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

NCT ID: NCT05841849

Last Updated: 2023-05-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 1028 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-31
• Study Completion Date: 2029-07-31

Brief Summary

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.

Conditions

Breast Cancer; Chemotherapy-induced Nausea and Vomiting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

oral group

patients receive oral palonosetron and aprepitant

Group Type: EXPERIMENTAL

Aprepitant

Intervention Type: DRUG

oral aprepitant capsules 125mg for D1 before chemotherapy, 80mg for D2 and D3

Palonosetron

Intervention Type: DRUG

oral palonosetron 0.5mg for D1 before chemotherapy; intravenous palonosetron 0.25mg for D1 before chemotherapy;

intravenous group

patients receive intravenous palonosetron and fosaprepitant

Group Type: ACTIVE_COMPARATOR

Palonosetron

Intervention Type: DRUG

oral palonosetron 0.5mg for D1 before chemotherapy; intravenous palonosetron 0.25mg for D1 before chemotherapy;

Fosaprepitant

Intervention Type: DRUG

intravenous fosaprepitant 150mg for D1 before chemotherapy

Interventions

Aprepitant

oral aprepitant capsules 125mg for D1 before chemotherapy, 80mg for D2 and D3

Intervention Type: DRUG

Palonosetron

oral palonosetron 0.5mg for D1 before chemotherapy; intravenous palonosetron 0.25mg for D1 before chemotherapy;

Intervention Type: DRUG

Fosaprepitant

intravenous fosaprepitant 150mg for D1 before chemotherapy

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

the Second Affiliated Hospital of Zhejiang Univercity School of Medicine

Hanzhou, Zhejiang, China

Countries

China

Central Contacts

Wei Tian, doctor

Role: CONTACT

denyiweit@zju.edu.cn

+86 13777825246

References

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Reference Type: BACKGROUND

PMID: 27050207 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Other Identifiers

2023-0277

Identifier Type: -

Identifier Source: org_study_id