Clinical trial NCT04169711: Study of ARO-HIF2 in Patients With Advanced Clear Cell Renal Cell Carcinoma
Official title: A Phase 1b Dose-Finding Study of ARO-HIF2 in Patients With Advanced Clear Cell Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Clear Cell Renal Cell Carcinoma
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-11-20
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficacy of ARO-HIF2 injection (also referred to as ARO-HIF2) and to determine the recommended Phase 2 dose in the treatment of patients with advanced clear cell renal cell carcinoma (ccRCC).


Eligibility criteria: Inclusion Criteria:

* Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding and must be willing to use contraception
* Willing to provide written informed consent and to comply with study requirements
* Histologically confirmed locally advanced or metastatic clear cell renal cell carcinoma that has progressed during or after at least two prior therapeutic regimens which must include vascular endothelial growth factor (VEGF)-targeted therapy and checkpoint inhibitor therapy or that has otherwise failed such therapies, is measurable disease per RECIST 1.1 criteria, is biopsy accessible
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Estimated life expectancy of longer than 3 months
* Adequate organ function at screening

Exclusion Criteria:

* History of untreated brain metastasis or leptomeningeal disease or spinal cord compression
* Failure to recover from reversible effects of prior anti-cancer therapy
* Has received systemic therapy or radiation therapy within 2 weeks prior to first dose
* History of solid organ or stem cell transplantation
* Current use of anti-VEGF or mammalian target of rapamycin (mTOR) agents, or chronic immunosuppressive therapy
* Any prior use of hypoxia inducible factor 2 (HIF2) inhibitors within 6 months prior to first dose
* Current use of immune checkpoint inhibitors
* Use of an investigational agent or device within 2 weeks prior to dosing, or current participation in an investigational study
* Known HIV, hepatitis B or hepatitis C
* History of other clinically meaningful disease
* Major surgery within 4 weeks of Screening
* Active malignancy requiring therapy other than ccRCC within 3 years of study entry

Note: Other eligibility criteria may apply per protocol.

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment
timeFrame: Up to 2 years from first dose
Secondary outcomes:
measure: Pharmacokinetics (PK) of ARO-HIF2: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: PK of ARO-HIF2: Time to Maximum Plasma Concentration (Tmax)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: PK of ARO-HIF2: Area Under the Plasma Concentration Versus Time Curve from Zero to 4 Hours (AUC0-4)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: PK of ARO-HIF2: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: PK of ARO-HIF2: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Measurable Concentration at a Time=t, Using a Specified Trapezoidal Rule (AUC0-t)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: PK of ARO-HIF2: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: PK of ARO-HIF2: Terminal Elimination Half-Life (t1/2)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: Systemic Clearance Derived From Intravenous Dose/Area Under the Plasma Concentration Versus Time Curve (CL)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: Amount of Drug Excreted in the Urine Over One Dosing Interval Through 4 Hours Post- Dose (Ae, 0-4)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: Renal Clearance Calculated by Ae, 0-4 h/AUC0-4h (CLR)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: Fraction Excreted (or Equivalently the Percent of Dose Excreted) in the Urine, Calculated by 100 X (Ae, 0-4 h/Dose)
timeFrame: Up to Week 2: predose and up to 48 hours postdose
measure: Overall Response Rate
timeFrame: Baseline until disease progression, up to 2 years
measure: Duration of Response
timeFrame: Baseline until disease progression, up to 2 years
measure: Time to Response
timeFrame: Baseline until disease progression, up to 2 years
measure: Progression Free Survival
timeFrame: up to 2 years
measure: Overall Survival
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
Study officials:
References: