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T-DM1 and Tucatinib Compared with T-DM1 Alone in Preventing Relapses in People with High Risk HER2-Positive Breast Cancer, the CompassHER2 RD Trial


Active: Yes
Cancer Type: Breast Cancer NCT ID: NCT04457596
Trial Phases: Phase III Protocol IDs: A011801 (primary)
A011801
NCI-2020-03770
Eligibility: 18 Years and older, Male and Female Study Type: Treatment
Study Sponsor: Alliance for Clinical Trials in Oncology
NCI Full Details: http://clinicaltrials.gov/show/NCT04457596

Summary

This phase III trial compares the effect of usual treatment with trastuzumab emtansine (T-DM1) alone vs. T-DM1 in combination with tucatinib. T-DM1 is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called DM1. Trastuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors, and delivers DM1 to kill them. Tucatinib blocks HER2, which may help keep cancer cells from growing and may kill them. Giving T-DM1 in combination with tucatinib may work better in preventing breast cancer from relapsing in patients with HER2 positive breast cancer compared to T-DM1 alone.

Objectives

PRIMARY OBJECTIVE:
I. To determine if the invasive disease-free survival (iDFS) with T-DM1 and tucatinib is superior to the iDFS in the control arm (T-DM1 + placebo) when administered to high risk patients with HER2-positive breast cancer and residual disease after neoadjuvant HER2-directed therapy.

SECONDARY OBJECTIVES:
I. To evaluate whether treatment with tucatinib plus T-DM1 compared to treatment with T-DM1 alone (T-DM1 plus placebo) improves the following:
Ia. Overall survival (OS).
Ib. Breast cancer free survival (BCFS).
Ic. Distant recurrence-free survival (DRFS).
Id. Disease-free survival (DFS).
Ie. Brain metastases-free survival (BMFS).
II. To evaluate whether treatment with tucatinib plus T-DM1 compared to treatment with T-DM1 alone (T-DM1 plus placebo) reduces the incidence of brain metastases.

SECONDARY CORRELATIVE OBJECTIVES:
I. To evaluate the association of tumor infiltrating lymphocyte (TIL) levels in both the primary tumor and the residual disease specimen with iDFS.
II. To determine whether there is evidence of differential treatment benefit of T-DM1 and tucatinib compared to T-DM1 and placebo in high TIL cancers compared to low TIL cancers (assessed in both the pre-neoadjuvant tumor tissue and the residual cancer tissue).
III. To evaluate the association between iDFS and the presence of detectable circulating tumor cells (CTC) at baseline, at completion of study therapy and/or 1 year after completion of study therapy.
IV. To determine the difference in absolute magnitude of benefit of tucatinib (in terms of iDFS) in the subgroup of patients with detectable CTC at baseline and the subgroup of patients without detectable CTC at baseline.

LOCAL REGIONAL EXPLORATORY OBJECTIVES:
I. To determine local regional recurrence following breast conservation based on margin width (no ink on tumor, close, > 2 mm).
II. To determine local regional recurrence following breast conservation with or without boost.
III. To compare regional recurrence based on axillary surgery –sentinel lymph node biopsy (SLNB) vs. axillary lymph node dissection (ALND) – among patients with residual nodal disease.

PATIENT-REPORTED OUTCOMES:
I. To compare quality of life (QOL) after approximately 8 cycles of the study as assessed by the Functional Assessment of Cancer Therapy (FACT)-Breast Cancer (B) Trial Outcome Index between patients randomized to T-DM1 + tucatinib or T-DM1 + placebo. (Primary Objective)
II. To compare QOL after approximately 13 cycles of the study as assessed by the FACT-B Trial Outcome Index between patients randomized to T-DM1 + tucatinib or T-DM1 + placebo. (Secondary Objective)
III. To compare various QOL domains after approximately 8 and 13 cycles of the study as assessed by the 5 subscales of the FACT-B questionnaire between patients randomized to T-DM1 + tucatinib or T-DM1 + placebo. (Exploratory Objective)
IV. To compare self-reported patient adherence and reasons for non-adherence after 1, 4, 8, and 13 cycles of the study as assessed by the Voils instrument (Domains of Subjective Extent of Nonadherence [DOSE-Nonadherence]) between patients randomized to T-DM1 + tucatinib or T-DM1 + placebo. (Exploratory Objective)
V. To compare self-reported symptomatic adverse events after 1, 4, 8, and 13 cycles of the study assessed by the Patient-Reported Outcomes (PRO) - Common Terminology Criteria for Adverse Events (CTCAE) between patients randomized to T-DM1 + tucatinib or T-DM1 + placebo. (Exploratory Objective)

TO-BE-DETERMINED CORRELATIVE OBJECTIVES:
I. To evaluate the association of circulating tumor deoxyribonucleic acid (ctDNA) tumor-specific mutations (at baseline and after completion of adjuvant HER2-directed therapy) with iDFS.
II. To evaluate the association of breast cancer intrinsic subtype and other transcriptional signatures in both the primary tumor and the residual disease specimen with iDFS.

PHARMACOKINETIC OBJECTIVES:
I. To characterize the pharmacokinetic (PK) of T-DM1 in all patients.
II. To characterize the PK of tucatinib in tucatinib-treated patients.
III. To investigate exposure–effect (efficacy and safety) relationships in tucatinib-treated patients.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive T-DM1 intravenously (IV) over 30-90 minutes on day 1 and placebo orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.

ARM II: Patients receive T-DM1 IV over 30-90 minutes on day 1 and tucatinib PO BID on days 1-21. Treatment repeats every 21 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days, then every 6 months for 10 years.

Treatment Sites in Georgia

City of Hope Atlanta
600 Celebrate Life Parkway
Newnan, GA 30265
770-400-6169
www.cityofhope.org/locations/atlanta/atlanta-cancer-center



Nancy N. and J.C. Lewis Cancer Research Pavilion at St. Joseph Candler
225 Candler Drive
Savannah, GA 31405
912-819-5778
www.sjchs.org



Northside Hospital Cancer Institute
1000 Johnson Ferry Road NE
Atlanta, GA 30342
404-303-3355
www.northside.com



Phoebe Cancer Center at Phoebe Putney Memorial Hospital
425 Third Avenue
Albany, GA 31702
229-312-5091
www.phoebehealth.com



University Cancer and Blood Center, LLC - Athens Medical Oncology
3320 Old Jefferson Road
Building 800
Athens, GA 30607
www.universitycancer.com

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.