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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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. Has acceptable liver laboratory values defined as:
1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤5 × ULN for patients with liver metastases
2. Total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels \>1.5 × ULN
3. For patients diagnosed with Gilbert's syndrome, total bilirubin ≤2 × ULN is acceptable.
9. Must be on chronic hemodialysis (on a consistent regimen for the previous three months, with allowance for intermittent treatments as required for volume overload).
10. 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.
11. 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.
12. For females of child-bearing potential, a negative serum pregnancy test at screening.
13. 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. Immuno-oncology therapy (IO) given in the last six (6) months prior to enrolment
4. Other systemic anti-cancer therapy within 2 weeks before first dose.
5. 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).
6. Has received any other investigational product within 4 weeks before first dose.
7. Pregnant or breastfeeding women.
8. 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.
9. QTc interval at baseline of ≥470 msec.
Primary outcome measure(s)
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
Trial sites (9)
Facility
City
Region
Status
University of California Irvine
Orange
California
Recruiting
Stanford
Palo Alto
California
Recruiting
University of California San Francisco
San Francisco
California
Recruiting
Washington University in St. Louis
St Louis
Missouri
Recruiting
University of Texas - MD Anderson Cancer Center
Houston
Texas
Recruiting
Institut de Cancerologie Gustave-Roussy
Villejuif
France
Recruiting
START Lisbon - Hospital de Santa Maria Av
Lisbon
Portugal
Recruiting
Clinica Mi Nova Alianca
Lleida
Spain
Recruiting
Karolinska University Hospital
Stockholm
Sweden
Recruiting
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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