STAR-OLZ Noted as First Product in Trials Using Total Control Primary End Point

A clinical trial of the transdermal delivery system (TDS) of olanzapine, STAR-OLZ, for reduction of chemotherapy-induced nausea and vomiting (CINV) will be the first ever to use the primary end point of total control, announced the agent’s developer, Starton Therapeutics, in a press release.¹

With the use of STAR-OLZ, patients will be administered the multi-day TDS of olanzapine, a powerful antiemetic that is not currently approved for indications of nausea or vomiting.

“STAR-OLZ represents the first product to be developed for FDA approval using the total control primary end point, which we believe will generate more clinically meaningful data for evaluating CINV treatment than prior trials for currently approved therapies,” Jamie Oliver, Chief Medical Officer of Starton Therapeutics, said in a statement. “Total Control is a measure of no nausea, no vomiting, and no rescue medications; existing antiemetics have been approved using a complete response (CR) end point which only measures vomiting and rescue medications.”

In a small study of patients with advanced cancer who were experiencing persistent nausea and vomiting in the absence of chemotherapy or radiation, 16 men and 14 women were given 5 mg of oral olanzapine or placebo daily for 7 days. Using a numeric rating scale, patients in the placebo group had a media nausea score of 9 out of 10, whereas patients in the olanzapine group had a score of 2 out of 10. After 1 week of treatment, patients being treated with olanzapine had an 8-point reduction in nausea scores (95% CI, 7-8).²

Patients in the olanzapine group reported less emesis, less frequent use of other antiemetic drugs, better appetite, and less sedation. No patients receiving olanzapine reported excess sedation or any adverse event.

Following these data, investigators conducted the largest and most comprehensive meta-analysis on the use of olanzapine in CINV. Across 13 studies, 58% (553/952) of people who were treated with olanzapine in the delayed interval of 24 to 120 hours after receiving chemotherapy did not report nausea compared with 38% (300/793) of people who did report nausea from the control group.

During the acute phase of the trial (0-24 hours), 73 people treated with olanzapine reported no nausea versus 57% from the control group. While more people reported no nausea, the CR was similar across acute, delayed, and overall intervals for both olanzapine and control groups. This information gathered shows the limitations of the CR endpoint in evaluating CINV treatments.

References

1. Starton Therapeutics Phase 2 TROPIC-I Clinical Study will be First to Use Total Control Primary Endpoint in Superiority Study. News Release. Published June 16, 2021. Accessed June 22, 2021. https://bit.ly/2UyLLZ2

2. Navari RM, Pywell CM, Le-Rademacher JG, White P, Dodge AB, Albany C, Loprinzi CL. Olanzapine for the Treatment of Advanced Cancer-Related Chronic Nausea and/or Vomiting. JAMA Oncology. doi:10.1001/jamaoncol.2020.1052

3. Chow R, Herrstedt J, Aapro M, et al. Olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting: a systematic review, meta-analysis, cumulative meta-analysis and fragility assessment of the literature. Support Care Cancer. 2021;29(7):3439-3459. doi:10.1007/s00520-020-0