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Solid TumorPhase 1NCT03928314

Study of ORIC-101 in Combination With Anticancer Therapy

A Phase 1 study testing ORIC-101 and Nab-paclitaxel in people with Solid Tumor, run by ORIC Pharmaceuticals at 12 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 nab-paclitaxel or other anticancer therapies when administered to patients with advanced or metastatic solid tumors. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
ORIC-101 and Nab-paclitaxel
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
12 sitesUnited States
Study dates
2 May 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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Advanced or metastatic solid tumor, with the exception of neuroendocrine tumors that secrete adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone (CRH), for which no alternative effective standard therapy is available or for which standard therapy is considered unsuitable or intolerable
  • Measurable disease (ie, presenting with at least one measurable lesion per RECIST 1.1)
  • Radiographic evidence of a lesion that may be safely biopsied by core needle biopsy
  • For patients with treated, stable CNS metastases that are asymptomatic: no evidence of progression for at least 4 weeks after CNS-directed treatment as determined by clinical examination and brain imaging. Patients must not require steroids
  • ECOG performance status 0 or 1
  • Life expectancy of at least 3 months
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  • Available archival FFPE tissue for submission to central laboratory
  • Male: must agree to birth control requirements and Female: not pregnant, breastfeeding, and meets requirements regarding women of child-bearing potential
  • Capable of giving signed informed consent
  • Agreement and ability to undergo two on-study biopsies, as follows, through a procedure that is deemed to be clinically feasible and not carry significant risk:
  • one pre-treatment tumor biopsy obtained prior to dosing; and
  • one post-treatment tumor biopsy during Cycle 2

