Phase I/II study of H3B-6545, a novel selective estrogen receptor covalent antagonist (SERCA), in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1018-1018
Author(s):  
Erika P. Hamilton ◽  
Judy S. Wang ◽  
Timothy J. Pluard ◽  
Stephen R. D. Johnston ◽  
Aki Morikawa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Phase I ◽  
Phase Ii ◽  
Single Agent ◽  
Clinical Activity ◽  
Her2 Breast Cancer ◽  
Metastatic Setting ◽  
Heavily Pretreated ◽  
Esr1 Mutations

1018 Background: H3B-6545, a selective, small molecule covalent antagonist of ERα demonstrated preclinical and preliminary clinical activity against ER+ breast cancer (Hamilton EP, SABCS, 2020). This study evaluated the activity and tolerability of H3B-6545 in patients (pts) with metastatic ER+, HER2-, breast cancer refractory to endocrine therapy. Methods: Patients received H3B-6545 once daily at the recommended phase II dose of 450 mg. The primary objective of the phase II is to estimate the objective response rate (ORR), progression-free survival (PFS), clinical benefit rate (CBR) and secondary objectives include safety. Results: 83 pts were treated with 450 mg in the phase II part of the trial. Additionally, 11 pts were treated with 450 mg in the phase I part of the trial and are included in this analysis. Median age was 62 years (range: 38 to 87 years), 81% had liver and/or lung metastases, and the median number of prior therapies for metastatic disease was 3 (range: 1 to 8). Prior CDK4/6 inhibitors, aromatase inhibitors, fulvestrant, and chemotherapy were received by 85%, 80%, 72%, and 50% of the pts, respectively. 58 pts (62%) had detectable ESR1 mutations in liquid biopsies, including 10 (11%) and 19 pts (20%) who had clonal Y537S and clonal D538G mutation, respectively. As of January 29, 2021, grade (gr) 2 or higher adverse events (AE) reported in ≥10% were anemia (19%), fatigue (16%), nausea (17%), and diarrhea (12%). Laboratory gr 2 or higher abnormalities reported in ≥10% pts were creatinine clearance decrease (38%), hemoglobin decrease (37%), bilirubin increase (12%), ALT increase (14%), AST increase (13%), and creatinine increase (11%). AE of gr 1 sinus bradycardia (asymptomatic) was reported in 34% and gr 2 (symptomatic, no intervention needed) was reported in 5%. Gr 2 and 3 QTcF prolongation were reported in 2 and 3 pts, respectively. There were no treatment-related deaths. Efficacy estimates are presented in the table below. Responses were observed in heavily pretreated pts, pts with visceral metastases and in pts who received prior fulvestrant, CDK4/6 inhibitor, and/or chemotherapy in the metastatic setting. Conclusions: H3B-6545 has a manageable safety profile and demonstrated single-agent anti-tumor activity in heavily pretreated ER+, HER2- mBC patients. Clinical activity was observed in pts with ESR1 mutations. Clinical trial information: NCT03250676 .[Table: see text]

Evaluation of RAD1901, a novel investigational, selective estrogen receptor degrader (SERD), for the treatment of ER-positive (ER+) advanced breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1014-1014 ◽  
Author(s):  
Aditya Bardia ◽  
Peter Kabos ◽  
Richard Elledge ◽  
Dannie Wang ◽  
Jinshan Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Phase 1 ◽  
Single Agent ◽  
Response To Treatment ◽  
Low Grade ◽  
Her2 Breast Cancer ◽  
Metastatic Setting ◽  
Esr1 Mutations ◽  
Grade 3

1014 Background: The treatment of advanced ER+ breast cancer remains a clinical challenge with the majority of patients eventually progressing due to resistance to endocrine therapy. RAD1901 is a novel, nonsteroidal, oral SERD that has demonstrated dose dependent degradation of ER, and ER regulated genes in preclinical studies. In multiple in vivo patient derived xenograft models of breast cancer, including those harboring ESR1 mutations, RAD1901 demonstrated significant antitumor activity. Methods: In a phase-1 Study RAD1901-005 (ClinicalTrials.gov ID: NCT02338349), patients with advanced ER+ breast cancer were enrolled in dose escalation cohorts, followed by a safety expansion cohort. Key inclusion criteria include postmenopausal women aged 18 years or older, with advanced ER+, HER2- breast cancer, who have received ≤ 2 prior chemotherapy regimens in the metastatic setting and > 6 months of prior endocrine therapy. ESR1 mutation status was determined from circulating tumor DNA (ctDNA) samples. Clinical outcomes were evaluated based on RECIST v1.1 criteria. Results: As of January 25, 2017, total of 39 patients were enrolled at the 400 mg qd dose. Patients were heavily pre-treated (median lines of prior therapy = 3), with 38% and 41% having previously received fulvestrant and palbociclib/CDK4/6 inhibitor, respectively. RAD1901 was generally well-tolerated, with the most common adverse events being low grade nausea (Grade 3/4 = 0%) and dyspepsia (Grade 3/4 = 0%). ESR1 mutations, including D538G, Y537S/N/C, L536H/P/R, S436P and E380Q, were detected at baseline in 44% of patients and dynamic changes in the allele frequency of ESR1 mutations were observed in response to treatment. Confirmed partial responses were observed in patients with ESR1 mutations, and those who had previously received fulvestrant and palbociclib. Conclusions: RAD1901 has demonstrated evidence of single agent activity, with confirmed partial responses in heavily pre-treated patients with advanced ER+ breast cancer, including those with ESR1 mutations, warranting additional clinical development. Clinical trial information: NCT02338349.

Phase II Trial of Combination of the Histone Deacetylase Inhibitor ITF2357 and Meclorethamine Demonstrates Clinical Activity and Safety in Heavily Pretreated Patients with Relapsed/Refractory Hodgkin Lymphoma (HL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2586-2586 ◽  
Author(s):  
Carmelo Carlo-Stella ◽  
Anna Guidetti ◽  
Simonetta Viviani ◽  
Valeria Bonfante ◽  
Pinuccia Valagussa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Response To Therapy ◽  
Prior Treatment ◽  
Study Entry ◽  
Clinical Activity ◽  
Synergistic Activity ◽  
Heavily Pretreated ◽  
Ongoing Phase

Abstract Introduction: HL patients with refractory disease or relapsing after autologous stem cell transplantation (SCT) have very poor prognosis with currently available salvage chemotherapy. ITF2357 (Italfarmaco S.p.A., Milano, Italy) is an orally bioavailable hydroxamate inhibitor of class I and II histone deacetylases (HDACs) with preclinical and clinical activity as single agent in hematopoietic cancers. Our preclinical data demonstrating a synergistic activity of ITF2357 with the alkylating agent Meclorethamine in HL cell lines, established the rationale for this currently ongoing phase II study aimed to determine activity and safety of the sequential ITF2357 and Meclorethamine treatment. Methods: Patients with relapsed/refractory HL who have failed second- or subsequent-line salvage chemo-radiotherapy were enrolled. Eligibility criteria included prior treatment with autologous and/or allogeneic SCT, prior treatment with single agent Meclorethamine, at least one target lesion ≥2 cm, ECOG performance status of 0–1, and platelet ≥75,000/μL. ITF2357 (50 mg QID, per os, days 1–3) followed by Meclorethamine (6 mg/sqm, intravenously, day 4) was dosed in 3-week cycles until disease progression or appearance of clinical significant toxicity, but for a maximum of 12 cycles. Tumor responses were determined after cycles 2, 6, 9 and 12 by computed tomography (CT) and positron emission tomography (PET) scan. Serum levels of thymus- and activation-regulated chemokine (TARC) were assessed by ELISA prior to each cycle of therapy. Results: To date, 19 patients have been enrolled (16 males and 3 females; median age, 33 years; range, 21–61 years), including 8 patients enrolled in a preliminary compassionate use trial, and 11 patients of a planned 23 enrolled in this ongoing phase II trial. Prior to study entry, patients received a median of 5 (range 2–7) lines of treatment with autologous SCT performed in 15 (79%) and an additional allogeneic SCT in 5 (26%) patients. At study entry, 6 patients had relapsed and 13 refractory HL. Seventeen of 19 patients received a median of 3 cycles (range, 1–10) of ITF2357/Meclorethamine and are evaluable for response by CT and PET scans. Best response to therapy included 2 (12%) complete remissions (CR) and 3 (18%) partial remissions (PR), for an overall response rate (ORR) of 30%. In addition, 5 (29%) patients had stable disease (SD) with 4 (23%) patients achieving SD for ≥4 months, while 7 (41%) patients progressed. After the first cycle of therapy, serum TARC levels were decreased by 70±16% (mean±SEM, P ≤0.05) in 5 patients who achieved major clinical responses (PR+CR), and by 16±14% (P = ns) in patients who achieved SD. Overall, therapy was well tolerated without significant adverse events, and no patient required dose reductions for management of toxicities. The most common drug-related non-hematological toxicities were grade 1–2 nausea (12/17) and fatigue (14/17). Four patients experienced infections [pneumonia (n = 1), oral herpes simplex (n = 2), oral candidiasis (n = 1)]. No prolongation of QT/QTc interval has been detected over 70 therapy cycles. Hematological toxicities included grade 1–2 anemia (13/17), neutropenia (7/17), and thrombocytopenia (12/17). Grade 3–4 neutropenia and thrombocytopenia were observed in 7 and 8 patients, respectively. RBC and platelet transfusions were required by 4 and 5 patients, respectively. Conclusions: Preliminary results from this ongoing trial suggest that ITF2357, in combination with Meclorethamine, demonstrates significant anti-tumor activity in heavily pretreated relapsed/refractory HL and is well tolerated. Preliminary data also suggest that early decrease in serum TARC levels may predict response to therapy.

Combination of Sorafenib, Idarubicin, and Cytarabine Has a High Response Rate in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Younger Than 65 Years

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 768-768 ◽  
Author(s):  
Farhad Ravandi ◽  
Jorge Cortes ◽  
Stefan Faderl ◽  
Guillermo Garcia-Manero ◽  
Susan O’Brien ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Phase I ◽  
Cell Lines ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
High Response Rate ◽  
Clinical Activity ◽  
Mutation Burden

Abstract Background: Sorafenib is an orally active multi-kinase inhibitor with potent activity against the Raf/ERK/MEK pathway, VEGFR, PDGFR-β, and c-KIT. In vitro, it has growth-inhibitory effects in several AML cell lines with or without constitutive activation of ERK signaling. Sorafenib selectively induces cell growth arrest and apoptosis in FLT3-mutant human AML cell lines at nM concentrations. In a phase I study of single agent sorafenib in patients (pts) with AML escalating doses were well tolerated with no myelosuppression and with significant clinical activity predominantly (but not exclusively) in FLT3 mutated pts. Methods: This study was conducted to determine the tolerability and efficacy of combination of sorafenib with cytarabine 1.5 g/m2 iv over 24 hours daily × 4 (× 3 for pts over 60) and idarubicin 12 mg/m2 iv daily × 3. In the phase I portion of study, pts with relapsed AML were treated with escalating doses of sorafenib po (400 mg qod, 400 mg daily and 400 mg bid) for 7 days during induction, and 400 mg bid was established as a safe dose for phase II evaluation. Pts achieving CR receive up to 5 courses of consolidation with idarubicin 8 mg/m2 iv daily × 2 and cytarabine 0.75 g/m2 iv daily × 3 in addition to continuous sorafenib 400 mg po bid for up to 28 days per cycle. Maintenance with sorafenib 400 mg bid would continue for up to a year after consolidation. Results: Ten pts (median age 34 years, range 21–58) with relapsed AML (median prior therapy 2, range 1–6) were treated on the phase I portion. Seven had FLT3-ITD mutation (5 with high mutation burden, 2 with low), and 3 were negative. Four achieved CR, and 6 failed. In the phase II portion, 30 pts (including 8 with FLT3-ITD and 2 with FLT3-TKD) have been treated. Median age is 53 years (range 18 – 65) Cytogenetics were diploid in 13, +8 in 3, −5/−7 in 3, t(9;11) in 1, miscellaneous in 6, and unavailable in 4. The median presentation WBC was 4.6 × 109/L (range 1.5 –122.7 × 109/L). FLT3 mutation burden was low in blasts from 4 pts, and high in 6). Five pts were FLT3-ITD+/NPM1-. Among 25 evaluable pts, 22 (88%) have achieved CR (n=19), or CRi (n=3); 1 achieved PR, 1 died at induction from pneumonia, 1 was resistant; 5 pts are too early. The regimen is well tolerated and grade 3 adverse events thought to be possibly related to the study combination have included elevation of transaminases (3), hyperbilirubinemia (4), small bowel obstruction (1), diarrhea (2), rash (2), pericarditis (1), elevated creatinine (1), and atrial fibrillation (1). Median follow-up is 8 weeks (range, 1 – 28) with the probability of survival at 6 months of 87%; 2 pts have relapsed with CR durations of 2 and 3 months. Samples from 8 pts were studied prior to and 24–48 hours post sorafenib administration, and prior to chemotherapy. In six pts (75%), sorafenib alone induced apoptosis in peripheral blood blasts and in CD33/CD34 positive leukemia progenitor cells as determined by flow cytometry. Expression of phospho-ERK (pERK) was detectable by flow cytometry in 5 out of 7 samples tested at baseline; 24-hour exposure to sorafenib resulted in >50% downregulation of pERK in 3 of the 5 samples. Plasma inhibitory assay was performed using day 7 samples from 10 pts; mutant FLT3 was suppressed by all samples with 5-fold more potent suppression against mutant versus wildtype FLT3. Conclusions: Combination of sorafenib with idarubicin and cytarabine is safe and has a high CR rate in frontline therapy of younger pts with AML. Correlative studies confirm potent activity of sorafenib against ERK and FLT3 signaling.

Nanoparticle albumin-bound (Nab) paclitaxel (P) in combination with bevacizumab (B) with and without gemcitabine (G): Early experience at the Braman Family Breast Cancer Institute

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10748-10748
Author(s):  
C. F. Lobo ◽  
G. Lopes ◽  
O. Silva ◽  
S. Gluck
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Preliminary Evidence ◽  
Clinical Activity ◽  
Hemorrhagic Complication ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
Heavily Pretreated ◽  
Grade 3

10748 Background: Nab-P improves outcomes when compared against single agent cremophor-based P, as does the addition of bevacizumab or gemcitabine to the same agent. There are no available data regarding combinations of Nab-P with B and/or G. Ongoing investigational efforts are evaluating various doublets with these agents, but, to the best of our knowledge, not all 3 of them in the same regimen. All drugs are currently FDA-approved in the treatment of breast cancer. Methods: Review of single-institution experience, evaluating safety and preliminary evidence of activity with the use of Nab-P and B with and without G in heavily pretreated her2neu negative metastatic breast cancer patients. Assessment of response was undertaken by the investigators independently of treating physician. RECIST criteria were used. Three patients received Nab-P and B at the following doses: Nab-P 100 mg/m2, B 10 mg/kg every 2 weeks, and 2 patients received all 3 drugs as follows: Nab-P 100 mg/m2, G 1,000 mg/m2, B 10 mg/kg every 2 weeks. Results: Five women have been evaluated. Median age was 51 (range 34–69). Two patients had hormone-receptor positive disease and 3 had ER/PR/Her2neu-negative cancer. Prior number of regimens was 3 (range 2–7). Four patients had been treated with a taxane. One received both paclitaxel and docetaxel, and 3 docetaxel only. A median of 5 cycles have been administered (range 3–9). First-cycle grade 3/4 toxicity was seen in only one patient who had a baseline grade 2 thrombocytopenia that progressed to grade 3. The thrombocytopenia resolved without requiring transfusion and without any hemorrhagic complication. Another patient developed grade 2 peripheral neuropathy. Two patients are not yet assessable for response. At time of first evaluation 1 patient had progressive disease (Nab-P, B; 7 prior lines of treatment), one had stable disease (Nab-P, B, G; 3 prior lines of therapy, including docetaxel), and 1 had a partial response (Nab-P, B, G; 2 prior therapies, including docetaxel). Conclusions: These very preliminary data suggest that Nab-P in combination with B with and without G is a safe regimen and formal Phase I/II trials are being developed to confirm its clinical activity. [Table: see text]

Identification of predictive markers of clinical activity from a phase II trial of single agent pertuzumab (rhuMab 2C4), a HER dimerization inhibitor, in advanced ovarian cancer (OC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3001-3001 ◽  
Author(s):  
L. Amler ◽  
M. S. Gordon ◽  
A. Strauss ◽  
N. Rabbee ◽  
M. K. Derynck ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Ca 125 ◽  
Clinical Activity ◽  
Fresh Tissue ◽  
Formalin Fixed Paraffin ◽  
Heavily Pretreated ◽  
Dimerization Inhibitor

3001 Background: Pertuzumab (P), a humanized HER2 antibody, represents a new class of targeted agents called HER dimerization inhibitors (HDIs). P inhibits dimerization of HER2 with EGFR, HER3 and HER4, and subsequently inhibits signaling through MAP and PI3 kinases. Interim data from a phase II trial suggested that P has activity in OC, especially in a subset of tumors with activated HER2 (Abstract #5051 ASCO 2005). Methods: 123 pts with relapsed OC were treated with P. Cohort 1 was treated with 840mg followed by 420mg and cohort 2 with 1050mg every 3 weeks. Fresh tissue biopsies were mandated from Cohort 1, and archival formalin fixed paraffin tissue (FFPET ) were obtained from both cohorts. Molecular expression studies from FFPET and fresh tissue were conducted. Results: From final data of 117 evaluable pts, 5 pts had objective partial responses (RR = 4.3%). Eight pts (6.8%) had SD for ≥ 6 months, and an additional 4 pts (3.4%) had SD with CA-125 reduction of ≥50%. Overall rate of activity = 14.5%. Of the 65 fresh tumor biopsies, 28 were evaluable and 8 (28.6%) were positive for phosphorylated HER2 (pHER2) by ELISA. Among pts who had pHER2 status determined, TTP was 20.9 weeks for pHER2+ pts (n=8), compared to 5.8 weeks for pHER2- (n = 20). Data from microarray expression profiling were analyzed with respect to pHER2 status from the same tumors. The expression levels of HER2, EGFR and HER3 in combination with the expression of certain HER ligands may be predictive of pHER2 status. We have extended these analyses to qRT-PCR from macrodissected FFPET of HER receptors and ligands. This was analyzed with respect to clinical outcome. Preliminary analyses of expression data suggest that HER receptors and ligands may be promising candidates for diagnostic markers. Updated data in 78 OC pts will be presented. Conclusions: Clinical activity was observed in 14.5% of pts with heavily pretreated OC (PRs, SD ≥ 6 months, and SD with CA-125 reductions of ≥50%). This study suggests that P may be active in OC, and that specific HER receptors and ligands may be promising diagnostics for identifying tumors responsive to P. [Table: see text]

A phase II trial of trabectedin (T) in patients with hormone receptor-positive, HER2-negative advanced breast cancer, according to xeroderma pigmentosum gene (XPG) expression.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS652-TPS652
Author(s):  
Ahmad Awada ◽  
Javier Cortes ◽  
Miguel Martin ◽  
Philippe Aftimos ◽  
Mafalda Oliveira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Hormone Receptor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Open Label ◽  
Hormone Receptor Positive ◽  
Metastatic Setting

