Oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting: a study protocol for a pilot and definitive randomised double-blind placebo-controlled trial (CannabisCINV)

IntroductionChemotherapy-induced nausea and vomiting (CINV) remains an important issue for patients receiving chemotherapy despite guideline-consistent antiemetic therapy. Trials using delta-9-tetrahydrocannabinol-rich (THC) products demonstrate limited antiemetic effect, significant adverse events and flawed study design. Trials using cannabidiol-rich (CBD) products demonstrate improved efficacy and psychological adverse event profile. No definitive trials have been conducted to support the use of cannabinoids for this indication, nor has the potential economic impact of incorporating such regimens into the Australian healthcare system been established. CannabisCINV aims to assess the efficacy, safety and cost-effectiveness of adding TN-TC11M, an oral THC/CBD extract to guideline-consistent antiemetics in the secondary prevention of CINV.Methods and analysisThe current multicentre, 1:1 randomised cross-over, placebo-controlled pilot study will recruit 80 adult patients with any malignancy, experiencing CINV during moderate to highly emetogenic chemotherapy despite guideline-consistent antiemetics. Patients receive oral TN-TC11M (THC 2.5mg/CBD 2.5 mg) capsules or placebo capsules three times a day on day −1 to day 5 of cycle A of chemotherapy, followed by the alternative drug regimen during cycle B of chemotherapy and the preferred drug regimen during cycle C. The primary endpoint is the proportion of subjects attaining a complete response to CINV. Secondary and tertiary endpoints include regimen tolerability, impact on quality of life and health system resource use. The primary assessment tool is patient diaries, which are filled from day −1 to day 5. A subsequent randomised placebo-controlled parallel phase III trial will recruit a further 250 patients.Ethics and disseminationThe protocol was approved by ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences.Drug supplyTilray.Protocol version2.0, 9 June 2017.Trial registration numberANZCTR12616001036404; Pre-results.

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The Oral Neurokinin-1 Antagonist Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Multinational, Randomized, Double-Blind, Placebo-Controlled Trial in Patients Receiving High-Dose Cisplatin—The Aprepitant Protocol 052 Study Group

Journal of Clinical Oncology ◽

10.1200/jco.2003.01.095 ◽

2003 ◽

Vol 21 (22) ◽

pp. 4112-4119 ◽

Cited By ~ 538

Author(s):

Paul J. Hesketh ◽

Steven M. Grunberg ◽

Richard J. Gralla ◽

David G. Warr ◽

Fausto Roila ◽

...

Keyword(s):

Standard Therapy ◽

Therapy Group ◽

Rescue Therapy ◽

Controlled Trial ◽

Complete Response ◽

Nausea And Vomiting ◽

Phase Iii ◽

High Dose ◽

Double Blind ◽

Double Blind Placebo

Purpose: In early clinical trials with patients receiving highly emetogenic chemotherapy, the neurokinin antagonist aprepitant significantly enhanced the efficacy of a standard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid. This multicenter, randomized, double-blind, placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus standard therapy in the prevention of chemotherapy-induced nausea and vomiting (CINV). Patients and Methods: Patients receiving cisplatin ≥ 70 mg/m2 for the first time were given either standard therapy (ondansetron and dexamethasone on day 1; dexamethasone on days 2 to 4) or an aprepitant regimen (aprepitant plus ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2 to 3; dexamethasone on day 4). Patients recorded nausea and vomiting episodes in a diary. The primary end point was complete response (no emesis and no rescue therapy) on days 1 to 5 postcisplatin, analyzed by a modified intent-to-treat approach. Treatment comparisons were made using logistic regression models. Tolerability was assessed by reported adverse events and physical and laboratory assessments. Results: The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group (72.7% [n = 260] v 52.3% in the standard therapy group [n = 260]), as were the percentages on day 1, and especially on days 2 to 5 (P < .001 for all three comparisons). Conclusion: Compared with standard dual therapy, addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy.

