Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of CINV in Breast Cancer

April 23, 2023 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

Efficacy and Safety of Intravenous Versus Oral 5-HT3 Antagonists Combined With NK-1 Receptor Antagonists for the Prevention of Breast Cancer Chemotherapy-induced Nausea and Vomiting: a Single-center, Randomized Controlled Clinical Trial

Chemotherapy is one of the most common treatments for breast cancer, but the adverse effects can be severe enough to delay or make chemotherapy intolerable, thus affecting the efficacy of the disease. Women and younger patients are more likely to experience chemotherapy-induced nausea and vomiting (CINV) . Therefore, antiemetic drugs is a key way to reduce chemotherapy side effects, which ensures compliance, and maintain quality of life. CINV is usually induced by two pathways. The central pathway is mediated by neurokinin-1 (NK-1) receptors, where chemotherapeutic agents stimulate the secretion of substance-P (SP) from the vomiting center located in the medulla oblongata and nucleus accumbens, which binds to NK-1 receptors and induces vomiting. The peripheral pathway is mediated by 5-hydroxytryptamine 3 (5-HT3) receptors, and chemotherapy stimulates intestinal chromophores in the gastrointestinal mucosa to secrete 5-HT3, which binds to its receptors to induce vomiting.

Most guidelines currently recommend the combination of 5-HT3 receptor antagonists, NK-1 receptor antagonists, and dexamethasone for high-emetogenic-risk chemotherapy regimens. Usually 5-HT3 receptor antagonists include granisetron, ondansetron, and palonosetron. Palonosetron is a second-generation 5-HT3 receptor antagonist with stronger affinity and higher efficacy than other antagonists. The commonly used NK-1 receptor antagonists are aprepitant and fosaprepitant. Fosaprepitant is an aprepitant prodrug that can be rapidly converted to aprepitant in the body, blocking the binding of substance P to NK-1 receptors for antiemetic purposes. Clinical trial has confirmed that the overall complete response (CR) rate of palonosetron 0.75 mg combined with fosaprepitant and dexamethasone was 54.9%, with 75.9% CR in the acute phase (0-24 h after chemotherapy) and 62.3% in the delayed phase (24-72 h after chemotherapy). Another clinical trial showed an acute phase CR of 89.8% and a delayed phase CR of 90.4% for oral aprepitant combined with intravenous palonosetron 0.75 mg and dexamethasone. The data suggests that both oral and intravenous administration are effective in preventing CINV, but there are no clinical trial results for oral versus intravenous administration. Oral administration is painless, has fewer side effects, and is a safer mode of administration, but bioavailability is different and drug absorption is affected by a variety of factors; whereas intravenous injection has rapid onset of action, but there are risks of injection reactions, phlebitis, and infection. Therefore, we hope to conduct a non-inferiority study on the efficacy of oral and intravenous 5-HT3 receptor antagonists combined with NK-1 receptor antagonists through this trial, which can provide more options for patients by combining the cost and administration methods.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

1028

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Zhejiang
      • Hanzhou, Zhejiang, China
        • the Second Affiliated Hospital of Zhejiang Univercity School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female, age 18-70 years.
  • Confirmed pathology suggested primary invasive breast adenocarcinoma; Presence of adjuvant chemotherapy or neoadjuvant chemotherapy indications according to clinical guidelines.
  • No other malignant tumor or other chemotherapy
  • No prior treatment for present breast cancer onset
  • ECOG physical status score 0 to 1
  • Hematological examination before treatment should meet: white blood cell count (WBC) ≥ 4.0×10^9/L, neutrophil count (ANC) ≥ 1.5×10^9/L, platelet count (PLT) ≥ 100×10^9/L; hemoglobin (Hb) ≥ 90g/L; AST (sGOT), ALT (sGPT) ≤ 1.5 times the normal value upper limit, creatinine ≤ 1.5 times the upper limit of normal value, total bilirubin ≤ 1.5 times the upper limit of normal value.
  • No serious impairment of heart, liver, kidney and other important organ functions.

Exclusion Criteria:

  • Unwilling or unable to use an acceptable method of contraception for up to and including 8 weeks after the final dose of the test drug.
  • Women during pregnancy and breastfeeding after pregnancy.
  • Women with proven distant metastases of breast cancer.
  • Patients with proven sensory or motor nerve disease.
  • Definite cardiovascular disease, severe co-morbidity or active infection, including known HIV infection.
  • Patients who need long-term anticoagulant drugs for cardiovascular or thrombotic diseases.
  • History of other tumors.
  • Allergic to the study drug or its excipients, etc.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: oral group
patients receive oral palonosetron and aprepitant
Drug: Aprepitant
oral aprepitant capsules 125mg for D1 before chemotherapy, 80mg for D2 and D3
Drug: Palonosetron
oral palonosetron 0.5mg for D1 before chemotherapy; intravenous palonosetron 0.25mg for D1 before chemotherapy;
Active Comparator: intravenous group
patients receive intravenous palonosetron and fosaprepitant
Drug: Palonosetron
oral palonosetron 0.5mg for D1 before chemotherapy; intravenous palonosetron 0.25mg for D1 before chemotherapy;
Drug: Fosaprepitant
intravenous fosaprepitant 150mg for D1 before chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
complete response
Time Frame: 0-72 hour after chemotherapy
No vomiting or additional antiemetic medication throughout the post-chemotherapy period (0-72 hours)
0-72 hour after chemotherapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
delayed phase complete response
Time Frame: 24-72 hour after chemotherapy
Delayed phase (24-72 hours after chemotherapy) without vomiting or additional antiemetic medication use
24-72 hour after chemotherapy
acute phase complete response
Time Frame: 0-24 hour after chemotherapy
Acute phase (0-24 hours after chemotherapy) without vomiting or additional antiemetic medication use
0-24 hour after chemotherapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2023

Primary Completion (Anticipated)

July 1, 2028

Study Completion (Anticipated)

July 1, 2029

Study Registration Dates

First Submitted

April 23, 2023

First Submitted That Met QC Criteria

April 23, 2023

First Posted (Actual)

May 3, 2023

Study Record Updates

Last Update Posted (Actual)

May 3, 2023

Last Update Submitted That Met QC Criteria

April 23, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-0277

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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