COMPASSHER2 RESIDUAL DISEASE (RD), A DOUBLE-BLINDED, PHASE III RANDOMIZED TRIAL OF T-DM1 AND PLACEBO COMPARED WITH T-DM1 AND TUCATINIB
Alliance A011801: THE COMPASSHER2 TRIALS (COMPREHENSIVE USE OF PATHOLOGIC RESPONSE ASSESSMENT TO OPTIMIZE THERAPY IN HER2-POSITIVE BREAST CANCER): COMPASSHER2 RESIDUAL DISEASE (RD), A DOUBLE-BLINDED, PHASE III RANDOMIZED TRIAL OF T-DM1 AND PLACEBO COMPARED WITH T-DM1 AND TUCATINIB
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Clinical Trial Information
Trial Contact: Durand, Jennifer; Ribacchi, Stephanie
Trial Phone: 321.843.2026 ; 321-841-1077
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IRB No: C21.059.04
Protocol Abbrev: Alliance A011801
Principal Investigator: Nikita Chandrakant Shah, MD
Phase: Drug: Phase III
Age Group: Adult
Secondary Protocol No: Alliance A011801
Treatment: Arm 1: (trastuzumab emtansine, placebo) Arm 2: (trastuzumab emtansine, tucatinib)
Therapies Involved: Medication
ClinicalTrials.gov ID: NCT04457596
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Objective
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. Breast cancer free survival (BCFS). Ib. Distant recurrence-free survival (DRFS). Ic. Brain metastases-free survival (BMFS). Id. Overall survival (OS). 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.
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.
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.
After completion of study treatment, patients are followed up at 30 days, then every 6 months for 10 years. -
Key Eligibility
-Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects.Therefore, for women of childbearing potential only, a negative serum pregnancy test done ≤ 7 days prior to registration is required.
-Age ≥ 18 years (male or female)
- ECOG Performance Status 0-1
-Adequate hepatic, renal, and bone marrow function
-HER2-positive status will be based on pretreatment biopsy material and defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) according to current ASCO/CAP guidelines. Central testing is not required.
-Patients with clinical stage T1-4, N0-3 disease at presentation and residual invasive disease postoperatively as defined above are eligible. (Note: Patients with T1a/bN0 tumors are not eligible).
-Patients with residual HR-negative, HER2+ disease in the breast and/or lymph nodes per the surgical pathology report are eligible; however, patients with HR+ HER2+ cancers must have node-positive residual disease per the surgical pathology
-Patients with synchronous bilateral invasive disease are eligible provided both lesions were confirmed to be HER2-positive, and at least one of the lesions meets the criteria outlined above. Multifocal disease is allowed, as long as the largest biopsied
breast tumor was HER2-positive.