Phase III study of APF530 versus ondansetron with a neurokinin 1 antagonist + corticosteroid in preventing highly emetogenic chemotherapy-induced nausea and vomiting: MAGIC trial.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 68-68
Author(s):  
Ian D. Schnadig ◽  
Richy Agajanian ◽  
Shaker R. Dakhil ◽  
Nashat Y. Gabrail ◽  
Robert E. Smith ◽  
...  
Keyword(s):  
Unmet Need ◽  
Complete Response ◽  
Drug Regimen ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Complete Control ◽  
Delayed Phase

68 Background: Managing chemotherapy-induced nausea and vomiting (CINV) associated with delayed ( > 24-120 h) highly emetogenic chemotherapy (HEC) is an unmet need. APF530, extended-release granisetron, provides sustained release over ≥ 5 days to prevent acute (0-24 h) and delayed CINV. This trial compared the efficacy and safety of APF530 in preventing CINV after HEC in a 3-drug regimen vs a standard 3-drug regimen with ondansetron (Ond). Methods: In this double-blind, multicenter study (NCT02106494), patients (pts) receiving single-day HEC (2011 ASCO guidelines) were randomized 1:1 to APF530 500 mg SC (10 mg granisetron) or Ond 0.15 mg/kg IV and stratified by cisplatin ( ≥ 50 mg/m2, yes/no). Pts were scheduled to receive concomitant dexamethasone (Dex) 12 mg IV + fosaprepitant (Fos) 150 mg IV on day 1 + PO Dex on days 2-4. The primary end point was delayed-phase complete response (CR) (no emesis, no rescue medication). Secondary end points included CR in acute and overall phases and complete control (CC; CR and no more than mild nausea) in acute, delayed, and overall phases. Treatment (tx) comparisons used chi-square test controlling for cisplatin. Adverse events (AEs) and injection-site reactions (ISRs) were assessed. Results: Modified intent-to-treat analysis included 902 pts (APF530, n = 450; Ond, n = 452) with baseline demographics balanced between tx groups. A significantly higher % of APF530 (65%) vs Ond (57%) pts had delayed-phase CR (P= .014). A significantly higher % of APF530 (61%) vs Ond (53%) pts had delayed-phase CC (P= .022, Table). CR and CC rates in acute and overall phases were numerically higher with APF530 vs Ond, but not statistically significant. APF530 was well tolerated. Most common AEs were ISRs, mostly mild or moderate. Conclusions: APF530 with Fos+Dex led to statistically higher CR and CC rates in delayed-phase CINV with HEC vs a standard 3-drug regimen of Ond with Fos+Dex. Clinical trial information: NCT02106494. [Table: see text]

Efficacy of Thalidomide in Preventing Delayed Nausea and Vomiting Induced by Highly Emetogenic Chemotherapy: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Trial (CLOG1302 study)

2017 ◽  
Vol 35 (31) ◽  
pp. 3558-3565 ◽  
Author(s):  
Lingyun Zhang ◽  
Xiujuan Qu ◽  
Yuee Teng ◽  
Jing Shi ◽  
Ping Yu ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Delayed Nausea

Purpose We examined the efficacy and safety of thalidomide (THD) for the prevention of delayed nausea and vomiting in patients who received highly emetogenic chemotherapy (HEC). Patients and Methods In a randomized, double-blind, active-controlled, phase III trial, chemotherapy-naive patients with cancer who were scheduled to receive HEC that contained cisplatin or cyclophosphamide-doxorubicin/epirubincin ≥ 50 mg/m2 regimens were randomly assigned to a THD group (100 mg twice daily on days 1 to 5) or placebo group, both with palonosetron (0.25 mg on day 1) and dexamethasone (12 mg on day 1; 8 mg on days 2 to 4). Primary end point was complete response to vomiting—no emesis or use of rescue medication—in the delayed phase (25 to 120 h). Nausea and anorexia on days 1 to 5 were evaluated by the 4-point Likert scale (0, no symptoms; 3, severe). Quality of life was assessed by the European Organization for Research and Treatment of Cancer QLQ-C30 version 3 questionnaire on days −1 and 6. Results Of 656 patients, 638 were evaluable: 317 in the THD group and 321 in the control group. Compared with placebo, delayed and overall (0 to 120 h) complete response rates to vomiting were significantly higher with THD: 76.9% versus 61.7% ( P < .001) and 66.1% versus 53.3% ( P = .001), respectively. Rates of no nausea were also higher in the THD group (delayed: 47.3% v 33.3%; P < .001; overall: 41% v 29.6%; P = .003), and mean scores of anorexia were lower overall (0.44 ± 0.717 v 0.64 ± 0.844; P = .003). Adverse effects were mild to moderate. The THD group had increased sedation, dizziness, constipation, and dry mouth, but experienced better quality of life after chemotherapy. Conclusion Thalidomide combined with palonosetron and dexamethasone significantly improved HEC-induced delayed nausea and vomiting prevention in chemotherapy-naive patients.

Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC): Alliance A221301, a randomized, double-blind, placebo-controlled trial.

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 176-176 ◽  
Author(s):  
Rudolph M. Navari ◽  
Rui Qin ◽  
Kathryn Jean Ruddy ◽  
Heshan Liu ◽  
Steven Francis Powell ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Secondary Endpoint ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Grade 3

176 Background: The purpose of the study was to determine the effectiveness of olanzapine (OLN) for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC). Methods: A randomized, double-blind, phase III trial was performed in chemotherapy-naïve patients receiving cisplatin, > 70 mg/m2, or cyclophosphamide-anthracycline-based chemotherapy, comparing OLN to placebo in combination with aprepitant (APR), a 5-HT3 receptor antagonist (5-HT3), and dexamethasone (DEX). The OLN regimen was 10 mg of oral OLN, 125 mg APR, a 5-HT3, and oral DEX 12 mg pre-chemotherapy, day 1, and 10 mg/day of oral OLN and 8 mg DEX on days 2-4 post-chemotherapy plus 80 mg APR on days 2, 3 post-chemotherapy. The placebo (PLA) regimen was oral placebo, pre-chemotherapy, day 1, and on days 2-4 post-chemotherapy; the APR, 5-HT3, and DEX pre- and post-chemotherapy were identical to that used in the OLN regimen. Fosaprepitant (150 mg IV), day 1 was allowed for substitution for the oral aprepitant. Palonosetron, ondansetron, or granisetron were the permitted 5-HT3 options. Nausea was measured on a 0-10 visual analogue scale, with 0 being “no nausea at all” and 10 being “nausea as bad as it can be”. No nausea was the primary endpoint and, complete response (no emesis and no use of rescue medications) was a secondary endpoint. Results: 401 patients (202 OLN, 199 PLA) were enrolled in the study. The proportion of patients who had no nausea was significantly greater for the OLN regimen compared to the PLA regimen for the acute period (24h post-chemotherapy) (74% vs. 45%, p < 0.0006), for the delayed period ( 24-120 h post-chemotherapy) (43% vs. 26%, p < 0.0006), and for the overall period (0-120 h) (39% vs. 22%, p < 0.0006). Complete response was significantly improved for the OLN patients compared to PLA patients for the acute (85% vs. 65%, p < 0.0001), the delayed (67% vs. 53%, p < 0.0078), and the overall periods (64% vs. 41%, p < 0.0001). There were no grade 3 or 4 toxicities. Conclusions: No nausea, the primary endpoint, and complete response, a secondary endpoint, were significantly improved with OLN, compared to PLA. Clinical trial information: NCT02116530.

A phase III, randomized, double-blind, multicenter, active control study of fosnetupitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC): CONSOLE.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12099-12099
Author(s):  
Yoshimasa Shiraishi ◽  
Akito Hata ◽  
Naoki Inui ◽  
Morihito Okada ◽  
Masahiro Morise ◽  
...  
Keyword(s):  
Study Drug ◽  
Incidence Rates ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Secondary Endpoints ◽  
To Receive ◽  
Age Category

