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Study Evaluating the Safety, Tolerability and Anti-Tumor Efficacy of Orellanine Treatment in Patients with Metastatic Clear-Cell or Papillary Renal Cell Carcinoma

Trial ID: NCT05287945
Oncorena is developing a potentially curative therapy for advanced kidney cancer based on orellanine. The hope is to meet an urgent and major unmet medical need. The purpose of this study is to see if orellanine treatment is safe, tolerable and effective in patients with metastatic clear-cell or papillary renal cell carcinoma. Orellanine is a highly selective organ specific natural substance found in mushrooms of the Cortinarius Family. It targets clear cell and papillary renal cell carcinoma and the proximal tubular cells in the kidneys from which these cancers originate. Orellanine does this by disrupting metabolism, causing decreased protein synthesis and subsequent apoptosis and necrosis without adversely affecting other cells in the body. With its unique mode of mechanism, it has a curative potential. In a human metastatic renal cancer in xenograft rat model, orellanine showed 90 % reduction of tumour volume within 3 days after treatment. Orellanine will initially be examined in patients with advanced kidney cancer already on dialysis. These patients have no remaining kidney function but are in great need for treatment of the metastatic disease and they may have a therapeutic anti-tumor benefit of orellanine.

Trial Details

This is a phase I/II, open-label study to investigate the safety and preliminary anti-tumor efficacy of orellanine in patients with metastatic clear-cell or papillary renal cell carcinoma. The study will include an intra-patient dose escalation phase, followed by a dose expansion phase.

This study will enroll patients with metastatic renal cell carcinoma who are in end-stage disease, dependent on hemodialysis, and for whom no conventional therapy is available or considered appropriate by the treating physician. The compound to be investigated is orellanine, a highly kidney-specific agent with promising preclinical results of tumor-eradication.

Estimated Enrollment

40 Participants

Phase

1/2

Eligibility Criteria

Participants must:

  • Be an adult 18+ years of age
  • Have 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
  • Have an ECOG performance status of 0 – 2
  • Have a life expectancy ≥3 months
  • Have acceptable hematologic 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 ≥5.9 mmol/L (~95 g/L), without transfusion within 4 weeks prior to the blood test (NOTE: Use of erythropoietin is permitted)
  • Be on chronic hemodialysis (on a consistent regimen for the previous three months, with allowance for intermittent treatments as required for volume overload)
  • Be willing and able to comply with travel requirements, scheduled visits, treatment schedule, efficacy assessments, laboratory tests, and other study procedures

Participants must not:

  • Have a diagnosis of any other malignancy within 2 years prior to enrolment (*some exceptions apply)
  • Have symptomatic, steroid-dependent, or progressive brain metastasis/metastases
  • Have had radiotherapy within 4 weeks before first dose
  • Have received systemic anti-cancer therapy within 4 weeks before first dose
  • Have received any other investigational product within 4 weeks before first dose
  • Have an uncontrolled medical condition including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements

What Will Happen in This Study

The study is divided into an accelerated dose escalation phase and a dose expansion phase. In the dose escalation phase, 6-20 patients will be enrolled, and it will consist of intra-patient dose escalation up to maximum planned dose. Orellanine is administered as an intravenous infusion (over half an hour) on the day after haemodialysis. Patients will receive orellanine on Day 2 of each four-week cycle. Patients will undergo haemodialysis on Days 1 and 3; the Day 3 haemodialysis will begin 24 ±1 hours after dosing. Patients will be scanned between Days 22 and 24, allowing alignment with a weekday schedule and providing time for analysis of response prior to the next dose.

In the dose expansion phase, additional patients will be recruited (up to a total of 20 treated at the recommended Phase 2 dose [RP2D]) to better characterize drug safety, tolerability, and preliminary efficacy.

Practical Information About the Oncorena Study of Orellanine in Kidney Cancer

Who is eligible for the study? Only patients who have certain kinds of kidney cancer (clear or papillary cell renal carcinoma). These patients must already be on dialysis and have very little ability to make urine. Orellanine will kill both normal kidney cells and cancerous kidney cells, so the treatment cannot be offered to patients with normal kidney function.

What is involved? Orellanine is given once a month into a vein over a half hour. The patient will have dialysis the day before and after this. Blood samples will be taken for lab tests before the drug is administered as a safety check and afterwards both for safety and to see how the drug is working. A CT scan will be performed once a month to see if tumors are changing size.

Where will this take place? The treatment will take place at Karolinska University Hospital in Stockholm. Since most patients do not live near this hospital, the company supporting the trial will cover all travel and lodging costs related to getting to and from the hospital. A dedicated travel agent will help to plan the visit and take care of paperwork. If the patient wants a friend or a nurse as a travel companion, that cost will also be covered.

Some questions that patients may have:

  • What about my current doctors? The doctors conducting will maintain an open line of communication with the patient’s current doctors like their oncologist, nephrologist and general practitioner; they will all be kept up to date about the patient’s progress.
  • Can I stop when I want? Yes. The patient is in the driver’s seat. Their consent is required at every point. If they want to stop participation in the study at any time, that is up to them.
  • What are the costs? The patient will not need to pay for anything related to the trial, for example any blood tests, CT scans, or getting to and from the treatment site.
  • How much is known about the drug and how safe is it? So far, the drug has only been tested in animals; this clinical trial is the first one where orellanine will be given to humans. Before patients start the trial, they will undergo a formal informed consent process that will lay out the history of this drugs development and go into detail about potential side effects. At that session, the patient will have the opportunity to talk to the study doctors about any concerns they may have and to have any questions answered.

Learn More About How Orellanine Targets Clear Renal Cell Carcinoma

How Orellanine Targets Clear Renal Cell Carcinoma

Learn More About the Long-Term Clinical Outcomes in Patients Exposed to Nephrotoxin Orellanine

Long Term Clinical Outcomes

Where is the study site?

Your patient will need to travel to the site below to participate.

Sites are located in the cities/states identified with the red pin: