RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 5-5 ◽  
Author(s):  
Charles S. Fuchs ◽  
Kohei Shitara ◽  
Maria Di Bartolomeo ◽  
Sara Lonardi ◽  
Salah-Eddin Al-Batran ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Primary Endpoint ◽  
Human Monoclonal Antibody ◽  
Single Agent ◽  
Phase Iii ◽  
First Line ◽  
Double Blind ◽  
Double Blind Placebo ◽  
To Receive ◽  
Line Chemotherapy

5 Background: Ramucirumab, a VEGFR-2 IgG1 human monoclonal antibody, is the only biologic with proven efficacy as both a single-agent and in combination with paclitaxel in the second-line treatment of G-GEJ adenocarcinoma. RAINFALL (NCT02314117) is a global, double-blind, placebo-controlled randomized clinical trial addressing the hypothesis that adding ramucirumab to first-line Cis plus Cape or 5-fluorouracil (5FU) produces significant clinical benefit. Methods: Metastatic G-GEJ cancer patients eligible for first-line chemotherapy with ECOG performance status 0-1 were randomized 1:1 to receive either RAM (8 mg/kg iv D1, D8) or placebo (PL), every 21d. All patients received Cape (or 5FU)+Cis. Cis was given for up to 6 cycles. Cape+RAM/placebo was continued until progressive disease, toxicity or other discontinuation criteria. The primary endpoint was progression-free survival (PFS) for the first 508 patients; overall survival (OS) for ITT population was a powered secondary endpoint. Results: 645 patients were randomized to receive RAM+Cape/Cis (n=326) or PL+Cape/Cis (n=319). PFS was significantly prolonged in patients treated with RAM+Cape/Cis versus PL+Cape/Cis (HR, 0.75; 95% CI 0.61–0.94; p=0.011; median, 5.7 vs 5.4 mos), meeting the primary endpoint. There was no survival benefit for patients treated with RAM+Cape/Cis versus PL+Cape/Cis (HR, 0.96; 95% CI 0.80–1.16; p=0.68; median, 11.2 vs 10.7 mos). ORR in the ITT population was 41.1% in the RAM arm (95% CI 35.8–46.4) and 36.4% (95% CI 31.1–41.6) in the PL arm. Grade ≥3 adverse events in ≥10% of patients in the RAM arm were: neutropenia (26.3% RAM; 27.0% PL), anemia (12.1% RAM; 14.0% PL), and hypertension (9.9% RAM; 1.6% PL). No new safety signals were observed. Conclusions: In treatment-naïve patients with metastatic G-GEJ adenocarcinoma, the addition of ramucirumab to first-line chemotherapy conferred a significant 25% reduction in the risk of disease progression or death in the primary endpoint of PFS; however, ramucirumab was not associated with an improved OS. Clinical trial information: NCT02314117.

Phase III trial comparing XELOX regimen (oxaliplatin plus capecitabine) versus EOX regimen (epirubicin, oxaliplatin and capecitabine) as first-line treatment for advanced gastric cancer: EXELOX trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4014-4014
Author(s):  
Weijian Guo ◽  
Xiaodong Zhu ◽  
Mingzhu Huang ◽  
Yusheng Wang ◽  
Zhiyu Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Phase Iii Trial ◽  
Grade 3 ◽  
To Receive ◽  
Line Chemotherapy ◽  
First Line Treatment