Who cannot join

  • Any other current or active malignancy
  • Grade 2 or higher peripheral neuropathy
  • Known human immunodeficiency virus (HIV) infection
  • Major surgery within 21 days prior to Cycle 1 Day 1 or incomplete recovery from adverse effects resulting from such procedure
  • Females: history of unexplained vaginal bleeding in the 8 weeks prior to planned study treatment
  • History of Cushing's syndrome or adrenal insufficiency
Show all 68Show fewer
  • Other concurrent serious uncontrolled medical, psychological, or addictive conditions that may interfere with planned study treatment or adherence to protocol
  • Prior or current treatment with ORIC-101 or any other GR antagonist (eg, mifepristone, relacorilant)
  • Current or requirement for chronic use of systemic corticosteroids with the exception of inhaled, topical, intraocular, intranasal, or intraarticular corticosteroids.
  • Current or expected on-study treatment with specified strong CYP3A4 inhibitors or inducers
  • Treatment with another investigational medicinal product (within 3 weeks prior to starting study treatment)
  • Receiving any other anticancer therapy, radiotherapy, or herbal (alternative) medicines within 7 days prior to starting study treatment
  • Use of hormone replacement therapy by females
  • Current enrollment in any other therapeutic clinical study involving an investigational study treatment
  • Presence of Hepatitis B surface antigen at screening
  • Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment
  • Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment
  • Unacceptable laboratory 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)
  • Albumin <3.0 g/dL (30 g/L)
  • AST (SGOT) or ALT(SGPT) >2.5 × ULN
  • AST (SGOT) or ALT (SGPT) >2.5 and ≤5.0 × ULN is acceptable for patients with liver metastases
  • Bilirubin >1.5 × ULN:
  • Isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35% of total bilirubin
  • Bilirubin >1.5 and ≤3.0 × ULN is acceptable for patients with known Gilbert's disease
  • QTcF >450 msec for males; QTcF >470 msec for females; or QTcF >480 msec for those with bundle branch block (BBB)
  • Consumption of Seville oranges, grapefruit or grapefruit juice, pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices containing these fruits from 10 days before the start of study treatment
  • Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.
  • Any other condition or circumstance (eg, 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.
  • Expansion Cohorts Part II Inclusion Criteria:
  • PDAC: Advanced or metastatic PDAC previously treated with and progressed on a fluoropyrimidine-based regimen and a taxane-containing chemotherapy regimen (eg, gemcitabine + nab-paclitaxel). Pancreatic neuroendocrine tumors, lymphoma of the pancreas, acinar pancreatic cancer, or ampullary cancer are not eligible.
  • Ovarian Cancer: Advanced or metastatic high grade serous or endometrioid epithelial ovarian, primary peritoneal, fallopian tube cancer or ovarian carcinosarcoma, previously treated with and progressed on a taxane-containing chemotherapy regimen; clear cell, mucinous and borderline histologic subtypes are not eligible; must have received at least one line of therapy with evidence of cancer progression within 6 months after the last dose of platinum-based therapy (ie, having a platinum-free interval of <6 months [platinum resistant]), or progressive disease during or immediately after primary platinum-therapy, (ie, platinum refractory).
  • TNBC: Advanced or metastatic ER-negative, PR-negative, HER2-negative primary breast cancer previously treated and progressed on a taxane-based chemotherapy regimen; no previous or synchronous second breast cancer, unless also confirmed ER-, PR- and HER2-negative; must have received at least one line of therapy in the metastatic setting.
  • Other Solid Tumor: Other advanced or metastatic solid tumor previously treated with and progressed on a taxane-based chemotherapy regimen, with the exception of metastatic colorectal cancer, primary brain tumors, and neuroendocrine tumors that secrete ACTH or CRH; must have received no more than 4 prior lines of cytotoxic or myelosuppressive therapy
  • Other Key Inclusion Criteria:
  • At least 18 years of age
  • ECOG performance status 0 or 1
  • Measurable disease as assessed centrally using RECIST 1.1
  • Treated, stable CNS metastases must be asymptomatic and must not require steroids
  • Agreement and ability to undergo two on-study biopsies, one pre-treatment obtained prior to dosing and during Cycle 2
  • 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)
  • Albumin ≥3.0 g/dL
  • 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
  • Ability to swallow ORIC-101 intact without chewing or crushing the capsules or tablets
  • Adequate gastrointestinal absorption. If the patient has undergone gastric bypass surgery and/or surgery of gastrointestinal or hepatobiliary tract, the patient must demonstrate adequate absorption as evidenced by albumin ≥3.0 g/dL, controlled pancreatic insufficiency (if present), and lack of evidence of malabsorption
  • Expansion Cohorts Part II Exclusion Criteria:
  • Any other current or active malignancy
  • Prior or current treatment with ORIC-101 or any other GR antagonist (eg, mifepristone, relacorilant)
  • Concurrent treatment with any other anticancer therapy including chemotherapy, hormonal therapy, immunotherapy, radiotherapy, chemoembolization, targeted therapy, or an investigational agent within 28 days prior to Cycle 1 Day 1
  • Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or incomplete recovery from adverse effects resulting from such procedures; palliative radiotherapy within 1 week of Cycle 1 Day 1
  • Systemic, inhaled, or prescription strength topical corticosteroids within 21 days prior to Cycle 1 Day 1; short courses (≤5 days) for non-cancer-related reasons are allowed if clinically required
  • Grade 2 (moderate) or higher peripheral neuropathy per CTCAE v5.0; patients with mild peripheral neuropathy may be eligible at the discretion of the investigator in consultation with ORIC
  • All other toxicities from prior therapy (except alopecia) that have not resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 ≤ Grade 1
  • Females: history of unexplained vaginal bleeding in the 8 weeks prior to Cycle 1 Day 1 (given potential for ORIC-101 to exacerbate such bleeding)
  • Females: use of hormone replacement therapy; hormone replacement therapy must be discontinued to allow for confirmation of postmenopausal status
  • History of Cushing's syndrome or adrenal insufficiency
  • Current (within 10 days prior to Cycle 1 Day 1) or expected on-study treatment with specified strong CYP3A4 inhibitors or inducers
  • Known human immunodeficiency virus (HIV) infection, unless patient is healthy and has a low risk of AIDS-related outcomes
  • Presence of Hepatitis B surface antigen (HBsAg) at screening
  • Positive Hepatitis C (HCVAb) antibody test result at screening or within 3 months prior to Cycle 1 Day 1. NOTE: Patients with positive HCVAb due to prior resolved disease can be enrolled if a confirmatory negative Hepatitis C RNA test is obtained
  • Positive Hepatitis C RNA test result at screening or within 3 months prior to Cycle 1 Day 1. NOTE: Test is optional and patients with negative HCVAb test are not required to also undergo Hepatitis C RNA testing

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • University of Colorado - PPDS

    Aurora, Colorado, 80045

  • Mary Crowley Cancer Research Centers - Medical City

    Dallas, Texas, 75231

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Florida Cancer Specialists & Research Institute

    Lake Mary, Florida, 32746

  • Tennessee Oncology NASH - SCRI - PPDS

    Nashville, Tennessee, 37203

  • Stanford Cancer Institute

    Palo Alto, California, 94304

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of Utah - Huntsman Cancer Institute - PPDS

    Salt Lake City, Utah, 84112

  • NEXT Oncology

    San Antonio, Texas, 78229

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Florida Cancer Specialists & Research Institute

    Sarasota, Florida, 34232

Other trials in United States

About this study

Official title: An Open-label Phase 1b Study of ORIC-101 in Combination With Anticancer Therapy in Patients With Advanced or Metastatic Solid Tumors

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 nab-paclitaxel or other anticancer therapies when administered to patients with advanced or metastatic solid tumors.

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, uncontrolled, multicenter, dose-finding study to assess the safety and preliminary antitumor activity of ORIC-101 in combination with nab-paclitaxel or other anticancer therapy in patients with advanced or metastatic solid tumors. The study will begin with dose finding in combination initially with nab-paclitaxel in patients with various solid tumors (Part I); additional dose expansion cohorts in specific tumor types with nab-paclitaxel (Part II) or with other anticancer therapies may be evaluated through protocol amendment(s).

