Efficacy and safety of trimethoprim-sulfamethoxazole in HIV-infected patients with cerebral toxoplasmosis in Brazil: a single-arm open-label clinical trial

2019 ◽  
Vol 30 (12) ◽  
pp. 1156-1162 ◽  
Author(s):  
Daniela Pellegrino ◽  
Ronaldo Gryschek ◽  
Augusto César Penalva de Oliveira ◽  
Rosa Marcusso ◽  
Ademir Correia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Clinical Manifestations ◽  
Altered Mental Status ◽  
Tertiary Hospital ◽  
High Morbidity ◽  
Cerebral Toxoplasmosis ◽  
Efficacy And Safety ◽  
Open Label ◽  
Radiological Response

Cerebral toxoplasmosis continues to cause high morbidity and mortality in developing countries. The association of sulfadiazine and pyrimethamine is considered the standard therapy; however, it has potential disadvantages. This single-arm open-label clinical trial was carried out in a tertiary hospital in São Paulo, Brazil. We included patients of at least 18 years of age, whose HIV infection was confirmed, and clinical and brain computed tomography (CT) findings were compatible with cerebral toxoplasmosis upon admission. Patients received trimethoprim (TMP) 10 mg/kg/day sulfamethoxazole (SMX) 50 mg/kg/day, in two divided doses. Brain CT was performed at study entry and after two weeks. The endpoints of the study were: (i) the proportion of patients with clinical and radiological response after two weeks of TMP-SMX and (ii) the proportion of patients who discontinued TMP-SMX due to adverse events. Forty-six patients were included (23 males, median age 35 years). The main clinical manifestations were headache, hemiparesis and altered mental status. The proportion of patients who obtained clinical and radiological response after two weeks of anti-toxoplasma treatment was 85% (n = 39). Overall, TMP-SMX was safe, with only 2 (4%) discontinuations due to adverse events. In this study, TMP-SMX was effective and safe in the treatment of HIV-related cerebral toxoplasmosis.

Update results of paclitaxel and cisplatin in combination with anlotinib as first-line regimen for patients with advanced ESCC: A multicenter, single-arm, open-label phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16013-e16013
Author(s):  
Junsheng Wang ◽  
Tao Wu ◽  
Suxia Luo ◽  
Ning Li ◽  
Yonggui Hong ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Safety Profile ◽  
Locally Advanced ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Common

e16013 Background: Paclitaxel combined with cisplatin regimen has been the standard first-line therapy in advanced Esophageal Squamous Cell Carcinoma (ESCC) for almost two decades. However, the 5-year survival rate was only 4.8% in advanced ESCC. Therefore, more effective therapeutic treatments were needed to prolong the survival urgently. Anlotinib was demonstrated to be an effective second-line monotherapy for patients with advanced or recurrent ESCC in China. And the preliminary results of our trial had been reported in 2020 ESMO (Abs 1448) and 2021 ASCO-GI Symposium (Abs 181). Consequently, this study was to investigate the efficacy and safety of paclitaxel and cisplatin combined with anlotinib as first-line therapy in advanced ESCC and report the update results regularly. Methods: Pts with previously untreated metastatic or unresectable, locally advanced ESCC, who had not received (neo) adjuvant therapy/radical surgery within 6 months were recruited in this study. Eligible patients were given paclitaxel (135mg/m2, iv, q3w) and cisplatin (60̃75mg/m2, iv, d1̃3, q3w) plus anlotinib (10mg, po, d1̃14, q3w) for 4̃6 cycles as initial therapy. For those who did not have disease progression, maintenance treatment was treated with anlotinib monotherapy (10mg, po, d1̃14, q3w) until progression or unacceptable toxicity. The tumor response was assessed by investigator according to RECIST version 1.1 criteria using computed tomography scans every two cycles. The predefined sample size was 47. The primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and DOR. Results: From Oct 2019 to Dec 2020, a total of 45 patients were enrolled. Among 34 pts who were available for efficacy and safety evaluation. there were 1 confirmed CR (2.9%), 26 confirmed PR (76.5%), 2 unconfirmed PR (5.9%) and 5 SD (14.7%). Consequently, ORR was 79.4% (95%CI: 62.1̃91.3) and DCR was 100.0% (95%CI: 89.7̃100.0). At the data cut-off date, 11 patients discontinued treatment due to PD, the preliminary prognostic result indicated that the median PFS of the 34 patients was 9.76 months (95%CI: 8.44-13.08). And the median OS was not yet available. Additionally, safety profile exhibited that the common drug-related adverse events were myelosuppression, gastrointestinal reaction, fatigue, hypertension, constipation, hypokalemia, hepatotoxicity and hemoptysis. And the common grade ≥3 adverse events were myelosuppression (20.6%), hypertension (8.8%), nausea and vomit (5.9%), fatigue (5.9%) and hypokalemia (5.9%). Conclusions: The update results suggested that the regimen of paclitaxel and cisplatin combined with anlotinib as first-line therapy for advanced ESCC exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: NCT04063683.

ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC—A single-arm, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 70-70
Author(s):  
Jin Yan ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Yunwei Han ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Performance Status ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
Multicenter Phase ◽  
First Line Treatment

70 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is considered as the standard first-line therapy for metastatic colorectal cancer (mCRC), and maintenance treatment is proven to be a promising and controversial therapeutic strategy which is mainly involved bevacizumab or capecitabine. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib is a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously. Previous studies indicated that anlotinib demonstrated clinical benefits for patients with mCRC. This study aimed to evaluate the efficacy and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib maintenance therapy for mCRC. Methods: ALTER-C-001 trial was an open label, single-arm, multicenter phase II study. A calculated sample size of 53 patients with previously untreated mCRC, ranging from 18-75 years old and an ECOG performance status ≤ 1 were planned to recruit. Eligible patients were treated with capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) for 6 cycles followed by maintenance therapy of anlotinib (12mg, po, d1~14, q3w) until disease progression or intolerable adverse events (AEs). The primary endpoint was progression-free survival (PFS). Secondary endpoints were ORR, DCR, DOR and safety. Results: From January 2020 to September 2020, a total of 9 patients were enrolled, 6 patients were available for efficacy assessment. In best overall response assessment (all confirmed), there were 66.7% PR (4/6), 16.7% SD (1/6) and 16.7% PD (1/6). The preliminary ORR and DCR of the 6 patients was 66.7% (95% CI, 22.3-95.7%) and 83.3% (95% CI, 35.9-99.6%), respectively. The median PFS was not reached. Most treatment-related adverse events (TRAEs) were grade 1-2. Grade 3 or above TRAEs were as follows: hypertriglyceridemia (33.3%), hypertension (16.7%), neutropenia (16.7%) and lipase elevated (16.7%). No grade 5 AEs were observed. Conclusions: The preliminary results indicated that anlotinib plus XELOX regimen followed by anlotinib monotherapy as first-line treatment exhibited antitumor efficacy and manageable toxicity for patients with mCRC. The study is still ongoing and the data will be updated subsequently. Clinical trial information: ChiCTR1900028417.

Topical oxygen therapy in the treatment of diabetic foot ulcers: a multicentre, open, randomised controlled clinical trial

2021 ◽  
Vol 30 (Sup5) ◽  
pp. S7-S14
Author(s):  
Thomas E Serena ◽  
Neal M Bullock ◽  
Windy Cole ◽  
John Lantis ◽  
Lam Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Diabetic Foot ◽  
Oxygen Therapy ◽  
Wound Closure ◽  
Foot Ulcers ◽  
Controlled Clinical Trial ◽  
Diabetic Foot Ulcers ◽  
Open Label ◽  
Number Of Patients