4014 Background: At present, there is no standard chemotherapy regimen for advanced gastric cancer (AGC), and there is no consensus whether the three-drug combination is better than two-drug combination in first-line treatment. Both of XELOX regimen and EOX regimen are widely recommended as firs-line chemotherapy regimens for AGC. In this EXELOX trial, we aimed to compare the efficacy and safety of EOX and XELOX regimens. Methods: EXELOX is an open-label, multicenter, prospective, randomized phase III trial that enrolled 448 previously untreated patients with histologically confirmed advanced gastric adenocarcinoma from 7 hospitals in China. Patients were randomly assigned (1:1) to receive XELOX regimen (oxaliplatin 130mg/m2 d1; xeloda 1000mg/m2 bid d1-14) or EOX regimen (epirubicin 50mg/m2 d1; oxaliplatin 130mg/m2 d1; xeloda 1000mg/m2 bid d1-14) in this study. Treatment was repeated every 3 weeks until disease progression, intolerable toxicity, patient death, withdrawal of informed consent, or up to eight cycles, followed by xeloda single-agent maintenance. We stratified randomization by Eastern Cooperative Oncology Group status, extent of disease(locally advanced/metastatic) and clinical trial center. Patients and clinicians were not masked to the allocated treatment. The primary endpoint was progression-free survival (PFS) on an intention-to-treat basis with a non-inferiority upper margin of 1.3 for the hazard ratio (HR). The clinical trial was a non-inferiority study that was registered with ClinicalTrials.gov, Number NCT02395640. The study is ongoing, but no longer recruit new participants. Results: Between Apr 10,2015 and Aug 20,2020, a total of 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). In ITT basis, the median PFS was 5.0 months (95%CI 4.5-6.0) in XELOX group and 5.5 months (95%CI 5.0-6.0) in EOX group (HR 0.989, 95%CI 0.812-1.203; Pnon-inferiority= 0.0032). In Per-protocol population (n = 428), the median PFS was 5.0 months (95%CI 5.0-6.0) in XELOX group and 5.5 months (95%CI 5.0-6.0) in EOX group (HR 0.983, 95%CI 0.807-1.198; Pnon-inferiority= 0.0028). The incidence of grade 3-4 adverse events (AEs) was 42.2% (90/213) in XELOX group and 72.5(156/215) in EOX group ( p= 0.001). The most common grade 3-4 AEs were neutropenia (affecting 13.1% (28/213) in XELOX group and 48.4%(104/215) in EOX group ( p= 0.000). The incidence of chemotherapy dose reduction was 35% (75/213) in XELOX group and 55% (120/215) in EOX group( p= 0.009). One treatment-related death (lung infection) was observed in EOX group, and none in XELOX group. Conclusions: XELOX regimen is noninferior to EOX regimen in PFS with a better safety profile as first-line treatment for AGC patients, therefore XELOX is a more favorable choice and might be one of the standard first-line chemotherapy regimens. Clinical trial information: NCT02395640.

scholarly journals Efficacy and safety of netakimab, a novel anti-IL-17 monoclonal antibody, in patients with moderate to severe plaque psoriasis. Results of a 54-week randomized double-blind placebo-controlled PLANETA clinical trial

2021 ◽  
Vol 97 (4) ◽  
pp. 80-91
Author(s):  
Luis Puig ◽  
Andrey L. Bakulev ◽  
Muza M. Kokhan ◽  
Alexey V. Samtsov ◽  
Vladislav R. Khairutdinov ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Monoclonal Antibody ◽  
Plaque Psoriasis ◽  
Safety Data ◽  
Interleukin 17 ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Severe Plaque Psoriasis ◽  
To Receive

Background. Netakimab (NTK), an original humanized anti-interleukin-17 monoclonal antibody, showed therapeutic efficacy in moderate to severe plaque psoriasis in a phase 2 clinical study. Herein we report the results of 54 weeks of a phase 3 trial. Aim. To evaluate the efficacy and safety of two NTK regimens vs. placebo in moderate to severe plaque psoriasis. Methods. PLANETA is the ongoing randomized double-blind placebo-controlled clinical trial. 213 patients with moderate to severe plaque psoriasis were randomly assigned to receive NTK 120 mg once every 2 weeks (NTK Q2W), NTK 120 mg once every 4 weeks (NTK Q4W) or placebo. During the first 3 weeks, patients received subcutaneous injections of NTK or placebo (according to the allocation) once a week. Patients in the NTK Q2W group then received NTK at weeks 4, 6, 8, and 10. Subjects in the NTK Q4W group received NTK at weeks 6 and 10 and placebo at weeks 4 and 8. Patients in the placebo group received placebo injections at weeks 4, 6, 8, and 10. Treatment was unblinded at week 12. During the open-label phase, patients in both NTK groups continued to receive NTK Q4W. The primary efficacy endpoint was the proportion of patients in each group who achieved a 75% or greater reduction from baseline in psoriasis area and severity index (PASI 75) at week 12. Results. A total of 77.7%, 83.3%, and 0% of patients had a PASI 75 response at week 12 in the NTK Q2W, NTK Q4W, and placebo groups, respectively (P 0.0001, Fishers exact test, ITT). The effect was maintained throughout the 1-year treatment. NTK showed a good safety profile and low immunogenicity. Conclusion. Treatment with NTK results in high rates of sustained clinical response in patients with moderate to severe plaque psoriasis. The study is ongoing; thus, long-term use efficacy and safety data are forthcoming.

Sign in / Sign up

Export Citation Format

Share Document