NSABP B-59/GBG 96-GeparDouze: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple-negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS605-TPS605
Author(s):  
Charles E. Geyer ◽  
Sibylle Loibl ◽  
Priya Rastogi ◽  
Sabine Seiler ◽  
Joseph P. Costantino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Placebo Control Trial ◽  
Phase Iii ◽  
Placebo Control ◽  
Double Blind ◽  
Free Survival

TPS605 Background: TNBC is associated with higher percentages of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), and women with a pCR have a favorable prognosis. However, Liedtke (2008) and Loibl (2017) found that women with residual disease have a substantially higher risk of recurrence than women with other subtypes of breast cancer. Additionally, Adams (2017) and Schmid (2017) found that therapeutic blockade of PD-L1 binding by atezolizumab has resulted in relevant anti-tumor efficacy. Methods: Design: This is a phase III, double blind, placebo-control trial evaluating neoadjuvant atezolizumab with NAC followed by adjuvant atezolizumab in TNBC. Pts are stratified by region (North America; Europe), tumor size (1.1-3.0cm; >3.0cm), AC/EC schedule (q2w; q3w), nodal status (positive; negative), and PD-L1 status (positive; negative or indeterminate) then randomized 1:1 to receive atezolizumab/placebo 1200 mg IV every 3 wks concurrently with both sequential regimens of weekly paclitaxel 80 mg/m2 IV for 12 doses with every 3-wk carboplatin AUC of 5 IV for 4 doses followed by AC/EC every 2-3 wks (per investigator discretion) for 4 cycles. Following surgery, pts resume atezolizumab/placebo 1200 mg IV every 3 wks as adjuvant therapy for 6 months. Radiotherapy based on local standards is co-administered with atezolizumab/placebo. Eligibility criteria: Centrally confirmed ER-neg, PR-neg, HER2-neg invasive breast cancer by ASCO/CAP guidelines. Primary tumor must be stage T2 or T3 if cN0 or cN1 with negative biopsy or T1c, T2, or T3 if cN1 with positive biopsy or cN2 or cN3. LVEF >55% and no significant cardiac history. Statistical methods: Co-primary endpoints are event-free survival (EFS) and pCR breast/nodes. Secondary endpoints include pCR breast, overall survival, distant disease-free survival, safety and toxicity. Trial is an academic collaboration between NSABP and GBG with support from Genentech/Roche. Support: Genentech/Roche. Clinical trial information: NCT03281954.

A randomized, triple negative breast cancer enrolling trial to confirm molecular profiling improves survival (ARTEMIS).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS590-TPS590 ◽  
Author(s):  
Clinton Yam ◽  
Kenneth R. Hess ◽  
Jennifer Keating Litton ◽  
Wei Tse Yang ◽  
Helen Piwnica-Worms ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Triple Negative Breast Cancer ◽  
Primary Tumor ◽  
Triple Negative ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Type I ◽  
Free Survival

TPS590 Background: Following neoadjuvant chemotherapy (NACT), patients (pts) with triple negative breast cancer (TNBC) achieving pathologic complete response/residual cancer burden-0 (pCR/RCB-0) or minimal residual disease (RCB-I) have an improved relapse free survival when compared to pts with more extensive residual disease (RCB-II/III) (Symmans et al, JCO 2017). Pts with chemo-resistant TNBC have a poor prognosis as there are currently no FDA-approved targeted agents available for TNBC. We previously reported the ability of a novel gene expression signature (GES) to predict sensitivity to NACT (Hatzis et al, JAMA 2011). Here we seek to prospectively validate the use of this GES in combination with imaging to predict response to NACT and establish the clinical impact of selecting pts predicted to have non-responsive disease (NRD) for enrollment in clinical trials of targeted therapy. Methods: All pts will undergo a biopsy of the primary tumor for molecular characterization (MC) and will be randomized 2:1 to know their MC results (intervention arm) or not (control arm). A maximum of 360 pts will be enrolled and randomized using a group sequential design with one-sided O’Brien-Fleming boundaries, with two equally spaced binding interim tests for futility and superiority and one final test, having an overall Type I error of 0.05 and power of 0.80 to detect an improvement in pCR/RCB-I from 50% to 64%. Secondary endpoints include rates of clinical trial enrollment, disease free survival and integrated biomarker analyses. All pts will receive 4 cycles of anthracycline-based NACT with imaging done every 2 cycles to assess response. After completion or progression on anthracycline-based NACT, pts predicted to have NRD based on MC/imaging (intervention arm) or imaging alone (control arm) will be offered enrollment on a clinical trial. Pts are eligible if they have stage I-III TNBC with a primary tumor that is ≥1.5cm. Pts with contraindications to anthracyclines and/or taxanes are excluded. Enrollment began in November 2015. 105 pts have been enrolled to date with 71 and 34 pts randomized to the intervention and control arms, respectively. Clinical trial information: NCT02276443.

