Study of Orellanine in Metastatic Clear-Cell or Papillary Renal Cell Carcinoma

NCT05287945 | Recruiting Phase 1 DMC

• 1 other identifier: ONC001-CL-001
• Study Type: interventional
• Target: 75
• Locations: 3 countries
• Sites: 5

Brief Summary

A phase I/II, open-label, study to determine the safety and preliminary efficacy of orellanine in patients with metastatic clear-cell or papillary renal carcinoma who have failed standard-of-care therapy. All participants must have end-stage kidney disease and be receiving stable chronic hemodialysis.

Conditions

Carcinoma, Renal Cell

Outcome Measures

Primary Outcomes (7)

• Adverse events and laboratory abnormalities as graded by NCI CTCAE v5.0.

  Through study completion, approximately 1 year

• Changes in arterial blood pressure measurements

  Through study completion, approximately 1 year

• Changes in pulse rate measurements

  Through study completion, approximately 1 year

• Changes in respiratory rate measurements

  Through study completion, approximately 1 year

• Changes in temperature measurements

  Through study completion, approximately 1 year

• Changes in physical examination findings

  Through study completion, approximately 1 year

• Maximum tolerable dose of orellanine

  Through study completion, approximately 1 year

Secondary Outcomes (10)

• Efficacy of orellanine based on time to tumor response

  Through study completion, approximately 1 year.

• Efficacy of orellanine based on best overall response

  Through study completion, approximately 1 year.

• Area under the curve extrapolated to infinity

  Through study completion, approximately 1 year.

• Terminal half-life

  Through study completion, approximately 1 year.

• Partial area under the curve

  Through study completion, approximately 1 year.

Study Arms (2)

Part B - 24-Hour Exposure Cohort

EXPERIMENTAL

Participants receive orellanine (ONC175) as a 30 minute intravenous infusion once during each 28 day treatment cycle. Hemodialysis is performed the day before the infusion and again approximately 24 hours after the infusion to define the exposure period, as orellanine is eliminated primarily through dialysis. Participants will continue their regular hemodialysis schedule throughout the cycle.

Drug: Orellanine

Part B - 72 Hour Exposure Cohort

EXPERIMENTAL

Participants receive orellanine (ONC175) as a 30 minute intravenous infusion once during each 28 day treatment cycle. In this cohort, hemodialysis is performed on the morning of the infusion, and additional hemodialysis sessions occur on the following days. Replacement doses of orellanine may be administered on the days after the initial infusion, depending on the assigned dose level. Hemodialysis is performed approximately 72 hours after the initial infusion to define the extended exposure period, as orellanine is eliminated primarily through dialysis.

Drug: Orellanine

Interventions

Orellanine DRUG

Orellanine administered intravenously

Part B - 24-Hour Exposure Cohort; Part B - 72 Hour Exposure Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has provided written informed consent.
• Has a diagnosis of histologically confirmed advanced ccRCC or pRCC. No conventional therapy is available or considered appropriate by the treating physician or is declined by the patient.
• For patients in the expansion portion of the study only: Measurable disease per RECIST version 1.1 criteria.
• ECOG performance status of 0 - 2.
• Age ≥18 years.
• Life expectancy ≥3 months.
• Has acceptable haematologic laboratory values defined as:
• Neutrophils ≥1.5 × 10\^9/L, without growth factor stimulation within 3 weeks prior to the blood test;
• Platelets ≥100 × 10\^9/L;
• Haemoglobin ≥5.6 mmol/L (\~90 g/L). Use of erythropoietin or blood transfusions are permitted.
• Has acceptable liver laboratory values defined as:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN for patients with liver metastases
• Total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels \>1.5 × ULN
• For patients diagnosed with Gilbert's syndrome, total bilirubin ≤2 × ULN is acceptable.
• Must be on chronic hemodialysis (on a consistent regimen for the previous three months, with allowance for intermittent treatments as required for volume overload).

You may not qualify if:

• Diagnosis of any other malignancy within 2 years prior to enrolment, except for adequately treated basal cell or squamous cell skin cancer, superficial melanoma, or carcinoma in situ of the breast or of the cervix, or low grade (Gleason 7 or below) prostate cancer on surveillance with no plans for treatment intervention (e.g., surgery, radiation, or castration)
• Radiotherapy within 2 weeks before first dose.
• Immuno-oncology therapy (IO) given in the last six (6) months prior to enrolment
• Other systemic anti-cancer therapy within 2 weeks before first dose.
• Has not recovered from AEs due to prior anti-cancer medications to at least grade 1 by CTCAE version 5.0 (except for alopecia and grade 2 neuropathy).
• Has received any other investigational product within 4 weeks before first dose.
• Pregnant or breastfeeding women.
• Uncontrolled medical condition including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements, or would, in the opinion of the investigator, place the patient at increased risk.
• QTc interval at baseline of ≥470 msec.

Sponsors & Collaborators

• Oncorena AB: lead

Study Sites (5)

Stanford

Palo Alto, California, 94304, United States

RECRUITING

Washington University in St. Louis

St Louis, Missouri, 63130, United States

RECRUITING

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

START Lisbon - Hospital de Santa Maria Av

Lisbon, 1649-035, Portugal

RECRUITING

Karolinska University Hospital

Stockholm, Sweden

RECRUITING

Related Publications (7)

• Buvall L, Hedman H, Khramova A, Najar D, Bergwall L, Ebefors K, Sihlbom C, Lundstam S, Herrmann A, Wallentin H, Roos E, Nilsson UA, Johansson M, Tornell J, Haraldsson B, Nystrom J. Orellanine specifically targets renal clear cell carcinoma. Oncotarget. 2017 Jul 25;8(53):91085-91098. doi: 10.18632/oncotarget.19555. eCollection 2017 Oct 31.

  PMID: 29207627 BACKGROUND

• Dy GW, Gore JL, Forouzanfar MH, Naghavi M, Fitzmaurice C. Global Burden of Urologic Cancers, 1990-2013. Eur Urol. 2017 Mar;71(3):437-446. doi: 10.1016/j.eururo.2016.10.008. Epub 2016 Oct 28.

  PMID: 28029399 BACKGROUND

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Hedman H, Holmdahl J, Molne J, Ebefors K, Haraldsson B, Nystrom J. Long-term clinical outcome for patients poisoned by the fungal nephrotoxin orellanine. BMC Nephrol. 2017 Apr 3;18(1):121. doi: 10.1186/s12882-017-0533-6.

  PMID: 28372584 BACKGROUND

• Merza H, Bilusic M. Current Management Strategy for Metastatic Renal Cell Carcinoma and Future Directions. Curr Oncol Rep. 2017 Apr;19(4):27. doi: 10.1007/s11912-017-0583-8.

  PMID: 28303494 BACKGROUND

• Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

  PMID: 7165009 BACKGROUND

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan;68(1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.

  PMID: 29313949 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

orellanine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Central Study Contacts

Börje Haraldsson, M.D., Ph.D.

CONTACT

+46702679544; borje.haraldsson@oncorena.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: March 18, 2022
• Study Start: August 4, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); SE (1); PT (1)