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

Carcinoma, Renal Cell Clinical Trial

Official title:

A Phase I/II, Open-Label, Single-Arm Study on Safety, Tolerability and Anti-Tumour Efficacy of Orellanine Treatment in Patients With Metastatic Clear-Cell or Papillary Renal Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05287945
• Other study ID #: ONC001-CL-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 4, 2023
• Est. completion date: August 2025

Study information

• Verified date: May 2024
• Source: Oncorena AB
• Contact: Jeffrey Yachnin
• Phone: +46700856708
• Email: jeffrey.yachnin[@]regionstockholm.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. The study will include an intra-patient dose escalation phase, followed by a dose expansion phase.

Description:

This is an open, non-controlled, phase I/II study evaluating the safety, tolerability, and anti-tumor efficacy of orellanine treatment in patients with metastatic clear-cell or papillary renal carcinoma. The study will include up to 50 patients. The study will consist of 2 phases: an intra-patient dose escalation phase, followed by a dose exposure phase. A safety review will be completed by the Data Review Committee after every dose in every patient in the dose escalation phase to review pharmacokinetics, safety and tolerability data. In the exposure part of the study, up to 30 additional patients will be recruited and treated at increased dose exposure to better characterize drug safety, tolerability, and preliminary efficacy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Has provided written informed consent.

2. 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.

3. For patients in the expansion portion of the study only: Measurable disease per RECIST version 1.1 criteria.

4. ECOG performance status of 0 - 2.

5. Age =18 years.

6. Life expectancy =3 months.

7. Has acceptable haematologic laboratory values defined as:

1. Neutrophils =1.5 × 10^9/L, without growth factor stimulation within 3 weeks prior to the blood test;

2. Platelets =100 × 10^9/L;

3. Haemoglobin =5.6 mmol/L (~90 g/L). Use of erythropoietin or blood transfusions are permitted.

8. Must be on chronic haemodialysis (on a consistent regimen for the previous three months, with allowance for intermittent treatments as required for volume overload).

9. The patient's treating nephrologist and oncologist agree that the prospect of loss of remaining renal function resulting from this treatment will not significantly change the patient's future and chronic dialysis treatment.

10. Female patients of child-bearing potential and male patients must agree to use 2 forms of highly effective contraception for the duration of study treatment and after the last dose of orellanine for at least 3 months for males and 6 months for females.

11. For females of child-bearing potential, a negative serum pregnancy test at screening.

12. Patients who are willing and able to comply with travel requirements, scheduled visits, treatment schedule, efficacy assessments, laboratory tests, and other study procedures.

Exclusion criteria:

1. 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)

2. Radiotherapy within 2 weeks before first dose.

3. Systemic anti-cancer therapy within 2 weeks before first dose.

4. 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).

5. Has received any other investigational product within 4 weeks before first dose.

6. Pregnant or breastfeeding women.

7. 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• Orellanine
single intravenous administration of orellanine over 30 (±5 minutes) following hemodialysis

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Oncorena AB

Country where clinical trial is conducted

Sweden, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The occurrence of dose-limiting toxicities, treatment-emergent adverse events, and serious adverse events related to orellanine		Through study completion, approximately 1 year
Primary	Maximum tolerable dose of orellanine		Through study completion, approximately 1 year
Secondary	Efficacy of orellanine based on response rate and objective response rate at the end of the second cycle with administration of orellanine at the recommended phase 2 dose		Through study completion, approximately 1 year.
Secondary	Efficacy of orellanine based on time to tumor response		Through study completion, approximately 1 year.
Secondary	Efficacy of orellanine based on best overall response		Through study completion, approximately 1 year.
Secondary	Area under the curve extrapolated to infinity		Through study completion, approximately 1 year.
Secondary	Terminal half-life		Through study completion, approximately 1 year.
Secondary	Partial area under the curve		Through study completion, approximately 1 year.
Secondary	Dose proportionality		Through study completion, approximately 1 year.
Secondary	Time to maximum plasma concentration		Through study completion, approximately 1 year.
Secondary	Maximum plasma concentration		Through study completion, approximately 1 year.
Secondary	Total body clearance		Through study completion, approximately 1 year.
Secondary	Volume of distribution		Through study completion, approximately 1 year.