Modeling Adverse Event Risk Prediction: S2013 and S1501 Are Reopen to Enrollment!

S2013, the I-CHECKIT trial, opens Cohort 2 to NCORP enrollment
This observational study, aiming to develop and validate a risk prediction model for grade 3+ immune-related adverse events (irAEs) in patients on immune checkpoint inhibitor-based therapy, was temporarily closed earlier this year after reaching its Cohort 1 accrual target of 2,062 participants.

The protocol has been revised, and the trial was reactivated on November 15th. Cohort 1 has closed, and a new cohort, Cohort 2, has been added.

Cohort 1 enrolled patients with solid tumors who were about to start therapy with an immune checkpoint inhibitor (ICI) alone. The new Cohort 2 is enrolling patients who are about to start therapy with an ICI plus chemotherapy. 

The revised protocol includes a list of allowable chemo + ICI regimens for these patients – for lung cancer (small cell or non-small cell), triple-negative breast cancer, or gastroesophageal cancer. Cohort 2 has an accrual goal of 1,547 participants.

With this revision of S2013 and the opening of Cohort 2, only NCORP and Minority/Underserved NCORP sites under the membership of an NCORP Research Base may now enroll participants.

NCTN sites (that is, non-NCORP sites) can no longer enroll to S2013, although NCTN sites that previously enrolled to the trial will continue with required follow-up for those participants. 

Cohort 2 of the trial has also added an additional objective – exploring the association of dietary fiber intake with severe irAEs from ICI-based therapy. To this end, newly enrolled participants will now complete the Dietary Screener Questionnaire at registration and at the four week timepoint.

Overall, S2013’s burden on sites and participants has been reduced, as some of the Cohort 1 requirements have been trimmed back for Cohort 2. Specifically, the Feasibility Questionnaire and tissue submission for banking are no longer required, and the PROMIS Cognitive Function questionnaire now needs to be completed at only two time points.

S2013 is co-led by Drs. Krishna Gunturu and Dawn Hershman.

S1501: Arm 3 reopens, while Arms 1 and 2 close 
Our S1501 study of cancer treatment cardiotoxicity closed temporarily earlier this year for a planned redesign, after it was determined the study’s event rate didn’t justify a randomized intervention. 

After an interim analysis and redesign, the trial has reopened. 

It’s now an observational study to establish the incidence of cardiac dysfunction and cardiac events – and to develop a model to predict cardiac dysfunction risk – in patients taking trastuzumab for breast cancer who are at high risk for cardiotoxicity.

The trial’s Arm 1 (intervention with carvedilol) and Arm 2 (no prophylaxis) have closed to accrual, although patients already enrolled to those arms may continue their protocol-specified therapy.

Arm 3 (non-randomized observation) has reopened, now needing roughly 180 additional participants to reach its accrual goal of 336. It’s enrolling patients with metastatic HER2-positive breast cancer who are also taking a beta blocker, angiotensin receptor blocker (ARB), or angiotensin-converting enzyme (ACE) inhibitor.

With the closure of Arms 1 and 2, real-time echocardiogram reads are no longer needed, and data collection and study administration should be simpler for sites. Overall, the S1501 redesign should allow for faster study completion, while still generating valuable, potentially practice-changing, data about cardiotoxicity incidence and risk.

Drs. Justin Floyd and Monika Leja chair the S1501 study.
 

The new protocol revisions for both of these trials are, of course, available on CTSU.org and are linked from SWOG.org’s trial pages as well (S2013 is here and S1501 is here). Both trials are prime examples of the public-powered research that’s stock-in-trade for SWOG, the NCTN, and the NCORP. We need your participation to see them to completion and incorporate their eventual findings into improved patient care. Thank you!