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

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.

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 phase I will consist of 2 parts: an intra-patient dose escalation part, followed by a dose exposure part.. In phase II, up to 30 additional patients will be recruited and treated to better characterize drug safety, tolerability, and preliminary efficacy.

Eligibility Criteria:
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.