Objectives: Perfusion and blood oxygen levels are frequently insufficient in patients with hard-to-heal wounds due to poor circulation, vascular disruption and vasoconstriction, reducing the wound's capacity to heal. This study aimed to investigate the effect of topical oxygen on healing rates in patients with hard-to-heal diabetic foot ulcers (DFUs) (i.e., non-responsive over four weeks). Method: This multicentre, open-label, community-based randomised clinical trial compared standard care (SOC) with or without continuous topical oxygen therapy (TOT) for 12 weeks in patients with DFUs or minor amputation wounds. SOC included debridement, offloading with total contact casting (TCC) and appropriate moisture balance. Primary endpoints were the number of patients to achieve complete wound closure and percentage change in ulcer size. Secondary endpoints were pain levels and adverse events. Results: For the study, 145 patients were randomised with index ulcers graded Infectious Diseases Society of America (IDSA) 1 or 2, or Wagner 1 or 2. In the intention-to-treat analysis, 18/64 (28.1%) patients healed in the SOC group at 12 weeks compared with 36/81 (44.4%) in the SOC plus TOT group (p=0.044). There was a statistically significant reduction in wound area between the groups: SOC group mean reduction: 40% (standard deviation (SD) 72.1); SOC plus TOT group mean reduction: 70% (SD 45.5); per protocol p=0.005). There were no significant differences in changes to pain levels or adverse events. Conclusion: This study suggests that the addition of TOT to SOC facilitates wound closure in patients with hard-to-heal DFUs.

scholarly journals 413 Toripalimab in combination with concurrent chemoradiation in patients with advanced/metastatic esophageal carcinoma: protocol for a single-arm, prospective, open-label, phase II clinical trial

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A444-A444
Author(s):  
Lei Wu ◽  
Yi Wang ◽  
Gang Wan ◽  
Jiahua Lv ◽  
Qifeng Wang ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Stage Iv ◽  
Predictive Biomarkers ◽  
Primary Objective ◽  
High Morbidity ◽  
Efficacy And Safety ◽  
Open Label ◽  
Carboplatin Auc

BackgroundEsophageal carcinoma is a disease with high morbidity and mortality in China and, recently, Immune checkpoint inhibitors(ICIs) combined with chemotherapy have shown good efficacy and safety for treatment; however, some patients still suffer from tumor progression or metastasis after treatment. Clinical studies have confirmed that immunotherapy combined with chemoradiotherapy can significantly improve the prognosis of patients with advanced esophageal cancer, but the efficacy and safety of adding radiotherapy to immunotherapy and chemotherapy have been less reported.MethodsThis is an open-label, single-arm, and single-center phase ll trial.Patients with unresectable stage IV esophageal squamous cell carcinoma(ESCC) who had not received prior systemic therapy were enrolled. The patients were treated with two cycles of toripalimab (240 mg d1, Q3W) combined with induction chemotherapy (paclitaxel 135–175 mg/m2, d1+carboplatin AUC=4–6, d1, Q3W), sequentially combined with concurrent chemoradiotherapy (30–50 Gy in 15–25 fractions, paclitaxel 135–175 mg/m2, d1+carboplatin AUC=4–6 d1, Q3W), followed by maintenance treatment with toripalimab (240 mg d1, Q3W) for 1 year. The primary objective of this trial is to evaluate the progression-free survival (PFS) of this combination therapy;and the secondary objective is related to the assessment of objective response rate (ORR), the disease control rate (DCR), the duration of remission (DOR), the 1- and 2-year overall survival(OS) rates, the safety and tolerability of patients to treatment, and the identification of the changes in the health-related quality of life (HRQoL) of patients. Furthermore, we aimed to identify predictive biomarkers (such as the expression of PD-L1 ctDNA and cytokines) and to explore the relationship between these biomarkers and tumor response to the study treatment.AcknowledgementsWe thank all the participants and their advisors involving in this study. We owe thanks to the patients in our study and their family members.Trial RegistrationChiCTR(ChiCTR2100046715). Registered on the 27th of May 2021.Ethics ApprovalThe study protocol is approved by Ethics Committee of Sichuan Cancer Hospital (SCCHEC-02-2021-021).Changes to the protocol will be communicated via protocol amendment by the study principal investigators. Written informed consent will be obtained from all participants.

