US-based clinical stage biopharmaceutical firm Rexahn Pharmaceuticals has started a multi-centre Phase IIa clinical proof-of-concept trial to evaluate the safety and efficacy of Archexin in patients with metastatic renal cell carcinoma (RCC).
The trial is designed to assess the efficacy of Archexin in combination with everolimus (Afinitor) to treat metastatic RCC patients and will be carried out in two stages.
The US Food and Drug Administration (FDA) has already granted orphan drug designation to Archexin for RCC indication.
In the first stage of the trial, there will be dose ranging with up to three groups of three RCC patients to determine its maximum tolerated dose in combination with everolimus.
The company said that the target dose of Archexin is expected to be no more than 250mg/m2 per day based on previous clinical data.
The decision to enrol the next group of patients and increase the dose will be made after completion of the first 21 day cycle of treatment.
Patient evaluations in the trial will comprise safety, pharmacokinetics, laboratory and physical exams.
Thirty RCC patients will be given either Archexin in combination with everolimus or everolimus alone, in a ratio of 2:1, once the maximum tolerated dose of Archexin in combination with everolimus has been determined.
The primary endpoint in the trial will be the percentage of progression free patients, following eight cycles of therapy.
In the trial, patients will be scanned for the evaluation of tumour progression after every two cycles of therapy.
Secondary endpoints in the trial include pharmacokinetic profile, incidence of adverse events, changes in clinical laboratory tests and vital signs over time, tumour response, duration of response, time to response, and response rate.
Exploratory endpoints will comprise blood levels of AKT pathway biomarkers, tumour apoptosis biomarkers or other relevant biomarkers.
Rexahn chief executive officer Peter Suzdak said: "The combination of strong scientific data, unmet clinical need, and our Orphan Drug Designation were all driving factors for choosing this indication."
Archexin is a specific inhibitor of the cancer cell signalling protein Akt-1 and its activated form has been shown to be involved in cancer cell growth, survival, angiogenesis, and drug-resistance.
A unique anti-sense drug candidate that specifically inhibits the cancer cell signaling protein Akt-1, Archexin has shown to both inhibit the growth of human renal cell carcinoma cell lines and exhibit a longer survival benefit in the human renal cell carcinoma animal xenograft model.
In addition, Archexin also exhibits additive anti-tumour effect when combined with other cancer drugs in inhibiting the growth of human RRC cells in tissue culture and may have broad therapeutic potential across multiple types of cancer.
Image: Micrograph of the most common type of renal cell carcinoma (clear cell) on right of the image; non-tumour kidney is on the left of the image. Photo: courtesy of Nephron.