A Phase II Multicentre, Open-Label, Proof-of-Concept Study of Tasquinimod in Hepatocellular, Ovarian, Renal Cell, and Gastric Cancers
verfasst von:
Bernard Escudier, Sandrine Faivre, Eric Van Cutsem, Nathalie Germann, Jean-Christophe Pouget, Ruth Plummer, Ignace Vergote, Fiona Thistlethwaite, Georg A. Bjarnason, Robert Jones, Helen Mackay, Julien Edeline, Laetitia Fartoux, Hal Hirte, Amit Oza
Tasquinimod is a small molecule with immunomodulatory, anti-angiogenic, and anti-metastatic properties that targets the tumor microenvironment. This study aimed to obtain a clinical proof of concept that tasquinimod was active and tolerable in patients with advanced solid tumors.
Patients and Methods
This early stopping design, open-label, proof-of-concept clinical trial evaluated the clinical activity of tasquinimod in four independent cohorts of patients with advanced hepatocellular (n = 53), ovarian (n = 55), renal cell (n = 38), and gastric (n = 21) cancers. Tasquinimod was given orally every day (0.5 mg/day for at least 2 weeks, with dose increase to 1 mg/day) until radiological progression according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria, intolerable toxicity, or patient withdrawal. The primary efficacy endpoint was progression-free survival (PFS) rate according to RECIST 1.1 by central assessment.
Results
Interim futility analyses at 8 weeks (6 weeks for the gastric cancer cohort) found adequate clinical activity of tasquinimod only in the hepatocellular cohort and recruitment to the other three cohorts was stopped. PFS rates were 26.9% at 16 weeks, 7.3% at 24 weeks, 13.2% at 16 weeks, and 9.5% at 12 weeks, respectively, in hepatocellular, ovarian, renal cell, and gastric cancer cohorts. The pre-defined PFS threshold was not reached in the hepatocellular cancer cohort at the second stage of the trial. The most common treatment-related adverse events were fatigue (48.5%), nausea (34.1%), decreased appetite (31.7%), and vomiting (24.6%).
Conclusions
This study failed to demonstrate clinical activity of tasquinimod in heavily pre-treated patients with advanced hepatocellular, ovarian, renal cell, and gastric cancer.
Trial registration
NCT01743469.
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A Phase II Multicentre, Open-Label, Proof-of-Concept Study of Tasquinimod in Hepatocellular, Ovarian, Renal Cell, and Gastric Cancers
verfasst von
Bernard Escudier Sandrine Faivre Eric Van Cutsem Nathalie Germann Jean-Christophe Pouget Ruth Plummer Ignace Vergote Fiona Thistlethwaite Georg A. Bjarnason Robert Jones Helen Mackay Julien Edeline Laetitia Fartoux Hal Hirte Amit Oza
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