Pilot Studies: When Efficacy Is Not the Primary Question

Pilot studies can answer questions about whether a given trial design is feasible within the bounds of the National Clinical Trials Network and/or the NCI Community Oncology Research Program. They can tell us whether patients find a given intervention or approach acceptable, or whether we can enroll the right patients at the right rate of accrual.

Typically, they’re also looking for preliminary signals about the efficacy of an intervention, but they’re designed primarily to let us know whether – and how – we can successfully conduct the larger-scale trial that could give us those more definitive efficacy answers.

The results of one SWOG pilot study, S1820, have just been published in the journal Cancer. Subtitled “a feasibility and preliminary efficacy study,” S1820 was a randomized trial of a behavioral intervention designed to help ease symptoms of bowel dysfunction in people who have undergone rectal cancer surgery.

Many survivors of rectal cancer find that after their surgery, bowel dysfunction symptoms persist months and even years later at a level that degrades their quality of life and limits their social activities. 

Led by Dr. Virginia Sun, SWOG executive officer for research in palliative and end-of-life care and cancer survivorship, S1820 was a randomized pilot trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention, which was designed to help survivors manage their diet in a way that can reduce their bowel symptoms. 

The intervention was administered through 10 phone sessions with trained health coaches, spread over four months, and it incorporated a food and symptom diary that helped rectal cancer survivors track associations between the foods they ate and their bowel symptoms.

S1820 participants were randomized to this AIMS-RC intervention or to a control arm on which they were given educational information about general cancer survivorship topics and also had 10 telephone sessions with health coaches over four months.

In assessing the trial’s primary endpoint, which was a standard measure of bowel function, the study team found no statistically significant difference between arms, although they did see intervention arm benefits in other measures of bowel function.

Importantly, they did confirm the feasibility of conducting such a study within SWOG and they learned that the tested intervention was highly acceptable to participants. They also demonstrated it was possible to rapidly accrue to such trials, enrolling 117 participants to S1820 in just over two years. These results are likely to inform the development of larger, more definitive trials of this and other interventions meant to alleviate such symptoms in cancer survivors.

With S1820 reporting out, SWOG has two other key pilot studies still underway.

• The S2101 BiCaZO trial is a pilot study for the planned ImmunoMATCH precision medicine trial. One of S2101’s multiple primary objectives is to assess the efficacy of a cabozantinib-nivolumab combination in patients with advanced melanoma or head-and-neck cancer, but its other primary objectives are to test whether it’s feasible to use the two iMATCH assays to assign every enrolled patient to a treatment subgroup in 21 days or less. This level of performance is central to ImmunoMATCH’s design, so it’s critical to validate whether such performance is feasible. S2101 recently reopened to accrual after an enrollment pause, and the team is now working to complete accrual to Stage I of the study.
• S1933 is a pilot study of hypofractionated radiotherapy followed by atezolizumab consolidation in patients who have Stage II or III non-small cell lung cancer and have borderline performance status. The study assesses the efficacy of this combination, but its primary objective is to evaluate the safety of the treatment. If the pilot demonstrates this combination is safe in these patients, the hope is to conduct a larger, randomized, more definitive study of this approach.

SWOG studies do not all have identical goals, and it’s important we measure success using the right yardstick. With our pilot studies, the yardstick is typically not whether the intervention provided a clear benefit but whether – and how – we can conduct the right trial later.