The Preventive Effects of Boron-Based Gel on Radiation Dermatitis in Patients Being Treated for Breast Cancer: A Phase III Randomized, Double-Blind, Placebo-Controlled Clinical Trial

2022 ◽  
pp. 1-8
Author(s):  
Fikrettin Sahin ◽  
Mohammad Bagher Pirouzpanah ◽  
Hossein Bijanpour ◽  
Mohammad Mohammadzadeh ◽  
Reza Eghdam Zamiri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Placebo Group ◽  
Intervention Group ◽  
Phase Iii ◽  
Radiation Dermatitis ◽  
Placebo Control ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Moist Desquamation

<b><i>Introduction:</i></b> Radiation dermatitis (RD) is a side effect of radiation therapy (RT) which is experienced by over 90% of patients being treated for breast cancer. The current clinical trial was conducted to measure the preventative effects of a boron-based gel on several different clinical outcomes (dermatitis, erythema, dry desquamation, and moist desquamation) after 25 radiotherapy sessions. <b><i>Methods:</i></b> This research used a double-blind parallel-group design with a placebo control (<i>n</i> = 76) and randomized group (<i>n</i> = 181), with all participants being between 18 and 75 years old. Fifteen minutes before each radiotherapy, participants in the intervention group were given a gel containing 3% sodium pentaborate pentahydrate, while those in the placebo group received a gel with no chemical substance. Dermatitis, erythema, dry desquamation, and moist desquamation were compared between the 2 groups. <b><i>Results:</i></b> At baseline, there were no significant differences between the groups (<i>p</i> &#x3e; 0.05), except for body mass index. After 14 days of treatment, dermatitis (98.7% vs. 9.9%; <i>p</i> &#x3c; 0.001), erythema (96.1% vs. 12.2%; <i>p</i> &#x3c; 0.001), dry desquamation (50% vs. 3.9%; <i>p</i> &#x3c; 0.001), and moist desquamation (18.4% vs. 0.6%; <i>p</i> &#x3c; 0.001) were much more common in the placebo group than the intervention group. To prevent dermatitis, erythema, dry desquamation, and moist desquamation in 1 patient, on average, 1.1 (95% confidence interval [CI]: 1.1–1.2), 1.2 (95% CI: 1.1–1.3), 2.2 (95% CI: 1.7–2.9), and 5.6 (95% CI: 3.8–11.0) patients need to be treated, respectively. <b><i>Conclusion:</i></b> The boron-based gel has a significant preventive effect on several categories of RD which might be used by clinicians in breast cancer.

Randomized, phase II trial to evaluate the efficacy and safety of atezolizumab plus capecitabine adjuvant therapy compared to capecitabine monotherapy for triple receptor-negative breast cancer (TNBC) with residual invasive cancer after neoadjuvant chemotherapy (MIRINAE trial, KCSG-BR18-21).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS597-TPS597
Author(s):  
In Hae Park ◽  
Gun Min Kim ◽  
Jee Hyun Kim ◽  
Hanjo Kim ◽  
Kyong Hwa Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Phase Ii ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Free Survival ◽  
Disease Free

