An open-label randomized, multicenter, phase II study on neoadjuvant treatment  with trastuzumab plus docetaxel versus trastuzumab plus docetaxel plus bevacizumab according to positron emission tomography (PET) value modification in patients with early stage HER2-positive breast cancer (AVATAXHER): Design description.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS646-TPS646 ◽  
Author(s):  
Alexandre Cochet ◽  
Khaldoun Kerrou ◽  
Jean-Marc A. Nabholtz ◽  
Florent Cachin ◽  
Jean-Yves Pierga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Fdg Pet ◽  
Neoadjuvant Treatment ◽  
High Rate ◽  
Emission Tomography ◽  
Open Label ◽  
Post Surgery ◽  
Her2 Breast Cancer

TPS646 Background: For patients with early HER2+ breast cancer at diagnosis, addition of trastuzumab (T) to 6 cycles of preoperative docetaxel (D) can reach a pathological complete response (pCR) in ~50% of cases, and a high rate of conservative surgery. pCR can be predicted by changes of Fluorodeoxyglucose (FDG) tumor uptake evaluated by Positon Emission Tomography (PET) after one cycle of therapy. In order to increase this pCR rate, adding an antiangiogenic compound could be considered. Pre-clinical and phase I-II data support that the combination of bevacizumab (B) and T is synergistic and safe when patients are chemotherapy naïve. The neoadjuvant AVATAXHER trial (EUDRACT 2009-013410-26) investigates the potential increase of pCR rate by combining B with T and D for patients with HER2+ breast cancer who are not predicted for pCR by FDG PET. Methods: In this multicenter, open-label, phase II trial, 2 phases are planned after a selection period: phase I: all patients receive two cycles of therapy combining T (8 mg/kg at the first cycle, then 6 mg/kg) and D (100 mg/m2). FDG PET is also performed within 7 days before cycle 1 (baseline) and less than 3 days before cycle 2 in order to calculate changes of the tumor FDG uptake between baseline and after cycle 1 (ΔSUV). Phase 2: if ΔSUV≥70%, patients will continue to receive T and D for (cycles 3 to 6: D 100 mg/m2 + T 6 mg/kg); if ΔSUV<70%, patients are randomized 2:1 to arm A (cycles 3 to 6 D 100 mg/m2 + T 6 mg/kg + B 15 mg/kg) or arm B ( cycles 3 to 6: D 100 mg/m2 + T 6 mg/kg). The primary endpoint is pCR rate evaluated post-surgery 4 to 6 weeks after the last treatment of cycle 6. Enrolment began in May 2010 and 125 patients were to be recruited in 26 sites. According to the hypothesis that 60% of patients will have a ΔSUV<70%, it is presumed that 72 patients will be randomized. There are currently 107 patients included (as of 06 January 2012 ), 95 of them reached the phase 1; 52 of them (55%) showed a ΔSUV<70% and after randomization 34 were included in arm A and 18 in arm B.

scholarly journals Phase II study of metronomic treatment with daily oral vinorelbine as first-line chemotherapy in patients with advanced/metastatic HR+/HER2− breast cancer resistant to endocrine therapy: VinoMetro—AGO-B-046

2021 ◽  
Author(s):  
Slavomir Krajnak ◽  
Thomas Decker ◽  
Lukas Schollenberger ◽  
Christian Rosé ◽  
Christian Ruckes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Oral Vinorelbine ◽  
Her2 Breast Cancer ◽  
Line Chemotherapy

Abstract Purpose Metronomic chemotherapy (MCT) is an increasingly used treatment option in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced/metastatic breast cancer (MBC) after failure of endocrine-based therapies. Methods VinoMetro was a multicentre, open-label, single-arm, phase II study of metronomic oral vinorelbine (VRL; 30 mg/day) as a first-line chemotherapy (CT) in patients with HR+/HER2− MBC after endocrine failure. The primary endpoint was the clinical benefit rate (CBR) at 24 weeks. Results Between January 2017 and April 2019, nine patients were enrolled. The CBR was 22.2% (90% confidence interval [CI] 4.1–55.0), p = 0.211. The median progression-free survival (PFS) was 12.0 weeks (95% CI 11.3–12.7). Grade 3–4 adverse events (AEs) occurred in 22.2% of patients. One patient died of febrile neutropenia. Conclusion VinoMetro (AGO-B-046) was closed early after nine patients and occurrence of one grade 5 toxicity in agreement with the lead institutional review board (IRB). Metronomic dosing of oral VRL in HR+/HER2− MBC as first-line CT after failure of endocrine therapies showed only limited benefit in this population. Trial registration number and date of registration ClinicalTrials.gov Identifier: NCT03007992; December 15, 2016.

Neoadjuvant bevacizumab (B) and trastuzumab (T) in combination with weekly paclitaxel (P) as neoadjuvant treatment in HER2-positive breast cancer: Results from a phase II trial (AVANTHER).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 602-602
Author(s):  
Maria Fernandez Abad ◽  
Isabel Calvo ◽  
Noelia Martinez ◽  
Mercedes Herrero ◽  
Yolanda Quijano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
High Rate ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Combination Methods ◽  
Positive Breast Cancer