12099 Background: Fosnetupitant (FN) is a phosphorylated pro-drug of netupitant that has high binding affinity for the neurokinin-1 (NK-1) receptor and a long half-life of 70 h. This phase 3 study is the first head-to-head study to compare two NK-1 receptor antagonists, FN and fosaprepitant (FA), in combination with palonosetron and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (JapicCTI-194611). Methods: Patients scheduled to receive cisplatin (≥70 mg/m2) -based chemotherapy were randomly assigned 1:1 to receive FN 235 mg or FA 150 mg, in combination with palonosetron 0.75 mg and dexamethasone (9.9 mg on day 1, 6.6 mg on days 2-4). The stratification factors were sex, age category (<55 vs. ≥55 years), and site. The primary endpoint was the complete response (CR; no emetic events and no rescue medication) rate, stratified by sex and age category, during the overall phase (0-120 h) to show the non-inferiority (margin, -10%) of FN to FA. The secondary endpoints were: CR rate, complete protection rate, total control rate, no nausea rate, no emetic events rate in each period [i.e., acute (0-24 h), delayed (24-120 h), overall, 0-168 h and 120-168 h], time to treatment failure, and safety, including injection site reactions (ISRs). Assessment of efficacy was continued until 168 h after the initiation of cisplatin. Some eligible patients were evaluated for safety and efficacy of FN for up to four cycles. Results: Between February 2019 and March 2020, total 795 patients were enrolled in the study. The study drug was administered to 785 patients (n=392 in FN vs. n=393 in FA), and all of them were evaluated for efficacy and safety. Baseline characteristics were generally balanced between the two groups. The adjusted overall CR rate was 75.2% in FN vs. 71.0% in FA [MH common risk difference, 4.1%; 95% CI, -2.1% to 10.3%), thus demonstrating non-inferiority of FN to FA. Regarding the other secondary endpoints of efficacy until 168 h, FN was favorable against FA, especially the CR rate during 0-168 h (73.2% in FN vs. 66.9% in FA) (Table). The incidence rates of treatment-related adverse events were 22.2% in FN vs. 25.4% in FA, whereas those of ISRs with any cause or with treatment-related were 11.0% or 0.3% in FN vs 20.6% or 3.6% in FA, respectively ( p<0.001). Conclusions: FN demonstrated non-inferiority to FA, with a favorable safety profile and lower risk for ISRs. For the period beyond 120 h after initiation of chemotherapy, FN may have the potential to improve the prevention of “beyond delayed” CINV. Clinical trial information: JapicCTI-194611. [Table: see text]

Impact on patients’ daily life activities of NEPA, the oral fixed-dose combination of netupitant, a new NK1 receptor antagonist (RA), and palonosetron (PALO) plus dexamethasone (DEX) versus PALO plus DEX for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC).

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 66-66 ◽  
Author(s):  
Matti S. Aapro ◽  
Giorgia Rossi ◽  
Giada Rizzi ◽  
Maria Elisa Borroni ◽  
Norman G. Nagl
Keyword(s):  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Fixed Dose Combination ◽  
Phase Iii ◽  
Fixed Dose ◽  
Double Blind ◽  
Efficacy Analysis ◽  
Daily Life Activities ◽  
Dose Combination ◽  
Delayed Phase

66 Background: Certain antiemesis guidelines recommend combining a 5-HT3 RA, a NK1RA and DEX for prevention of CINV associated with highly emetogenic chemotherapy (HEC) and with anthracycline + cyclophosphamide (AC)-based MEC. The objective of this analysis was to determine if using the oral fixed-dose combination NEPA prior to initiating AC-based chemotherapy resulted in no impact on daily living (NIDL) for patients. Methods: This phase III, multinational, randomized, double-blind, double-dummy, active-controlled, parallel group trial enrolled patients with solid tumors who were naïve to cytotoxics and scheduled to initiate AC-based chemotherapy. Patients received oral NEPA (netupitant 300 mg + PALO 0.5 mg) + oral DEX 12 mg on Day 1, or oral PALO 0.5 mg + oral DEX 20 mg on Day 1. The primary efficacy endpoint was Complete Response (CR: no emesis/no rescue medication) in the delayed phase (25-120 hours after chemotherapy) in cycle 1. Secondary endpoints including NIDL for patients was assessed using the Functional Living Index—Emesis (FLIE) during the first 120 hours. Results: 1,455 patients were randomized; 1,449 were included in the efficacy analysis. Significantly more patients achieved CR during the delayed phase in the NEPA arm compared with the PALO arm (76.9% vs 69.5%, respectively: p = 0.001). Significantly more patients in the NEPA arm reported NIDL via the FLIE (78.5% vs 72.1%: p = 0.005). A greater proportion of NEPA-treated patients reported no personal hardship imposed and no daily functioning affected (75.3% vs 70.5% and 77.1% vs 71.6%, respectively, as scored by the nausea domain of the FLIE; 95.2% vs 89.2% and 95.6% vs 89.2%, respectively, as scored by the vomiting domain of the FLIE). Adverse events were similar for both groups. Conclusions: NEPA significantly improved efficacy vs PALO for prevention of CINV in AC MEC and significantly more patients experienced NIDL compared to PALO. Both regimens were generally well tolerated.

Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: A randomized, double-blind study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9626-9626
Author(s):  
J. A. Boice ◽  
H. Schmoll ◽  
C. Brown ◽  
A. Taylor
Keyword(s):  
Rescue Medication ◽  
Medication Use ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Double Blind Study ◽  
Double Blind ◽  
Therapy Regimen ◽  
Control Regimen

9626 Background: Aprepitant (A) has been shown in a previous trial to be effective for prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC) in breast cancer patients receiving cyclophosphamide and anthracycline. This study assessed A in patients with a variety of tumors receiving a broad range of MEC regimens. Methods: This Phase III, randomized, gender-stratified, double-blind, trial enrolled female and male patients ≥18 years old with confirmed malignancies naïve to MEC or highly emetogenic chemotherapy and scheduled to receive a single dose of 1 or more MEC agent. Patients received A triple-therapy regimen (A 125 mg, ondansetron [O] 8 mg b.i.d., and dexamethasone [D] 12 mg on Day 1 of chemotherapy, A 80 mg q.d. on Days 2–3) or a control regimen (O 8 mg b.i.d. and D 20 mg on Day 1, and O 8 mg q12h on Days 2–3) all administered orally. Episodes of vomiting, nausea, and rescue medication use were recorded in a patient diary. Tolerability was assessed by physical and lab examinations, and adverse event (AE) reporting. Primary and key secondary efficacy endpoints were proportions of patients with No Vomiting and Complete Response (no vomiting and no rescue medication use), respectively, during the 120 hours postchemotherapy. Results: Among 848 randomized patients, 77% were female while 52, 20, 13, and 5% of patients had breast, colorectal, lung, or ovarian cancer, respectively. Significantly more patients in the A group achieved No Vomiting and Complete Response (a difference of 14.1 &12.4 percentage points vs. control, respectively). The incidences of AEs were generally similar in the aprepitant (61.9%) and control groups (66.5%). Conclusions: The aprepitant regimen provided superior efficacy over the control regimen in the treatment of CINV in a broad range of patients receiving MEC in both No Vomiting and Complete Response endpoints. Aprepitant was generally well tolerated. [Table: see text] [Table: see text]

scholarly journals Randomized, Double-Blind, Phase III Study of Fosnetupitant Versus Fosaprepitant for Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: CONSOLE

2021 ◽  
Author(s):  
Akito Hata ◽  
Isamu Okamoto ◽  
Naoki Inui ◽  
Morihito Okada ◽  
Masahiro Morise ◽  
...  
Keyword(s):  
Adverse Events ◽  
Injection Site ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Injection Site Reactions ◽  
Phase Iii Study

PURPOSE We evaluated the efficacy and safety of fosnetupitant (FosNTP) versus fosaprepitant (FosAPR) for preventing highly emetogenic chemotherapy-induced nausea and vomiting. This phase III study was the first head-to-head comparison between two different neurokinin-1 receptor antagonists in combination with palonosetron and dexamethasone. PATIENTS AND METHODS Patients scheduled to receive cisplatin-based chemotherapy were randomly assigned 1:1 to FosNTP 235 mg or FosAPR 150 mg in combination with palonosetron 0.75 mg and dexamethasone. The primary end point was overall (0-120 hours) complete response (CR; no emetic event and no rescue medication) rate, stratified by sex and age category, to show the noninferiority of FosNTP to FosAPR (noninferiority margin, –10% for the difference in the overall CR rate). RESULTS Overall, 795 patients were randomly assigned, of whom 785 received the study drug (FosNTP [N = 392] v FosAPR [N = 393]) and were evaluated for efficacy and safety. The overall CR rate was 75.2% versus 71.0%, respectively (Mantel-Haenszel common risk difference, 4.1%; 95% CI, –2.1% to 10.3%), demonstrating noninferiority of FosNTP to FosAPR. The CR rates in the acute (0-24 hours), delayed (24-120 hours), and beyond delayed (120-168 hours) phases, and at 0-168 hours were 93.9% versus 92.6%, 76.8% versus 72.8%, 86.5% versus 81.4%, and 73.2% versus 66.9%, respectively. The incidence rates of treatment-related adverse events with FosNTP versus FosAPR were 22.2% versus 25.4%, whereas adverse events or treatment-related adverse events relevant to injection site reactions were 11.0% versus 20.6% ( P < .001) and 0.3% versus 3.6% ( P < .001), respectively. CONCLUSION FosNTP demonstrated noninferiority to FosAPR, with a favorable safety profile and lower risk for injection site reactions. Thus, FosNTP is valuable in the prophylaxis of acute, delayed, and beyond delayed chemotherapy-induced nausea and vomiting.

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