United States
Carolina Urologic Research Center
Myrtle Beach, South Carolina, United States
MD Anderson Cancer Center
Houston, Texas, United States
Countries
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References
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Abida W, Hahn AW, Shore N, Agarwal N, Sieber P, Smith MR, Dorff T, Monk P, Rettig M, Patel R, Page A, Duff M, Xu R, Wang J, Barkund S, Pankov A, Wang A, Junttila MR, Multani PS, Daemen A, Chow Maneval E, Logothetis CJ, Morris MJ. Phase I Study of ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Progressing on Enzalutamide. Clin Cancer Res. 2024 Mar 15;30(6):1111-1120. doi: 10.1158/1078-0432.CCR-23-3508.
Other Identifiers
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ORIC-101-02
Identifier Type: -
Identifier Source: org_study_id