Quantum Leap Healthcare Collaborative

QoL 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.

The Quality of Life sub-study is a prospective cohort study within the I-SPY 2 TRIAL opened on January 16 th , 2012. Our PRO sub-study aims to investigate quality of life longitudinally and explore how patient and tumor characteristics, exposure to investigational therapies, and surgical outcome impact quality of life (QOL).

Principal Investigator

Michelle Melisko, MD

Objectives

Primary Aim

To evaluate QOL based on changes in the EORTC QLQ 30 and EORTC BR23 longitudinally from before surgery and through two years post operatively in participants receiving neoadjuvant chemotherapy, biological therapies, and/or other treatments for LABC. We will analyze the following as predictors of changes in QOL:

  • MammaPrint results: high- vs. low-risk MammaPrint profile
  • Breast conserving surgery vs. mastectomy
  • Receipt of standard chemotherapy and or/hormonal therapy vs. standard chemotherapy and/or hormonal therapy and a novel agent
  • RCB: pCR and minimal residual disease (RCB 0 or 1) vs. significant residual disease (RCB 2 or 3)
  • Receipt of hormonal therapy after surgery
Secondary Aims

To evaluate changes in distress using the DT longitudinally from before surgery and through two years post operatively in participants receiving neoadjuvant chemotherapy, biological therapies, and/or other treatments for locally advanced breast cancer. We will analyze the following as predictors of changes in distress:

  • MammaPrint results: high- vs. low-risk MammaPrint profile
  • Breast conserving surgery vs. mastectomy
  • Receipt of standard chemotherapy and/or hormonal therapy vs. standard chemotherapy and/or hormonal therapy and a novel agent‍
  • RCB: pCR and minimal residual disease (RCB 0 or 1) vs. significant residual disease (RCB 2 or 3)‍
  • Receipt of hormonal therapy after surgery

To evaluate fear of recurrence longitudinally from before surgery and up through two years post-operatively using a validated five-item Fear of Recurrence scale in participants receiving neoadjuvant chemotherapy, biological therapies, and/or other treatments for LABC. We will analyze the following as predictors of Fear of Recurrence:

  • MammaPrint results: high vs. low risk MammaPrint profile‍
  • BCS vs. mastectomy‍
  • Receipt of standard chemotherapy and/or hormonal therapy vs. standard chemotherapy and/or hormonal therapy and a novel agent‍
  • RCB: pCR and minimal residual disease (RCB 0 or 1) vs. significant residual disease (RCB 2 or 3)‍
  • Receipt of hormonal therapy after surgery
Exploratory Aim

To compare QOL scores between the EORTC QLQ30 and BR23 and the PROMIS items in categories where there is some overlap of content including physical function, anxiety,depression, sexual function, and cognitive function.

Enrollment Criteria

All participants screened for I-SPY 2 will be asked to complete baseline QOL questionnaires after they have signed the screening consent. At the time of enrollment into the trial when they are assigned a treatment group, participants will receive a packet of dated questionnaires for completion at various time points. Participants who are found to be ineligible for the study based on having a tumor with a MammaPrint low-risk profile will also be invited to participate in ongoing QOL questionnaires.

Number of Participants

The study will continue to accrual with the main I-SPY 2 TRIALs.

Study Duration

Participants will be on the study for 2 years after surgery.

Study Sites

Clinical sites participating in I-SPY 2

Planned Analyses

Primary Endpoint: EORTC QLQ-C30 and EORTC BR23

Data from these instruments will be standardized to scales of 0–100 for each function and symptom using methods described in the EORTC Scoring Manual. Mean scores (and their 95% confidence intervals) for each function and each symptom will be plotted against time for the different participant subgroups (e.g., high-vs. low-risk MammaPrint profile). Statistical comparisons between different groups will be made using mixed effect models, linear if the plots look linear and nonlinear if the plots show nonlinear scores over time. Models will have fixed effects for subgroup and time with random effects for participant and random error. We will also test whether covariates such as age and tumor characteristics (e.g., size and grade) act as significant modifiers of score results. These comparisons will be carried out in R using the nlme program that can model either linear or nonlinear functions over time.

Secondary Endpoints: DT and Fear of Recurrence Scale

Mean and median scores for each participant subgroup will be plotted against time since treatment initiation. Mixed effect models will be used to test for differences between subgroups.

PROMIS

Results for questions from PROMIS will be correlated with those from the EORTC function and symptom scales. We will also examine differences between participant subgroups using PROMIS questions and compare them with differences using QLQ-C30 and BR23 using effect size to determine whether one is more sensitive than the other in detecting differences over time.