Quantum Leap Healthcare Collaborative

SURMOUNT Substudy

Widely hailed as the future of phase II drug development, the adaptive I-SPY2 platform trial has set a new benchmark for efficiency, through innovation in trial design and clinical operations.

SURMOUNT (Surveillance Markers of Utility for Recurrence after Neoadjuvant Therapy for Breast Cancer) is a nested multi-center, prospective cohort study within the I-SPY2 Trial for women undergoing neoadjuvant chemotherapy for primary breast cancer, who are also undergoing definitive surgical resection and have clinical or radiographic evidence of residual tumor at the completion of chemotherapy.

Objectives:

To determine the frequency, molecular features and prognostic significance of bone marrow and circulating tumor biomarkers in participants with clinical or radiologic residual disease at the completion of neoadjuvant chemotherapy in the I-SPY 2 TRIAL.

Enrollment Criteria:

Eligible participants drawn from the population of I-SPY 2 TRIAL participants with breast cancer undergoing neoadjuvant chemotherapy at study sites who meet the following eligibility criteria:

  • Enrollment on the treatment phase of the I-SPY 2 TRIAL
  • Completed a standard neoadjuvant chemotherapy regimen or assigned treatment on I-SPY 2 and planning definitive surgical resection. Participants who have discontinued assigned treatment on I-SPY 2, switched to standard of care, and have completed a  standard neoadjuvant chemotherapy regimen are still considered eligible.
  • Pre-surgical imaging or clinical examination demonstrating residual disease in the breast.  Participants with any extent of enhancement attributable to tumor on the pre-surgical MRI are eligible. No minimum extent of palpable tumor pre-surgery is required.
  • Willing to undergo bone marrow aspiration and blood specimen collection per protocol specifications
  • No clinical evidence of distant metastatic disease. Pre-chemotherapy staging scans are sufficient in the absence of any symptoms or subsequent clinical evidence suggesting distant metastases
  • Age 18 or over and are able to give informed consent
Number of Participants:

The target number of study participants is 250.

Study Duration:

Participants will be on the study for 10 years or until recurrence, whichever comes first.The study enrollment is planned for three years

Study Sites:

Clinical sites participating in I-SPY2

Planned Analyses:

Aim 1: Estimate and compare the CTC and DTC detection rates by RCB score, tumor subtype and pCR status. Exploratory logistic regression modeling will be performed to determine what additional factors may predict DTC/CTC/CTM detection.

Aim 2:  Characterize the molecular and genetic features of DTCs, CTCs, CTMs and compare to the residual and primary tumor. We will estimate correlation coefficients for various features between cells of different types (e.g., DTCs and primary tumor) within the same participant.

Aim 3: Estimate 3-year relapse-free survival in participants with and without detection of DTCs/CTCs at surgery.  We will also explore Cox regression models using DTC/CTC detection as a predictor, first in a univariate model and then in multivariate models that include other known prognostic factors. We recognize that power is limited in this cohort to detect anything but quite large effects; these analyses are thus considered exploratory and will provide important preliminary estimates for future study design and hypothesis generation.

Registration:

clinicaltrials.gov ref: NCT02830282