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Prostatic NeoplasmsPhase 1NCT04033328

Study of ORIC-101 in Combination With Enzalutamide

A Phase 1 study testing ORIC-101 and enzalutamide 40 MG oral capsule [Xtandi] in people with Prostatic Neoplasms, run by ORIC Pharmaceuticals at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostatic Neoplasms
What is being tested?
ORIC-101 and enzalutamide 40 MG oral capsule [Xtandi]
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
3 sitesUnited States
Study dates
28 Oct 2019to 4 Dec 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Carolina Urologic Research Center

    Myrtle Beach, South Carolina, 29572

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: An Open-Label Phase 1b Study of ORIC-101 in Combination With Enzalutamide in Patients With Metastatic Prostate Cancer Progressing on Enzalutamide

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.

Read the 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.

Being tested
ORIC-101, enzalutamide 40 MG oral capsule [Xtandi]
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ORIC-101Drug

    ORIC-101 once daily in each 28-day cycle

  • enzalutamide 40 MG oral capsule [Xtandi]Drug

    160 mg once daily in each 28-day cycle

Study groups in NCT04033328
Study groupRoleWhat they receive
Dose EscalationExperimentalORIC-101 dosed orally, once per day in combination with enzalutamide (160 mg) of each 28-day cycle.
Receives: Drug: ORIC-101; Drug: enzalutamide 40 MG oral capsule [Xtandi]
Dose ExpansionExperimentalRP2D dose
Receives: Drug: ORIC-101; Drug: enzalutamide 40 MG oral capsule [Xtandi]

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended Phase 2 Dose (RP2D)

    RP2D as determined by 3+3 dose escalation design

    Measured: 12 months

  2. PSA Response Rate

    ≥50% decline from baseline at 8 weeks per Prostate Cancer Working Group 3 (PCWG3) criteria

    Measured: 36 months

  3. PSA Progression

    From study start until PCWG3 criteria is met

    Measured: 36 months

  4. Number of Participants with Adverse Events

    Safety and tolerability of ORIC-101 in combination with enzalutamide

    Measured: 36 months

  5. Number of Participants with Abnormal Laboratory Values

    Safety and tolerability of ORIC-101 in combination with enzalutamide

    Measured: 36 months

  6. Number of Participants with Abnormal 12-lead ECG

    Safety and tolerability of ORIC-101 in combination with enzalutamide

    Measured: 36 months

  7. Number of Participants with Abnormal Vital Signs

    Safety and tolerability of ORIC-101 in combination with enzalutamide

    Measured: 36 months

Secondary outcomes (11)

  1. Maximum plasma concentration (Cmax)

    PK of ORIC-101 in combination with enzalutamide

    Measured: 28 Days

  2. Minimum plasma concentration (Cmin)

    PK of ORIC-101 in combination with enzalutamide

    Measured: 36 months

  3. Time of maximum observed concentration (Tmax)

    PK of ORIC-101 in combination with enzalutamide

    Measured: 28 Days

  4. Area under the curve (AUC(0-24))

    PK of ORIC-101 in combination with enzalutamide

    Measured: 28 Days

  5. Elimination half-life (T1/2)

    PK of ORIC-101 in combination with enzalutamide

    Measured: 28 Days

  6. Circulating tumor cells (CTCs) conversion

    ≥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)

    Measured: 36 months

  7. Objective response rate (ORR)

    Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and PCWG3 criteria

    Measured: 36 months

  8. Duration of response (DOR)

    Radiographic progression using RECIST v1.1

    Measured: 36 months

  9. Progression-free survival (PFS)

    Time from first dose to first documentation of radiographic progression or death

    Measured: 36 months

  10. Overall survival (OS)

    Time from first dose to death

    Measured: 36 months

  11. Number of Participants with GR Expression by IHC

    Level of GR expression by IHC in tumor tissue samples

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2019
  2. Study start28 Oct 2019
  3. Primary completion22 Nov 2022
  4. Study completion4 Dec 2023

Why it stopped: IND Withdrawn

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Modified interval 3+3 dose escalation design, followed by dose expansion
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04033328
Sponsor's protocol ID
ORIC-101-02
Status last verified
Dec 2023
First submitted
24 Jul 2019
Last updated
15 Dec 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 38226958

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ORIC-101 and enzalutamide 40 MG oral capsule [Xtandi] in people with Prostatic Neoplasms, run by ORIC Pharmaceuticals at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: IND Withdrawn). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended Phase 2 Dose (RP2D) (time frame: 12 months). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04033328, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2023.

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