602 Background: B in combination with T has showed meaningful activity in patients (pts) with metastatic HER2-positive breast cancer. AVANTHER is a Phase II trial of preoperative systemic therapy combining B with T and P in a weekly regimen in HER2 positive breast cancer to assess safety and efficacy of the combination. Methods: Pts with centrally-confirmed HER2-positive (IHC 3+ or FISH positive) breast cancer (stage II or III including locally advanced) received neoadjuvant chemotherapy (NC) with weekly P (80mg/m2/week) for 12 weeks in combination with weekly T (4mg/kg loading dose and 2 mg/kg maintenance) and B (15mg/kg every 3 weeks) for 4 cycles. After surgery all pts received T (1 year) and liposomal doxorubicin plus cyclophosphamide every 3 weeks (4 cycles); primary endpoint was rate of pathological complete response (pCR) in breast and axilla. For all patients, a tissue sample at baseline as well as at surgery was collected for biomarker analyses. Results: A total of 44 pts have been enrolled. Median tumor size: 3.9 cm. Seven (19.4%) pts had stage IIA; 17 (47.2%) stage IIB; 8 (22.2%) stage IIIA and 4 (11.1%) stage IIIB. Twenty-one (58.3%) pts had both positive-hormonal receptors and 10 (27.8%) were hormone receptor negative. Eight (22.2%) pts had sentinel biopsy before NC, being negative in 6 (16.7%) cases. Data from surgery (only from 36 pts): pCR was achieved in 16 (44.4%) pts. Safety and tolerability were good, with rare adverse events of grade ≥3 [1 (2.8%) episode of severe hypertension]. Conclusions: These data show that the combination of P with T and B without an anthracycline for 12 weeks is very effective as NC in HER2 positive breast cancer pts with a high rate of pCR and minimal side effects.

Phase I/II study of neoadjuvant carboplatin, eribulin mesylate, and trastuzumab (ECH) for operable HER2 positive (HER2+) breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS659-TPS659
Author(s):  
Lee Steven Schwartzberg ◽  
Kurt W. Tauer ◽  
Robert C. Hermann ◽  
Petros G. Nikolinakos ◽  
Arthur C. Houts
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Eribulin Mesylate ◽  
Her2 Breast Cancer ◽  
Level 1

TPS659 Background: Carboplatin, docetaxel and trastuzumab (TCH) regimen yields substantial pathologic complete response (pCR) in operable HER2+ breast cancer. Eribulin mesylate (E) is a tubulin inhibitor recently shown to improve overall survival compared to taxanes and other agents in heavily pretreated metastatic breast cancer patients. This trial was designed to determine the maximum tolerated dose (MTD) of E in combination with CH (Phase I) and to determine efficacy and safety of the ECH regimen (Phase II) given as neoadjuvant therapy to early stage HER2+ breast cancer with pathologic complete response the primary endpoint. Methods: This is a multicenter prospective open label single arm trial. Eligible patients were operable stage IIA – IIIB HER2+ breast cancer, ECOG 0-1, normal LVEF, QTc < 480 msec, < grade 1 neuropathy and no history of invasive cancer within the past 3 years. Phase I planned up to 12 patients from 4 centers to 1 of 3 E dose cohorts, with pts treated at the MTD also evaluable for Phase II. Starting dose level 0 was 1.1 mg/m2 with escalation to dose level +1 at 1.4 mg/m2 and de-escalation to dose level -1 at 0.9 mg/m2 if necessary. ECH was given IV for six 3-week cycles with E d1 and d8; C AUC 6 d1; and H 8 mg/kg loading dose d1C1 and 6 mg/kg d1C2-C6. H is scheduled to continue after surgery to complete 1 year of treatment. C1 dose limiting toxicities (DLTs) were defined as: grade 4 thrombocytopenia, anemia, or neutropenia lasting > 5 days; any grade 3-4 non-hematologic toxicity attributable to E, C, H, or the combination; inability to deliver all three agents at assigned dose and schedule. Standard 3+3 dose escalation design was used. At present, 6 patients have been enrolled at dose 0 and 6 have been enrolled at dose +1. The MTD for E has not yet been determined. Phase II has planned enrollment of 44 additional patients from 8 centers with primary endpoint rate of pCR at surgery to be performed 4-8 weeks after completion of ECH and secondary endpoints of safety to include peripheral neuropathy and cardiac toxicity at treatment completion and 1 year follow up. Clinical trial information: NCT101388647.

scholarly journals Phase II Study of Metronomic Treatment With Daily Oral Vinorelbine as First-line Chemotherapy in Patients With Advanced/metastatic HR+/HER2- Breast Cancer Resistant to Endocrine Therapy: VinoMetro – AGO-B-046

2021 ◽  
Author(s):  
Slavomir Krajnak ◽  
Thomas Decker ◽  
Lukas Schollenberger ◽  
Christian Rosé ◽  
Christian Ruckes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Oral Vinorelbine ◽  
Her2 Breast Cancer ◽  
Line Chemotherapy

Abstract PurposeMetronomic chemotherapy (MCT) is an increasingly used treatment option in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (MBC) after failure of endocrine-based therapies. MethodsVinoMetro was a multicentre, open-label, single-arm, phase II study of metronomic oral vinorelbine (VRL; 30 mg/day) as a first-line chemotherapy (CT) in patients with HR+/HER2- MBC after endocrine failure. The primary endpoint was the clinical benefit rate (CBR) at 24 weeks. ResultsBetween January 2017 and April 2019, 9 patients were enrolled. The CBR was 22.2% (90% confidence interval [CI] 4.1–55.0), p=0.211. The median progression-free survival (PFS) was 12.0 weeks (95% CI 11.3–12.7). Grade 3-4 adverse events (AEs) occurred in 22.2% of patients. One patient died of febrile neutropenia.ConclusionVinoMetro (AGO-B-046) was closed early after 9 patients and occurrence of one grade 5 toxicity in agreement with the lead institutional review board (IRB). Metronomic dosing of oral VRL in HR+/HER2- MBC as first-line CT after failure of endocrine therapies showed only limited benefit in this population.Trial registration number and date of registrationClinicalTrials.gov Identifier: NCT03007992; December 15, 2016

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