Sacituzumab Govitecan in Primary HER2-negative Breast Cancer (NCT04595565) | Clinical Trial Compass
Active — Not RecruitingPhase 3
Sacituzumab Govitecan in Primary HER2-negative Breast Cancer
Austria1,332 participantsStarted 2020-10-28
Plain-language summary
Phase III, prospective, multi-center, randomized, open label, parallel group, study in patients with HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy with 1:1 allocation to:
* Arm A: Sacituzumab govitecan (days 1, 8 q3w for eight cycles);
* Arm B: treatment of physician´s choice (TPC, defined as capecitabine or platinum-based chemotherapy for eight cycles or observation.
Treatment in either arm will be given for eight cycles.
In patients with HR-positive breast cancer, endocrine-based therapy, which includes the use of CDK4/6 inhibitors, will be administered according to local guidelines. The start of endocrine therapy will be at the discretion of the investigator; however, it will be encouraged to start after surgery/radiotherapy in patients without additional cytotoxic agents.
Adjuvant pembrolizumab can be given until the completion of radiotherapy before randomization. Within the study the use of pembrolizumab in patients with TNBC who received pembrolizumab as neoadjuvant therapy is allowed as monotherapy in the TPC arm, according to the approval of pembrolizumab in this setting.
Who can participate
Age range18 Years – 99 Years
SexALL
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Inclusion criteria
✓. Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
✓. Age at diagnosis at least 18 years.
✓. Willingness and ability to provide archived formalin fixed paraffin embedded tissue (FFPE) block from surgery after neoadjuvant chemotherapy and from core biopsy before start of neoadjuvant chemotherapy, which will be used for centralized prospective confirmation of HR status, HER2 status, Ki-67 and tumor-infiltrating lymphocytes (TILs) and for retrospective exploratory correlation between genes, proteins, and mRNAs relevant to sensitivity/resistance to the investigational agents. For patients with bilateral carcinoma, FFPE blocks from both sides have to be provided for central testing.
✓. Histologically confirmed unilateral or bilateral primary invasive carcinoma of the breast, confirmed histologically by core biopsy. The lead tumor has to be defined by the investigator based on the inclusion criteria for the respective subtype and on the risk status.
✓. Centrally confirmed HER2-negative (IHC score 0-1 or FISH negative according to ASCO/CAP guideline) and either
✓. Patients with residual invasive disease after neoadjuvant chemotherapy at high risk of recurrence defined by either:
✓
What they're measuring
1
Invasive disease free survival (iDFS) between patients treated with sacituzumab govitecan vs. treatment of physician's choice.
Timeframe: Assuming 3.25 years of recruitment with 12 months ramp-up and 42 patients per month at peak and 3 years of follow-up after the last patient in, 396 events will be needed and final analysis is expected 75 months after study start.
. Adequate surgical treatment including resection of clinically evident disease and ipsilateral axillary lymph node dissection. SNB before NACT is discouraged. Axillary dissection before NACT is not permitted. Axillary dissection, including Targeted Axillary Dissection (TAD) should be performed according to guidelines. Histologic complete resection (R0) of all invasive and in situ tumors is required.
✓. Patients must have received neoadjuvant taxane-based chemotherapy for 16 weeks (anthracyclines are permitted). This period must include 6 weeks of a taxane containing neoadjuvant chemotherapy (exception: for patients with progressive disease that occurred after at least 6 weeks of taxane-containing neoadjuvant chemotherapy, a total treatment period of less than 16 weeks is also eligible).
Exclusion criteria
✕0. In case of local progression during neoadjuvant therapy, distant metastases must be excluded by adequate imaging (CT/MRI recommend) prior to entering the trial.
✕1. Immune checkpoint inhibitor / immunotherapy during (neo)adjuvant therapy is allowed until the completion of radiotherapy.
✕2. Patients with known gBRCA1/2 mutation without indication to adjuvant olaparib therapy are allowed to participate in the trial.
✕3. An interval of less than 16 weeks since the date of final surgery or less than 10 weeks from completing radiotherapy (whichever occurs last) and the date of randomization is required.
✕4. Radiotherapy should be delivered before the start of study treatment. Radiotherapy to the breast is indicated in all patients with breast conserving surgery and to the chest wall and lymph nodes according to local guidelines as well as in all patients with cT3/4 or ypN+ disease treated by mastectomy.
✕5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
✕6. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedure or radiotherapy to NCI CTCAE v 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patients at the investigator´s discretion).
✕7. Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer.