Efficacy and safety of liposomal mitoxantrone (Lipo-MIT) in advanced breast cancer (ABC): A randomized, open label, active-controlled, single-center, phase II clinical trial.

1093 Background: Anthracyclines are associated with cardiotoxicity and myelosuppression in breast cancer (BC) patients. A new drug delivery system, liposomal preparation has shown higher anti-cancer effect and lower toxicity due to modified drug release and particle shape. This trial aimed to evaluate the efficacy and safety of Lipo-MIT in ABC. Methods: This is a randomized, open label, active-controlled, single-center, phase II clinical trial. Eligible patients were randomized in a ratio of 1:1 to receive Lipo-MIT or mitoxantrone hydrochloride injection (MIT) intravenously. The dosage was 20 mg/m2 for Lipo-MIT and 14 mg/m2 for MIT, once every four weeks (i.e., one treatment cycle). The primary endpoint was objective response rate(ORR). The secondary endpoints were progression free survival (PFS) and safety. Results: From Oct 2015 through Jul 2017, 60 patients were randomized to Lipo-MIT group (n = 30) or MIT group (n = 30). The Median (Q1,Q3) age was 56.0 (41.0,62.0) years in Lipo-MIT group and 54.5 (44.0,62.0) years in MIT group. Nineteen patients in Lipo-MIT group and 23 in MIT group received < 4 cycles of treatment, 11 patients in Lipo-MIT group and 7 in MIT group were treated for 4 or more cycles. When Lipo-MIT group was compared with MIT group, ORR was 13.3% (4/30) and 6.7% (2/30), disease control rate (PR+SD) was 50% (15/30) and 30% (9/30), median PFS was 2.30 (95% CI: 1.74-3.91) and 1.86 (95% CI: 1.74-2.40) months ( P> 0.05). Lipo-MIT showed significantly lower incidence of all-grade white blood cell decreased (86.7% vs 96.7%), neutrophil count decreased (80.0% vs 96.7%), conjugated bilirubin increased (53.3% vs 56.7%), aspartate aminotransferase increased (40.0% vs 53.3%), and troponin T increased (3.3% vs 36.7%) than MIT, but higher incidence of anemia (76.7% vs 46.7%), skin hyperpigmentation (66.7% vs 3.3%), and platelet count decreased (56.7% vs 53.3%) than MIT. Conclusions: Lipo-MIT provided numerically better ORR, DCR, and PFS than MIT in ABC. Lower incidence of troponin T increased might suggest lower cardiotoxicity of Lipo-MIT. It is worthwhile to further explore the clinical utility of Lipo-MIT in ABC. Clinical trial information: NCT02596373 .

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Efficacy and safety of mitoxantrone hydrochloride liposome injection in Chinese patients with advanced breast cancer: a randomized, open-label, active-controlled, single-center, phase II clinical trial

Investigational New Drugs ◽

10.1007/s10637-021-01182-7 ◽

2021 ◽

Author(s):

Leiping Wang ◽

Jun Cao ◽

Chunlei Li ◽

Xiaodong Wang ◽

Yannan Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Advanced Breast Cancer ◽

Phase Ii ◽

Phase Ii Clinical Trial ◽

Advanced Breast ◽

Efficacy And Safety ◽

Single Center ◽

Open Label ◽

To Receive

SummaryPurpose. This trial aimed to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection (Lipo-MIT) in advanced breast cancer (ABC). Methods. In this randomized, open-label, active-controlled, single-center, phase II clinical trial, eligible patients were randomized in a ratio of 1:1 to receive Lipo-MIT or mitoxantrone hydrochloride injection (MIT) intravenously. The primary endpoint was objective response rate (ORR). The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), and safety outcomes. Results. Sixty patients were randomized to receive Lipo-MIT or MIT. The ORR was 13.3% (95% confidence interval (CI): 3.8–30.7%) for Lipo-MIT and 6.7% (95% CI: 0.8–22.1%) for MIT. The DCR was 50% (95% CI: 31.3–68.7%) with Lipo-MIT vs. 30% (95% CI: 14.7–49.4%) with MIT. The median PFS was 1.92 months (95% CI: 1.75–3.61) for Lipo-MIT and 1.85 months (95% CI: 1.75–2.02) for MIT. The most common toxicity was myelosuppression. Lipo-MIT resulted in an incidence of 86.7% of leukopenia and 80.0% of neutropenia, which was marginally superior to MIT (96.7% and 96.7%, respectively). Lipo-MIT showed a lower incidence of cardiovascular events (13.3% vs. 20.0%) and increased cardiac troponin T (3.3% vs. 36.7%); but higher incidence of anemia (76.7% vs. 46.7%), skin hyperpigmentation (66.7% vs. 3.3%), and fever (23.3% vs. 10.0%) than MIT. Conclusions The clinical benefit parameters of Lipo-MIT and MIT were comparable. Lipo-MIT provided a different toxicity profile, which might be associated with the altered distribution of the drug. Additional study is needed to elucidate the potential benefit of Lipo-MIT in ABC. Clinical trial registration. This study is registered with ClinicalTrials.gov (No. NCT02596373) on Nov 4, 2015.

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Pragmatic, open-label, single-center, randomized, phase II clinical trial to evaluate the efficacy and safety of methylprednisolone pulses and tacrolimus in patients with severe pneumonia secondary to COVID-19: The TACROVID trial protocol

Contemporary Clinical Trials Communications ◽

10.1016/j.conctc.2021.100716 ◽

2021 ◽

Vol 21 ◽

pp. 100716 ◽

Cited By ~ 1

Author(s):

X. Solanich ◽

A. Antolí ◽

N. Padullés ◽

M. Fanlo-Maresma ◽

A. Iriarte ◽

...

Keyword(s):

Clinical Trial ◽

Phase Ii ◽

Severe Pneumonia ◽

Phase Ii Clinical Trial ◽

Trial Protocol ◽

Efficacy And Safety ◽

Single Center ◽

Open Label ◽

Randomized Phase Ii

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Dual immune checkpoint blockade in advanced well-differentiated neuroendocrine tumors, a phase II clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16201 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16201-e16201

Author(s):

Susan Combs Scott ◽

Ana De Jesus-Acosta ◽

Chen Hu ◽

Benjamin Philip Levy ◽

Valsamo Anagnostou ◽

...

Keyword(s):

Clinical Trial ◽

Neuroendocrine Tumors ◽

Phase Ii ◽

Median Duration ◽

Primary Endpoint ◽

Response Rate ◽

Objective Response ◽

Phase Ii Clinical Trial ◽

Open Label ◽

Well Differentiated

e16201 Background: Limited systemic treatment options are available for progressive well-differentiated neuroendocrine tumors (NET), also called carcinoid tumors. Given emerging evidence for immunotherapy response in high grade NET including small cell lung cancer, we sought to determine the efficacy of combination immunotherapy with ipilimumab and nivolumab in patients with advanced, progressive, well-differentiated NET in an open label phase II clinical trial. Methods: Eligible patients had well-differentiated, nonfunctional NET of lung, pancreas, or GI origin that had progressed within the past 12 months after at least one line of prior therapy. Patients received nivolumab 240 mg every 2 weeks and ipilimumab 1mg/kg every 6 weeks for up to 2 years. Primary endpoint was objective response rate (ORR) by RECIST v1.1. Using a Simon’s 2-stage design, the study planned to accrue up to 56 patients. Based on published response rates to everolimus of 5%, we hypothesized that this regimen would be considered promising if the true ORR is > 15%. Results: Nine patients were enrolled prior to study closure due to funding, including 6 patients with NET of lung origin, 2 pancreatic, and 1 small bowel (Table). Median age was 71 years. All patients had distant metastatic disease at enrollment, with an average of 2 prior lines of therapy. Four of 9 patients achieved the primary endpoint of confirmed objective response, all of whom have ongoing response with a median duration of 15.4 months. Five of 9 patients, including all 4 responders, experienced immune-related toxicity requiring treatment modification or discontinuation. The trial did not accrue the target of 56 patients, however, objective response in 4 of 9 patients (ORR 44.4%, 90% CI: 16.9-74.9%) excluded the response rate target (15%). Conclusions: The impressive ORR of 44% with a median duration of response exceeding 15 months in this small clinical trial warrants further study of combination CTLA-4 and PD-1 inhibition in previously treated well-differentiated NET. Our ongoing immunologic and genomic correlative analysis in responders and non-responders will help inform future study of immunotherapy in this patient population in need of new systemic therapy approaches. Clinical trial information: NCT03420521. [Table: see text]

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