The study will first evaluate intermittent administration (5 days on, 2 days off for 21 days) of ORIC-101 followed by continuous administration (daily for 21 days) in combination with nab-paclitaxel using a standard 3+3 dose escalation design.

In Part II, patients will be enrolled across four cohorts of advanced or metastatic disease:

  • pancreatic ductal adenocarcinoma (PDAC)
  • ovarian cancer
  • triple negative breast cancer (TNBC)
  • other solid tumors
Conditions
Solid Tumor
Being tested
ORIC-101, Nab-paclitaxel
Keywords
GR antagonist, Glucocorticoid receptor antagonist

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, 5 or 7 days/week, for 21 days of each 28-day cycle

  • Nab-paclitaxelDrug

    75 or 100 mg/m2 Days 1, 8, and 15 of each 28-day cycle

Study groups in NCT03928314
Study groupRoleWhat they receive
Dose Escalation (Part I)ExperimentalORIC-101 dosed orally, once per day, for 5 or 7 days/week in combination with nab-paclitaxel (75 or 100 mg/m2 on Days 1, 8, and 15) of each 28-day cycle.
Receives: Drug: ORIC-101; Drug: Nab-paclitaxel
Dose Expansion (Part II)ExperimentalRP2D dose
Receives: Drug: ORIC-101; Drug: Nab-paclitaxel

What is being measured

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

  1. Part I: Recommended Phase 2 Dose (RP2D)

    RP2D as determined by 3+3 dose escalation design

    Measured: 12 months

  2. Part II: Objective Response Rate (ORR)

    Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and assessed by Blinded Independent Central Review (BICR)

    Measured: 18 months

Secondary outcomes (12)

  1. Part I: Maximum plasma concentration (Cmax)

    PK of ORIC-101 in combination with nab-paclitaxel

    Measured: 28 Days

  2. Part I: Time of maximum observed concentration (Tmax)

    PK of ORIC-101 in combination with nab-paclitaxel

    Measured: 28 Days

  3. Part I: Area under the curve (AUC(0-t))

    PK of ORIC-101 in combination with nab-paclitaxel

    Measured: 28 Days

  4. Parts I and II: Number of Participants with Adverse Events

    Safety and tolerability of ORIC-101 in combination with nab-paclitaxel

    Measured: 36 months

  5. Parts I and II: Number of Participants with Abnormal Laboratory Values

    Safety and tolerability of ORIC-101 in combination with nab-paclitaxel

    Measured: 36 months

  6. Parts I and II: Number of Participants with Abnormal 12-lead ECG

    Safety and tolerability of ORIC-101 in combination with nab-paclitaxel

    Measured: 36 months

  7. Parts I and II: Number of Participants with Abnormal Vital Signs

    Safety and tolerability of ORIC-101 in combination with nab-paclitaxel

    Measured: 36 months

  8. Part I: Number of Participants with Antitumor Activity

    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria

    Measured: 36 months

  9. Part II: Duration of Response (DOR)

    Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and assessed by Blinded Independent Central Review (BICR)

    Measured: 36 months

  10. Part II: Progression-Free Survival (PFS)

    Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and assessed by Blinded Independent Central Review (BICR)

    Measured: 36 months

  11. Part II: Overall Survival (OS)

    Time from first dose of ORIC-101 in combination with nab-paclitaxel to death

    Measured: 36 months

  12. Part II: Investigator-assessed ORR

    Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

    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 Apr 2019
  2. Study start2 May 2019
  3. Primary completion22 Sep 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
Standard 3+3 dose escalation design, followed by dose expansion
Masking
None (open label)
Enrolment
83 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03928314
Sponsor's protocol ID
101-18101
Status last verified
Dec 2023
First submitted
19 Apr 2019
Last updated
15 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Chen CT, Khanna V, Kummar S, Abdul-Karim RM, Sommerhalder D, Tolcher AW, Ueno NT, Davis SL, Orr DW, Hamilton E, Patel MR, Spira AI, Jauhari S, Florou V, Duff M, Xu R, Wang J, Barkund SR, Zhou H, Pankov A, Kong W, Jahchan NS, Jackson EL, Sun JD, Junttila MR, Multani PS, Daemen A, Chow Maneval E, Munster PN. ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors. Cancer Res Commun. 2024 Sep 1;4(9):2415-2426. doi: 10.1158/2767-9764.CRC-24-0115.

    PubMed 39177285

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ORIC-101 and Nab-paclitaxel in people with Solid Tumor, run by ORIC Pharmaceuticals at 12 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 12 inclusion and 68 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 12 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?

Part I: Recommended Phase 2 Dose (RP2D) (time frame: 12 months). The study lists 2 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 NCT03928314, 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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