Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Pamela Munster

Description

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.

Official Title

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

Details

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.

Keywords

Solid Tumor Paclitaxel Albumin-Bound Paclitaxel ORIC-101 Nab-paclitaxel Dose Escalation Dose Expansion

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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.

Locations

  • UCSF Helen Diller Family Comprehensive Cancer Center (Mt. Zion Campus) not yet accepting patients
    San Francisco California 94115 United States
  • Stanford Cancer Institute not yet accepting patients
    Palo Alto California 94304 United States

Lead Scientist

  • Pamela Munster
    Professor, Medicine. Authored (or co-authored) 95 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Oric Pharmaceuticals
ID
NCT03928314
Phase
Phase 1
Study Type
Interventional
Last Updated