TPS597 Background: Triple negative breast cancer (TNBC), lack of ER, PR and HER2 expression, is known to have aggressive clinical features such as early recurrence, drug resistance, and frequent distant metastasis at the diagnosis. The most effective chemotherapy combinations used for early TNBC include anthracycline, taxanes, and/or platinum agents. Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) provides important prognostic information and is considered as a surrogate endpoint in many clinical trials especially with TNBC. Patients with residual invasive disease after NAC have a high risk for early relapse and worse prognosis compared to those with pCR. Therefore, patients who did not get pCR could be better candidates for additional adjuvant treatment because their risk of recurrence would be higher than those with pCR. The CREATE-X (capecitabine for residual cancer as adjuvant therapy) trial howed that adjuvant capecitabine treatment improved 5-yr rate of disease free survival in TNBC subtype. A recent study indicated that immunosuppressive microenvironment had developed even in early stage of TNBC with increased T cells with a high exhaustion signature which are targets of immune modulating agents. Therefore, earlier cooperation of immune modulating drugs would be beneficial by generating a long-lasting anti-tumor immune response to micrometastatic disease, thus preventing disease relapse or recurrence. Methods: This study is a phase II, multicenter, randomized open label trial of atezolizumab (anti-PD-L1 antibody) and capecitabine compared with capecitabine in patients with TNBC who had residual disease after NAC. 284 patients will be enrolled from 15 sites in Korea with a primary objective to access the 5-yr invasive disease-free survival (IDFS) rate. Secondary objectives include 5-yr IDFS rate in PD-L1 positive population, distant relapse free survival (DRFS), overall survival (OS), and safety. Major inclusion and exclusion criteria are followings; 1) histologically confirmed TNBC, 2) received anthracycline and taxane based NAC followed by complete breast surgery, 3) residual disease after NAC must be ≥1cm in the greatest dimension, and/or have macroscopically positive lymph nodes. The study is open with 13 patients enrolled at the time of submission. Clinical trial information: NCT03756298 .

Phase III postneoadjuvant study evaluating sacituzumab govitecan, an antibody drug conjugate in primary HER2-negative breast cancer patients with high relapse risk after standard neoadjuvant treatment: SASCIA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS602-TPS602
Author(s):  
Frederik Marmé ◽  
Elmar Stickeler ◽  
Jenny Furlanetto ◽  
Carsten Denkert ◽  
Marcus Schmidt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Phase Iii ◽  
Nodal Involvement ◽  
Free Survival ◽  
Risk Of Recurrence ◽  
Disease Free

TPS602 Background: Women with triple-negative breast cancer (TNBC) having residual disease after neoadjuvant chemotherapy (NACT) as well as HR-positive/HER2-negative breast cancer (BC) with a CPS (clinical and post treatment pathological stage) +EG (estrogen receptor status and grade) score ≥ 3 or score 2 and nodal involvement after NACT (ypN+) are at high risk of recurrence. Sacituzumab govitecan is approved for the treatment of patients with metastatic TNBC who received at least two prior therapies for metastatic disease and has shown activity in heavily pretreated patients with metastatic HR-positive/HER2-negative BC. Therefore, sacituzumab govitecan may represent a new option against the resistant residual disease after standard NACT. Methods: SASCIA is a phase III, prospective, international, multi-center, randomized, open label, parallel group study in patients with HER2-negative BC with residual disease after NACT (NCT04595565). Eligible patients must have received taxane-based NACT for 16 weeks, including at least 6 weeks of a taxane. Patients should be at high risk of recurrence after treatment, defined as having centrally confirmed HER2-negative BC (IHC score 0-1 or FISH negative according to ASCO/CAP guideline) assessed preferably on tissue from postneoadjuvant residual invasive disease of the breast and either HR-negative (<1% positive stained cells), with any residual invasive disease > ypT1mi after NACT or HR-positive (≥1% positive stained cells), with a CPS+EG score ≥ 3 or CPS+EG score 2 and ypN+ using local ER and grade assessed on core biopsies taken before NACT. Radiotherapy should be delivered before the start of study treatment. Patients are randomized 1:1 to receive either sacituzumab govitecan 10 mg/kg body weight (days 1, 8 q3w for eight cycles) or treatment of physician´s choice (capecitabine 2000 mg/m² day 1-14 q21 or platinum-based chemotherapy i.e. carboplatin AUC 5 q3w or AUC 1.5 weekly for eight 3 weekly cycles or observation). Randomization is stratified by HR status (HR-positive vs negative) and nodal involvement after NACT (ypN+ vs ypN0). In patients with HR-positive BC, endocrine-based therapy will be administered according to local guidelines. The primary endpoint is invasive disease-free survival (iDFS). Secondary endpoints include comparison of overall survival (OS, key secondary endpoint), distant disease-free survival, locoregional recurrences-free interval, safety, compliance, iDFS and OS according to stratified and - predefined subgroups, patient reported outcome, and quality of life between treatment arms. As of February 2 2021, 7/1200 patients have been randomized in Germany. International study groups will join soon. Clinical trial information: NCT04595565.

Alliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer

2021 ◽  
Author(s):  
Ciara C O'Sullivan ◽  
Karla V Ballman ◽  
Linda McCall ◽  
Anuhya Kommalapati ◽  
Tyler Zemla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Residual Disease ◽  
Disease Free Survival ◽  
The United States ◽  
Distant Recurrence ◽  
Primary Objective ◽  
Phase Iii ◽  
Her2 Positive ◽  
Free Survival ◽  
Disease Free

This report describes the rationale, purpose and design of A011801 (CompassHER2 RD), an ongoing prospective, multicenter, phase III randomized trial. Eligible patients in the United States (US) and Canada with high-risk (defined as ER-negative and/or node-positive) HER2-positive (HER2+) residual disease (RD) after a predefined course of neoadjuvant chemotherapy and HER2-directed treatment are randomized 1:1 to adjuvant T-DM1 and placebo, versus T-DM1 and tucatinib. Patients have also received adjuvant radiotherapy and/or endocrine therapy, if indicated per standard of care guidelines. The primary objective of the trial is to determine if the invasive disease-free survival (iDFS) with T-DM1 plus tucatinib is superior to iDFS with T-DM1 plus placebo; other outcomes of interest include overall survival (OS), breast cancer-free survival (BCFS), distant recurrence-free survival (DRFS), brain metastases-free survival (BMFS) and disease-free survival (DFS). Correlative biomarker, quality of life (QoL) and pharmacokinetic (PK) endpoints are also evaluated.

Denosumab versus placebo as adjuvant treatment for women with early-stage breast cancer at high risk of disease recurrence (D-CARE): An international, placebo-controlled, randomized, double-blind phase III clinical trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS662-TPS662
Author(s):  
Paul E. Goss ◽  
Carlos H. Barrios ◽  
Arlene Chan ◽  
Dianne M. Finkelstein ◽  
Hiroji Iwata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Bone Metastasis ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Double Blind ◽  
Free Survival ◽  
Patient Reported

TPS662 Background: In women with early-stage breast cancer, bone is a common site of distant recurrence and represents approximately 40% of all first recurrences. Preclinical studies demonstrated that inhibition of RANKL significantly delays skeletal tumor formation, reduces skeletal tumor burden, and prolongs survival of tumor-bearing mice. Denosumab is approved for the prevention of skeletal-related events (SREs) in patients with established bone metastases from solid tumors. The D-CARE trial is designed to assess if denosumab treatment prolongs bone metastasis-free survival (BMFS) and disease-free survival (DFS) in the adjuvant breast cancer setting. The primary endpoint of this event-driven trial is BMFS. Secondary endpoints include DFS and overall survival. Additional endpoints include safety, breast density, time to first on-study SRE (following the development of bone metastasis), patient reported outcomes, and biomarkers. Methods: In this international, randomized, double-blind, and placebo-controlled phase 3 trial, 4509 women with stage II or III breast cancer at high risk for recurrence and with known hormone and HERE2 receptor status were randomized. High risk was defined as biopsy evidence of breast cancer in regional lymph nodes, tumor size > 5 cm (T3), or locally advanced disease (T4). Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination, must be planned. Patients with a prior history of breast cancer (except DCIS or LCIS) or distant metastasis, oral bisphosphonate (BP) use within 1 year of randomization, or any intravenous BP use, were not eligible. Patients were randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 months, then every 3 months for a total of 5 years of treatment. Supplemental vitamin D (≥ 400 IU) and calcium (≥ 500 mg) were required. The trial, sponsored by Amgen Inc., began enrolling patients in June 2010 and completed enrollment in late 2012. Clinical trial information: NCT01077154.

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