Metastatic Clear Cell Renal Cell Carcinoma (ccRCC) or papillary renal cell carcinoma (pRCC) and with End-Stage Renal Disease (ESRD) MedDRA version: 21.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 22.0 Level: HLT Classification code 10038443 Term: Renal failure and impairment System Organ Class: 100000004857
Conditions
Interventions
Product Name: Orellanine
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: Orellanine
CAS Number: 37338-80-0
Other descriptive name: Orellanine
Concentration un
Sponsors
Oncorena AB
Eligibility
Sex/Gender
All
Inclusion 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 Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 2. 5. Age >18 years 6. Life expectancy >3 months 7. Has acceptable haematologic laboratory values defined as: a. Neutrophils =1.5 x 109/L, without growth factor stimulation within 3 weeks prior to the blood test; b. Platelets =100 × 109/L; c. Haemoglobin =5.9 mmol/L (~95 g/L), without transfusion within 4 weeks prior to the blood test. Use of erythropoietin is permitted. 8. Must be on chronic haemodialysis (on a consistent regimen for the previous 3 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 patients' future and chronic dialysis treatment. 10. Female patients of child-bearing potential and male patients must agree to use two highly effective forms of 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 childbearing potential, a negative serum pregnancy test at screening 12. Patients who are willing and able to comply with travel requirements, schedule visits, treatment schedule, efficacy assessments, laboratory tests, and other study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
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. Has symptomatic, steroid-dependent, or progressive brain metastasis/metastases. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during trial screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of trial treatment. 3. Radiotherapy within 4 weeks before first dose. 4. Systemic anti-cancer therapy within 4 weeks before first dose. 5. Has not recovered from adverse events (AEs) due to prior anti cancer medications to at least grade 1 by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (except for alopecia and grade 2 neuropathy). 6. Has received any other investigational product (IP) 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The combined primary objective of this study is to evaluate the safety and tolerability and to determine the maximum tolerable dose (MTD) of orellanine in patients with metastatic RCC with ESRD who are on chronic haemodialysis and who have failed standard of care treatment. ;Secondary Objective: - The pharmacokinetic (PK) profile of orellanine. - To assess the efficacy of orellanine in treating patients with metastatic RCC who have failed standard of care treatment with respect to overall response rate.;Primary end point(s): Adverse Events (AEs) Terminology Criteria for Adverse Events (CTCAE) v5.0, vital signs (BP, pulse rate, respiratory rate, and temperature), and physical examination findings (including ECG). Dose Limiting Toxicities Dose levels to define Maximum Tolerable Dose and Recommended Phase 2 Dose.;Timepoint(s) of evaluation of this end point: During the entire study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Evaluated based on Blinded Independent Central Review and investigator assessment (per RECIST) v1.1 based on CT scans and includes: response rate and ORR at the end of the second cycle with administration of orellanine at RP2D, best overall response, and time to tumour response (TTR). Patients in the dose expansion phase who are not evaluable at the end of the second cycle will be replaced for analysis of this endpoint. All partial responses (PR) and complete responses (CR) will be confirmed with a second scan at least four weeks after initial documentation of response. Additional secondary endpoints: Patients in the dose expansion phase of the study will be followed for PFS and OS. PK parameters: Area under the curve from time 0 to time t (AUC0-t), AUC from time 0 to infinity (AUC0-8), terminal half-life (T½), maximum plasma concentration (Cmax), time to Cmax (Tmax), dose proportionality (based on AUC and Cmax), total body clearance (CL) and Volume of distribution (Vd).;Timepoint(s) of evaluation of this end point: During the entire study | — |
Countries
Sweden
Contacts
Public ContactSuzanne Jones
Theradex (Europe) Ltd.
Outcome results
None listed