TPS652 Background: Hormone receptor-positive, HER2-negative breast cancer (BC) is currently associated with 3-4 years overall survival in the metastatic setting and, after ≥2 relapses, therapeutic approaches are reduced. XPG expression is frequently modified in BC. T is a cytotoxic agent that forms a complex with the XPG, inducing cell apoptosis. As a single agent, T has shown anti-tumor activity in patients with poor prognosis BC, and a better response to T in BC patients with XPG RNA overexpression has been observed. Methods: This is an open-label, phase II study of T (1.3 mg/m2 in 3-hour intravenous infusion every 3 weeks) in patients with hormone receptor-positive, HER2-negative advanced BC, according to their primary tumor’s XPG expression. Primary endpoint: to evaluate the efficacy of T in terms of progression free survival rate at 4 months (PFS4) according to the patient’s XPG expression. Secondary endpoints: Comparison of PFS, overall response rate, duration of response, overall survival and safety profile in XPG-high and XPG-low patients. Assignment: BC patients who have previously received anthracyclins and/or taxanes and who progressed after 2-5 chemotherapy lines will be assigned according to their XPG expression from paraffin embedded tumor samples to stratum A (XPG-high [>3]) or to stratum B (XPG-low [≤3]) (threshold was selected from median XPG expression values observed in a previous trial). Statistical methods: A two-stage design was chosen: at a first stage 20 patients will be enrolled in each stratum. A futility analysis (O’Brien Fleming boundary) based on the primary endpoint (PFS4) will be conducted once 40 evaluable patients have been recruited. If ≥ 7 out of 20 patients achieve PFS4, recruitment will continue to a maximum sample size of 50 evaluable patients per stratum. If ≥ 22 out of 50 patients achieve PFS4, T will be considered active in this group (alpha error: 0.025, power: 80%). To date, 35 patients (16 XPG-high and 15 XPG-low) have been enrolled from three countries and five centers. Recruitment is ongoing.

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.

Phase II study of apatinib plus vinorelbine, a novel combination of all-oral regimen in heavily pretreated patients with metastatic HER2-negative breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1123-TPS1123
Author(s):  
Anjie Zhu ◽  
Peng Yuan ◽  
Jiayu Wang ◽  
Fei Ma ◽  
Yang Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Triple Negative ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Oral Vinorelbine ◽  
Heavily Pretreated

TPS1123 Background: Antiangiogenic therapy in combination with chemotherapy is effective in control advanced breast cancer(ABC). Apatinib is an oral, highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). Phase II clinical trials of Apatinib single agent had presented objective response and manageable toxicity in heavily pretreated, metastatic breast cancer. The median progression free survival (PFS) and median overall survival (OS) of single agent in both triple-negative and non-triple-negative breast cancer were 3.3-4.0 months and 10.3-10.6 months, respectively. The overall response rate and disease control rate (DCR) reached 16.7% and 66.7%, respectively. This all-oral phase II study aims to investigate the efficacy and safety of the oral vinorelbine-Apatinib combination in pre-treated metastatic breast cancer(MBC). Methods: This single arm prospective study enrolled patients with HER2(Human epidermal growth factor receptor-2 ) negative advanced breast cancer, pretreated with anthracycline and taxanes, and who failed in the metastatic setting at least one prior chemotherapy regimen. The estimated Enrollment was 40 patients.The primary end point of this study was PFS. Secondary end points included objective response rate (ORR), DCR, OS and safety. Patients were treated with apatinib 500/425mg daily plus oral vinorelbine 60-80 mg/m2 day1,8,15 every 3 weeks/cycle. Starting doses of Apatinib were chosen according to age, weight and patient status. Patients eligible were evaluated by CT or MRI scan at baseline and every 2 cycles (6 weeks) there after until disease progressed. Adverse events (AEs) were assessed and graded in accordance with the Common Terminology Criteria for AEs, version 4.0. Clinical trial information: NCT02768415.

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