Selpercatinib efficacy and safety in patients with RET-altered thyroid cancer: A clinical trial update.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6073-6073
Author(s):  
Eric Jeffrey Sherman ◽  
Lori J. Wirth ◽  
Manisha H. Shah ◽  
Maria E. Cabanillas ◽  
Bruce Robinson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Thyroid Cancer ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Integrated Analysis ◽  
Low Grade ◽  
Efficacy And Safety ◽  
Thyroid Cancers ◽  
Altered Thyroid

6073 Background: Selpercatinib, is a first-in-class, highly selective, CNS active and potent RET inhibitor approved in multiple countries for treatment of RET-fusion positive lung or thyroid cancers. Reported is an update of efficacy and safety results in RET-altered thyroid cancer, with a longer follow up (30 Mar 2020 data cutoff vs 16 Dec 2019) and additional enrolment. Methods: Patients (pts) with RET-mutant medullary thyroid cancer (MTC) and RET-fusion positive thyroid cancer (TC) were enrolled in the global (16 countries, 89 sites) Phase 1/2 LIBRETTO-001 trial (NCT03157128). The primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent review committee (IRC). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), clinical benefit rate (CBR; CR+PR+SD ≥16 weeks), and safety. The integrated analysis set (IAS, n = 143) includes efficacy evaluable MTC pts previously treated with cabozantinib and/or vandetanib (cabo/vande). The primary analysis set (PAS), a subset of IAS, is the first 55 enrolled pts. Cabo/vande naïve MTC pts (N = 112) and TC pts with prior systemic treatment (N = 22) were also analyzed. Safety population includes all pts who received ≥1 dose of selpercatinib (MTC N = 315; TC N = 42) by data cutoff. Results: For MTC patients, the ORR for IAS was 69.2%, in the PAS it was 69.1%, and 71.4% for cabo/vande naïve MTC pts. The ORR for TC pts (n = 22) was 77.3% (see table). Most treatment-emergent adverse events (TEAEs) were low grade; the most common (≥25% of MTC and/or TC pts treated with selpercatinib) were dry mouth, diarrhea, hypertension, fatigue and constipation for both MTC and TC pts, increased ALT/AST, peripheral edema and headache in MTC pts and nausea in TC pts. 4.8% of MTC and TC pts discontinued selpercatinib due to TEAEs but only 1.9% with MTC and none with TC discontinued due to treatment-related adverse events. Conclusions: In this updated analysis, selpercatinib continued to show marked and durable antitumor activity in pts with RET-altered thyroid cancers. Selpercatinib was well tolerated and no new safety concerns were identified. A global, randomized, phase 3 trial (LIBRETTO-531) evaluating selpercatinib compared to cabo/vande in kinase inhibitor naïve MTC pts is ongoing. Clinical trial information: NCT03157128. [Table: see text]

Update results from ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC-A single-arm, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15550-e15550
Author(s):  
Jin Yan ◽  
Yunwei Han ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Multicenter Phase ◽  
First Line Treatment

