A Cohort Study on the Prevention of Nausea and Vomiting Induced by Concurrent Chemoradiotherapy for Lung Cancer Using Rolapitant and Palonosetron

Official title

A Cohort Study of the Combination Regimen Based on Rolapitant and Palonosetron for the Prevention of Nausea and Vomiting Induced by Concurrent Chemoradiotherapy in Lung Cancer Patients

Overview

This study aims to evaluate the efficacy and safety of a combination regimen based on Rolapitant Palonosetron injection for preventing nausea and vomiting induced by concurrent chemoradiotherapy in lung cancer patients. It will also analyze the differences in preventive efficacy between two combination regimens, filling the gap in antiemetic data for radiotherapy combined with moderately to highly emetogenic chemotherapy. This research will provide evidence for optimizing antiemetic strategies in patients undergoing concurrent chemoradiotherapy.

Detailed description

Rolapitant Palonosetron is a combination formulation containing 218 mg of foslora-palanitapentan and 0.25 mg of palo-nexon. It integrates an NK1 receptor antagonist (rolapitant) with a second-generation 5-HT3 receptor antagonist (palonosetron). This dual mechanism simultaneously blocks 5-HT3 and NK-1 pathways, inhibiting the vomiting reflex through dual pathways to provide long-lasting antiemetic efficacy.

The injectable formulation of Rolapitant Palonosetron exhibits an exceptionally long half-life of 188 hours. The PROFIT study demonstrated that a single injection per cycle provides coverage across the acute, delayed, and ultra-delayed phases of CINV, offering sustained protection for up to 8 days. It achieved a complete response (CR) rate exceeding 90% in both the acute and ultra-delayed phases across two consecutive chemotherapy cycles.

Existing studies predominantly focus on chemotherapy-only populations, with limited prospective data for concurrent chemoradiotherapy patients. The efficacy of currently used triple/quadruple antiemetic regimens in this setting requires further investigation, particularly the novel prophylactic strategy combining Rolapitant Palonosetron with dexamethasone ± olanzapine. Against this backdrop, this study aims to evaluate the efficacy and safety of a combination regimen based on Rolapitant Palonosetron injection for preventing nausea and vomiting induced by concurrent chemoradiotherapy in lung cancer patients. It will also analyze the differences in preventive efficacy between two combination regimens, filling the gap in antiemetic data for radiotherapy combined with moderately to highly emetogenic chemotherapy. This research will provide evidence for optimizing antiemetic strategies in patients undergoing concurrent chemoradiotherapy.

Interventions

• Drug Rolapitant Palonosetron
  • D1: 1 hour prior to chemotherapy administration: Rolapitant Palonosetron(Rolapitant 218mg and Palonosetron Medipentide 0.25mg), IV; 30 minutes prior to chemotherapy；
• Drug Dexamethasone
  DEX 12 mg, PO, QD; D2-D4: DEX 3.75 mg, PO, BID;
• Drug Olanzapine
  Olanzapine: 5 mg orally, QN, starting the night before the first chemotherapy session and continuing until 2 days after chemotherapy completion;

Primary outcome measures

• Complete Remission (CR) Rate [Time frame: within 6 weeks]

Secondary outcome measures (3)

• Complete Protection (CP) Rate [Time frame: within 6 weeks]
• Total Control (TC) Rate [Time frame: within 6 weeks]
• Incidence of adverse events (AE) [Time frame: within 6 weeks]

Eligibility criteria

Inclusion criteria

• Age ≥18 years, no gender restrictions;
• Histopathologically or cytologically confirmed lung cancer;
• Planned to receive concurrent chemoradiotherapy for at least 6 weeks, with radiotherapy administered in conventional fractions (2.0-2.2 Gy/fraction, 5 fractions/week, total dose 60-66 Gy); chemotherapy regimen includes highly emetogenic agents (e.g., cisplatin ≥60 mg/m²) ;
• ECOG Performance Status score: 0-1;
• Expected survival >12 weeks;
• Adequate organ and bone marrow function;
• Willingness to complete daily nausea/vomiting logs and scale assessments.

Exclusion criteria

• Patients with imaging-confirmed brain metastases accompanied by symptoms of increased intracranial pressure (e.g., headache, vomiting, papilledema) or objective evidence of elevated intracranial pressure.
• Patients with a documented history of severe hypersensitivity to the active ingredient or excipients of the drug.
• Known contraindications to NK-1 receptor antagonists, 5-HT3 receptor antagonists, dexamethasone, or olanzapine;
• Vomiting symptoms (≥1 episode/day) or VAS score ≥30 mm within 7 days prior to first administration;
• Use of medications with potential antiemetic effects within 2 days prior to first dose: first-generation 5-HT3 receptor antagonists (e.g., ondansetron), phenothiazines (e.g., prochlorperazine), butyrophenones (e.g., haloperidol), benzamides (e.g., metoclopramide), domperidone, cannabinoids, traditional Chinese medicines with potential antiemetic effects, scopolamine, secloperazine, etc.;
• Presence of conditions affecting vomiting assessment, such as gastrointestinal obstruction, gastroparesis, or intestinal obstruction;
• History of epilepsy or current use of antiepileptic drugs;
• Pregnant or lactating women;
• History of severe psychiatric disorders, substance abuse, alcoholism, or drug addiction;
• Currently participating in another interventional clinical trial, or having received treatment with another investigational drug or device within 4 weeks prior to the first dose (subjects who failed screening for another clinical trial may be included in this study);
• Presence of any other factors deemed by the investigator to increase study risk, compromise patient compliance with the protocol, or affect the patient's ability to complete the trial, such as physiological or psychological conditions;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07442890 · HR20013-HN-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