A study is conducted to assess the potential clinical benefit and treatment-related toxicities of tandutinib in combination with bevacizumab for patients with recurrent glioblastoma. Forty-one recurrent, bevacizumab-naïve glioblastoma patients were recruited for the study. Treatment consisted of tandutinib 500 mg twice daily and bevacizumab 10 mg/kg every 2 weeks starting day 15. Study results showed that all patients suffered treatment-related toxicities; common grade ≥3 toxicities were hypertension (17.1%), muscle weakness (17.1%), lymphopenia (14.6%), and hypophosphatemia (9.8%). Researchers then compared the data with results from previous clinical trials assessing the clinical benefit of bevacizumab monotherapy. They concluded that tandutinib with bevacizumab was as effective but more toxic than bevacizumab monotherapy. Which of the following best describes this type of study?

Question

A study is conducted to assess the potential clinical benefit and treatment-related toxicities of tandutinib in combination with bevacizumab for patients with recurrent glioblastoma.  Forty-one recurrent, bevacizumab-naïve glioblastoma patients were recruited for the study.  Treatment consisted of tandutinib 500 mg twice daily and bevacizumab 10 mg/kg every 2 weeks starting day 15.  Study results showed that all patients suffered treatment-related toxicities; common grade ≥3 toxicities were hypertension (17.1%), muscle weakness (17.1%), lymphopenia (14.6%), and hypophosphatemia (9.8%).  Researchers then compared the data with results from previous clinical trials assessing the clinical benefit of bevacizumab monotherapy.  They concluded that tandutinib with bevacizumab was as effective but more toxic than bevacizumab monotherapy.  Which of the following best describes this type of study?

Quizplus · Accepted Answer

The clinical trials process addresses whether new treatments (eg, drugs, procedures) are effective and safe for their intended use (ie, treatment of a disease) in the target population (ie, subjects with the disease of interest). New treatments go through several research phases; some phases involve no human subjects (ie, preclinical studies) and some involve few (ie, phase I and II trials) or many (ie, phase III and IV trials) human subjects. Each of these phases has a different purpose. A phase II trial is the second step in testing a new treatment in human subjects. It assesses treatment efficacy, toxicity, adverse effects, and optimal dosing strategies in a small number of affected subjects. The results are usually compared with historic controls (eg, data obtained in prior clinical studies investigating other treatments) to establish preliminary evidence regarding relative efficacy and toxicity. In this example, the study evaluated the potential clinical benefit (ie, efficacy) and treatment-related toxicities of a new treatment (ie, tandutinib in combination with bevacizumab) in a small sample of affected subjects (ie, those with recurrent glioblastoma). The results were then compared to prior clinical trials testing conventional therapy (ie, bevacizumab monotherapy). Therefore, the example best describes a phase II trial. (Choice A) Contrary to phase I, II, III, and IV trials, which include human subjects, preclinical studies do not involve human subjects. (Choice B) A phase I trial assesses the pharmacokinetics, pharmacodynamics, and safety profile (eg, adverse events, toxicity) of a new treatment in humans. It is usually conducted on a small number of healthy subjects, but cancer-related phase I trials may involve subjects with cancer due to the inherent toxicity of treatment. However, this study evaluated the efficacy of the new treatment; drug effectiveness is not assessed during a phase I trial. (Choice D) A phase III trial assesses the safety and effectiveness of a new treatment compared to a standard treatment (or placebo); they usually involve ≥2 groups of affected subjects that are assigned to different treatment interventions. For example, a phase III study would have a treatment arm (experimental group) receiving tandutinib in combination with bevacizumab and a control arm receiving bevacizumab alone. The effectiveness and toxicity of the treatments would then be compared to determine the superior option. In contrast, this study did not have its own control group. (Choice E) A phase IV trial studies the adverse effects caused over time by a new treatment after it has been approved and is on the market. They are used to assess potential adverse effects not identified in earlier trials. Educational objective: A phase II clinical trial assesses treatment efficacy and adverse effects in a small number of affected subjects (ie, those with the disease of interest). The results are often compared with those of previous clinical trials (ie, historic controls) to determine the potential benefit of the new treatment. __________ References: Key concepts of clinical trials: a narrative review. (http://www.ncbi.nlm.nih.gov/pubmed/21904102)

A Study Is Conducted to Assess the Potential Clinical Benefit