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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.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.29_suppl.176 ◽

2015 ◽

Vol 33 (29_suppl) ◽

pp. 176-176 ◽

Cited By ~ 5

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.68 ◽

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]

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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)

Journal of Clinical Oncology ◽

10.1200/jco.2017.72.2538 ◽

2017 ◽

Vol 35 (31) ◽

pp. 3558-3565 ◽

Cited By ~ 10

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.

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The addition of omeprazole to ondansetron for treating chemotherapy-induced nausea and vomiting in pediatric cancer patients

Paediatrica Indonesiana ◽

10.14238/pi1.1.2018.42-7 ◽

2018 ◽

Vol 1 (1) ◽

pp. 42

Author(s):

Perjuangan Dapot Hamonangan Simbolon ◽

Selvi Nafianti ◽

Pertin Sianturi ◽

Bidasari Lubis ◽

Aznan Lelo

Keyword(s):

Placebo Group ◽

Cancer Patients ◽

Pediatric Cancer ◽

Controlled Trial ◽

Complete Response ◽

Nausea And Vomiting ◽

Chi Square ◽

Double Blind ◽

Significant Difference ◽

Pediatric Cancer Patients

Background Chemotherapy-induced nausea and vomiting are some of the most disturbing side effects in pediatric cancer patients. The standard recommendation is the use of 5-hydroxytryptamine 3 receptor antagonist, such as ondansetron, to treat these symptoms. Despite this treatment, more than 50% of patients still experience nausea and vomiting.Objective To evaluate the effect of the addition of omeprazole to ondansetron in the treatment of chemotherapy-induced nausea and vomiting.Methods A double-blind, randomized, controlled trial was conducted at Haji Adam Malik Hospital, Medan, North Sumatera, from March to May 2016. Subjects were children aged 1 to 18 years, diagnosed with cancer, and who received intravenous chemotherapy. Patients were randomized to receive either a single dose of ondansetron (0.5 mg/kg) plus placebo or ondansetron (0.5 mg/kg) plus omeprazole (0.5 mg/kg). The severity of nausea and vomiting were measured using the Rhodes index of nausea, vomiting, and retching during the 24 hours after initiation of emetogenic chemotherapy. The primary outcome of efficacy was the proportion of patients who achieved complete response (lack of nausea/vomiting). Statistical analysis was performed by Chi-square and Fischer’s exact tests.Results Seventy eligible pediatric patients were randomized into two groups: 32 subjects in the ondansetron + placebo group and 38 others in the ondansetron + omeprazole group. The therapy failed in 50% (16/32) of the ondansetron + placebo group and 18.4% (7/38) of the ondansetron + omeprazole group. There was a significant difference in the clinical response between groups (P=0.01).Conclusion The addition of omeprazole to ondansetron for the treatment of chemotherapy-induced nausea and vomiting is more effective than administration of ondansetron alone.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9626 ◽

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]

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Effects of aprepitant /dexamethasone versus mirtazapine/dexamethasone on postoperative nausea and vomiting after laparoscopic sleeve gastrectomy: a randomized controlled trial

10.21203/rs.3.rs-107678/v1 ◽

2020 ◽

Author(s):

Tarek Ashoor ◽

Dina Y. Kassim ◽

Ahmed M. Hasseb ◽

Ibrahim M. Esmat

Keyword(s):

Sleeve Gastrectomy ◽

Laparoscopic Sleeve Gastrectomy ◽

Postoperative Nausea ◽

Controlled Trial ◽

Postoperative Nausea And Vomiting ◽

Complete Response ◽

Nausea And Vomiting ◽

Morbidly Obese ◽

Double Blind ◽

Patient’S Satisfaction

Abstract Background Co-administration of different antiemetics proved to decrease postoperative nausea and vomiting (PONV) following laparoscopic sleeve gastrectomy (LSG). The investigators compared the combination of aprepitant and dexamethasone (A/D) with the combination of mirtazapine and dexamethasone (M/D) for prevention of PONV in morbidly obese patients undergoing LSG. Methods Ninety patients scheduled for LSG were assigned to receive a single preoperative dose of dexamethasone 8 mg IVI (D group), and in addition to oral aprepitant 80 mg (A/D group) or oral mirtazapine 30 mg (M/D group) in a randomized, double-blind trial. Assessment of PONV was done 0–2 h (early) and 2–24 hours (late). Patients’ level of sedation, satisfaction and postoperative pain were also assessed. Results A/D and M/D groups were superior to D group for complete response 0–24 h after surgery (79.3% for A/D group, 78.6% for M/D group and 20.7% for D group). D group was inferior to A/D and M/D groups regarding collective PONV and use of rescue antiemetics (P < 0.001) 0–24 h after surgery. The peak nausea scores 2–24 h were significantly lower in both A/D and M/D groups vs. D group (P = 0.005). Patients in the M/D group showed higher sedation scores while those in A/D groups showed lower pain scores and less analgesic requirements. A/D and M/D groups were superior to D group regarding the patient’s satisfaction score. Conclusion A/D and M/D combinations were superior to D alone regarding the proportion of patients exhibiting a complete response in preventing PONV associated with LSG. Trial Registration: Clinical Trials. gov Identifier: NCT04013386/ prospectively registered: 09/07/2019, http://www.Clinical Trial.gov

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Can adjuvant homeopathy improve the control of post-chemotherapy emesis in breast cancer patients? Results of a randomized placebo-controlled trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e20566 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e20566-e20566

Author(s):

I. L. Ray-Coquard ◽

J. Provençal ◽

A. C. Hardy-Bessard ◽

T. Bachelot ◽

D. Coeffic ◽

...

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Primary Endpoint ◽

Controlled Trial ◽

Metastatic Breast ◽

Nausea And Vomiting ◽

Phase Iii ◽

Breast Cancer Patients ◽

Double Blind ◽

Tac Chemotherapy

e20566 Background: Homeopathy used as an adjunct in the treatment of chemotherapy (CT)-induced emesis has rarely been evaluated. Methods: Patients with non-metastatic breast cancer treated with 6 courses of FAC 50, FEC 100 or TAC chemotherapy were randomized to Cocculus/nux vomica/tabacum/petroleum extract (Cocculine, C) or Placebo (P) in a multicentric comparative double-blind phase III study. Anti-emetic treatment was standardized (corticoids + ondansetron). Patients were evaluated after each course. The primary endpoint was nausea measured after the 1st CT course using the FLIE (Functional Living Index for Emesis) with 5-day recall. The planned sample size was 396 evaluable patients based on a minimum expected difference in mean of 0.5 ± 1.6 on a scale from 1 (a lot) to 7 (not at all) with 5% two-sided α error and 85% power. An intent-to-treat analysis was planned. Secondary evaluation criteria were: vomiting measured by the FLIE score, patient self-evaluation (EVA) and investigator recording (NCI-CTC) of nausea and vomiting intensities, and compliance. Results: From September 05 to January 08, 431 patients were randomized (217 to P and 214 to C). Patient characteristics were well balanced between groups. Median age was 53 years, 35% of the patients experienced nausea or vomiting. In total, 403 patients (93.5%) were assessable for the primary endpoint, with few nausea episodes (FLIE nausea scores after the 1st CT course were 6.02 and 6.07 for P and C, respectively) and very good compliance (81% patients complied with the protocol). Adverse events related to nausea occurred in 51% vs. 47% of the patients treated with P and C, respectively (p = 0.48). FLIE and NCI-CTC vomiting scores were similar between the 2 arms (6.91 vs. 6.88, p = 0.47, and 20% vs. 21%, p = 0.73, for P and C, respectively). Grade II-III nausea occurred in 17.6% and 15.7% of patients receiving P and C (p = 0.62). Conclusions: No benefit of homeopathy over standard treatment was noted in this study. But surprisingly we observed lower rates of nausea and vomiting measured by patients and by investigators, than in other studies using identical chemotherapy regimens. The observation and management of emesis could modify the perception and rate of such adverse events. No significant financial relationships to disclose.