e15550 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC), and the followed maintenance treatment is an optional approach to balance the efficacy and toxicity. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib, a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously, substantially prolonged the PFS with manageable toxicity for refractory mCRC in the phase III ALTER0703 clinical trial. Here we report an update on the effectiveness and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib monotherapy for mCRC. Methods: In this open label, single-arm, multicenter phase II clinical trial, 53 mCRC patients without prior systemic treated, aged 18-75 and an ECOG performance status of 0 or 1 were planned to recruit. Eligible patients received capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1̃14, q3w) treatment for 6 cycles. After 6 cycles of inducing therapy, patients would receive anlotinib (12mg, po, d1̃14, q3w) as maintenance therapy until disease progression or intolerable adverse events (AEs). The primary endpoint was PFS; Secondary endpoints included ORR, DCR, DOR and safety. Results: By the data analysis cutoff date of January 22, 2021, a total of 18 patients were enrolled, of which 12 patients were available for efficacy assessment. In best overall response assessment, there were 50.0% PR (6/12), 33.3% SD (4/12) and 16.7% PD (2/12). The ORR was 50.0% (95% CI, 21.1-78.9%) and DCR was 83.3% (95% CI, 51.5-97.9%). The longest duration of treatment was 8.8 months and the response was still ongoing. The median PFS was not reached. The most common treatment related adverse events (TRAEs) of any grade (≥20%) were leukopenia, hypertension, neutropenia, diarrhea, fatigue, hypertriglyceridemia. Grade 3/4 TRAEs included hypertension (22.2%), hypertriglyceridemia (11.1%), lipase elevated (11.1%) and neutropenia (5.6%). No grade 5 AEs occurred. Conclusions: The update results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy showed promising anti-tumor activity and manageable safety for patients with mCRC. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: ChiCTR1900028417.

The efficacy and safety of anlotinib in neoadjuvant treatment in locally advanced thyroid cancer: A single-arm phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6069-6069
Author(s):  
Naisi Huang ◽  
Guohua Sun ◽  
Yulong Wang ◽  
Jiaying Chen ◽  
Qing Guan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Thyroid Cancer ◽  
Adverse Events ◽  
Objective Response ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Primary Treatment ◽  
Tumor Diameter ◽  
Efficacy And Safety ◽  
Advanced Thyroid Cancer

6069 Background: Surgery is the primary treatment for locally advanced thyroid cancer (TC). For some locally advanced TC, R0/R1 resection could not be achieved at initial diagnosis and neoadjuvant treatment would be an option. However, there is still little evidence regarding neoadjuvant treatment in locally advanced TC. Methods: This single-arm, phase 2 study investigated the efficacy and safety of Anlotinib (12mg orally daily, for two weeks on/on week off) for 2-6 cycles in patients with locally advanced TC in the neoadjuvant setting. Operable patients received surgery after neoadjuvant treatment. The primary endpoint was objective response rate (ORR). Results: A total of 13 patients were included and received an average of 3.5 cycles (range: 3-6 cycles) of Anlotinib treatment. 12 cases were papillary thyroid cancer, and 1 was follicular thyroid cancer. The ORR of Anlotinib was 76.9% with 10 partial response (PR), 2 stable disease (SD), and 1 progressive disease (PD). 8 PR and 1 SD patients received surgery after neoadjuvant treatment, of whom 8 had R0/1 resections and 1 had R2 resection. 2 PR patients refused to have surgery and the rest 2 patients were not operable. The R0/1 resection rate for intent to treat population was 61.5% and for per-protocol population was 72.7%. The maximum reduction in sum of tumor diameter was an average of 34.8% (range: 30.9%-45.5%) for PR patients. Most adverse events were grade 1 or 2. Common adverse events of all grade were hypertension (76.9%), hypertriglyceridemia (69.2%), proteinuria (53.8%), TSH increase (53.8%), cholesterol elevation (53.8%) and hand-foot syndrome (38.5%). The majority of adverse events discontinued after the neoadjuvant treatment stopped. Conclusions: Anlotinib demonstrated antitumor activity in the neoadjuvant treatment in locally advanced TC and the majority of patients achieved R0/1 resection. Adverse events were consistent with the known Anlotinib adverse event profile. These results suggest that Anlotinib neoadjuvant treatment represents a new option for locally advanced TC. Clinical trial information: NCT04309136.

Sign in / Sign up

Export Citation Format

Share Document