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Study of ORIC-101 in Combination With Anticancer Therapy in Patients With Solid Tumors

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ClinicalTrials.gov Identifier: NCT03928314
Recruitment Status : Recruiting
First Posted : April 26, 2019
Last Update Posted : May 9, 2019
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 other anticancer therapies when administered to patients with advanced or metastatic solid tumors.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: ORIC-101 Drug: Nab-paclitaxel 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, uncontrolled, multicenter, dose-finding study to assess the safety and preliminary antitumor activity of ORIC-101 in combination with anticancer therapy in patients with advanced or metastatic solid tumors. The study will begin with dose finding in combination initially with nab-paclitaxel; additional dose-finding cohorts 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.

Dose expansion may further evaluate the safety of ORIC-101 at a dose selected from dose escalation.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Standard 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 Anticancer Therapy in Patients With Advanced or Metastatic Solid Tumors
Actual Study Start Date : May 2, 2019
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: Dose Escalation
ORIC-101 dosed orally, once per day, for 5 or 7 days/week in combination with the first infusion of nab-paclitaxel (100 mg/m2 on Days 1, 8, and 15) of each 28-day cycle.
Drug: ORIC-101
ORIC-101 once daily for 21 days of each 28-day cycle

Drug: Nab-paclitaxel
100 mg/m2 Days 1, 8, and 15 of each 28-day cycle

Experimental: Dose Expansion
RP2D dose
Drug: ORIC-101
ORIC-101 once daily for 21 days of each 28-day cycle

Drug: Nab-paclitaxel
100 mg/m2 Days 1, 8, and 15 of 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


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

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

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

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

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

  6. Number of Participants With Abnormal Laboratory Values [ Time Frame: 36 months ]
    Safety and tolerability of ORIC-101 in combination with nab-paclitaxel

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

  8. Number of Participants With Abnormal Vital Signs [ Time Frame: 36 months ]
    Safety and tolerability of ORIC-101 in combination with nab-paclitaxel

  9. Number of Participants With Antitumor Activity [ Time Frame: 36 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria


Other Outcome Measures:
  1. Number of Participants With GR Expression by IHC [ Time Frame: 36 months ]
    Level of GR expression by IHC in archival tumor tissue samples



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Advanced or metastatic solid tumor cancer, 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 obtained by minimally invasive 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
  • 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 core biopsies, as follows, through a procedure that is deemed to be clinically feasible and not carry significant risk (optional for participants in the intermittent dosing group at Dose Level 1; required for all other participants):

    • one pre-treatment tumor biopsy obtained prior to dosing; and
    • one post-treatment tumor biopsy during Cycle 2

Exclusion Criteria:

  • 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
  • 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)
  • Requirement for prophylactic use of granulocyte-colony stimulating factor (GCSF)
  • 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
  • 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.

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): NCT03928314


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, California
Stanford Cancer Institute Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Feriel Buchholz    650-721-4090    ferielbu@stanford.edu   
Principal Investigator: Shivaani Kummar, MD         
UCSF Helen Diller Family Comprehensive Cancer Center (Mt. Zion Campus) Not yet recruiting
San Francisco, California, United States, 94115
Contact: Claire Hooker    415-353-9535    claire.hooker@ucsf.edu   
Principal Investigator: Pamela Munster, MD         
United States, Texas
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Aracely Cavazos    210-413-3547    acavazos@nextsat.com   
Principal Investigator: Raghad Karim, MD         
United States, Virginia
Virginia Cancer Specialists, PC Not yet recruiting
Fairfax, Virginia, United States, 22031
Contact: Claudia Phillips    703-208-9268    claudia.phillips@usoncology.com   
Principal Investigator: Raymond Wadlow, 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: NCT03928314     History of Changes
Other Study ID Numbers: 101-18101
First Posted: April 26, 2019    Key Record Dates
Last Update Posted: May 9, 2019
Last Verified: April 2019

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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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Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action