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The addition of omeprazole to ondansetron for treating chemotherapy-induced nausea and vomiting in pediatric cancer patients

Paediatrica Indonesiana ◽

10.14238/pi58.1.2018.42-7 ◽

2018 ◽

Vol 58 (1) ◽

pp. 42

Author(s):

Perjuangan Dapot Hamonangan Simbolon ◽

Selvi Nafianti ◽

Pertin Sianturi ◽

Bidasari Lubis ◽

Aznan Lelo

Keyword(s):

Placebo Group ◽

Cancer Patients ◽

Pediatric Cancer ◽

Controlled Trial ◽

Complete Response ◽

Nausea And Vomiting ◽

Chi Square ◽

Double Blind ◽

Significant Difference ◽

Pediatric Cancer Patients

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A randomized, double-blind, multicenter, phase III study of fosnetupitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving doxorubicin-cyclophosphamide/epirubicin-cyclophosphamide (AC/EC) based highly emetogenic chemotherapy: CONSOLE-BC.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.12094 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 12094-12094

Author(s):

Junji Tsurutani ◽

Kazuo Matsuura ◽

Kenichi Inoue ◽

Yuko Tanabe ◽

Tetsuhiko Taira ◽

...

Keyword(s):

Primary Endpoint ◽

Study Drug ◽

Complete Response ◽

Nausea And Vomiting ◽

Phase Iii ◽

Pivotal Phase ◽

Double Blind ◽

History Of ◽

Neurokinin 1 ◽

To Receive

12094 Background: Fosnetupitant (FN) is a phosphorylated pro-drug of netupitant that has high binding affinity and selectivity for the neurokinin 1 receptor and a long half-life of 70 h. Recent studies have reported that fosaprepitant (FA) has a risk for developing injection site reactions (ISRs) in patients with breast cancer who receive doxorubicin-cyclophosphamide/epirubicin-cyclophosphamide (AC/EC)-based treatments. Previous studies have shown that FN may have a low risk of ISRs and could potentially address this unmet medical need. The present study (JapicCTI-194691) was intended to evaluate the safety profile, including ISRs, of FN in patients receiving AC/EC treatment. For exploratory purposes, we set the FA group as the exploratory arm. A separate pivotal phase 3 study (JapicCTI-194611) was conducted to verify the efficacy and safety of FN compared with FA in patients receiving cisplatin-based chemotherapy. Methods: Patients scheduled to receive AC/EC were randomly assigned 1:1 to receive FN 235 mg or FA 150 mg in a double-blind manner, in combination with intravenous palonosetron (PALO) 0.75 mg and dexamethasone (DEX) 9.9 mg on day 1. The stratification factors were age class ( < 55 years vs. ≥55 years) and site. The primary endpoint was the incidence of treatment-related adverse events (TRAEs) of FN. In addition, the ISRs were investigated as secondary endpoints. Efficacy outcomes were also evaluated as secondary endpoint. Results: Between April 2019 and March 2020, total 102 patients were enrolled in the study. Fifty-two patients were randomized to the FN group and 50 to the FA group, and all of them were treated with the study drug and evaluated for safety. The baseline characteristics were generally balanced, except for the history of motion sickness (54.9% vs. 44.9%) and non-smokers (78.4% vs. 63.3%) in the FN and FA groups, respectively, which are considered as risk factors for chemotherapy-induced nausea and vomiting. The primary endpoint, the incidence of TRAEs was 21.2% (n = 11) (95% CI 11.1% – 34.7%) in the FN group, which was similar to that in the FA group [22.0% (n = 11) (95% CI 11.5% - 36.0%) ]. Any cause or treatment-related ISRs were observed in 5.8% (n = 3) and 0% (n = 0), respectively, in the FN group and 26.0% (n = 13) and 10.0% (n = 5), respectively, in the FA group. The overall (0–120 h) complete response (no emetic event and no rescue medication) rate standardized by age category was 45.9% (n = 23) in the FN group and 51.3% (n = 25) in the FA group. Conclusions: The safety of FN in combination with PALO and DEX was favorable. Risk of ISR by FN was quite low in the AC/EC setting. Clinical trial information: JapicCTI-194691.

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