The Efficacy and Safety of Fosrolapitant and Palonosetron Hydrochloride for Injection in Preventing Nausea and Vomiting Caused by Multi-cycle Immunotherapy and Chemotherapy in Patients With Esophageal Cancer and Lung Cancer

Zhejiang University

Status and phase: Enrolling; Phase 2

Conditions: Esophagus Cancer; Lung Cancer

Treatments: Drug: For injection, fosapirtan dimeglumine combined with palonosetron hydrochloride and dexamethasone acetate; Drug: Fosrolapitant and Palonosetron Hydrochloride for Injection combined with dexamethasone acetate

Study type: Interventional

Funder types: Other

Identifiers

NCT07617246

FEAL

Details and patient eligibility

About

This study was a randomized, parallel, cohort study to evaluate the efficacy and safety of Fosrolapitant and Palonosetron Hydrochloride for Injection in preventing nausea and vomiting caused by multi-cycle immunotherapy and chemotherapy in patients with esophageal cancer and lung cancer. A total of 120 subjects are planned to be enrolled, with 60 in each cohort. 40% of the subjects will undergo an interim analysis upon completion of the study.

The trial consists of a screening period, a treatment period and a safety follow-up period. Drug treatment was administered in accordance with the trial protocol, and then the corresponding follow-up and examination were completed in accordance with the trial process table. During the research period, if the researcher assesses that the subjects indeed need to use remedial antiemetic drugs, remedial treatment can be carried out based on clinical practice. The specific types, usage, dosage and frequency of the drugs are determined by the researcher.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥18 years old, gender not limited;

• Histologically or cytologically confirmed untreated locally advanced/metastatic esophageal cancer and lung cancer;

• Has not received any chemotherapy drugs in the past (anti-tumor drugs are not used for cancer treatment);

• Plan to receive at least 4 cycles of chemotherapy combined with immunotherapy based on cisplatin and carboplatin;

• Expected survival period ≥3 months;

• Eastern Cooperative Oncology Group (ECOG) Physical Condition score: 0 or 1 point;

• Good organ function, meeting the following criteria:

  1. Neutrophil count ≥1.5×109/L;
  2. Hemoglobin ≥ 90g/L;
  3. Platelet count ≥ 100×109/L;
  4. Total bilirubin ≤1.5×ULN In patients without known liver metastases, aspartate aminotransferase ≤2.5×ULN and/or alanine aminotransferase ≤2.5×ULN (for patients with liver metastases, it can be relaxed to ≤5×ULN);

  f: Serum creatinine ≤1.5×ULN or creatinine clearance rate ≥ 50ml/min; g: Electrocardiogram: QTc≤450ms (for males), QTc≤470ms (for females); h: Cardiac color Doppler ultrasound: LVEF (left ventricular ejection fraction) ≥50%;

• Fertile female subjects and male subjects whose partners are fertile women need to adopt an effective contraceptive measure from the time of signing the informed consent form until 6 months after the last administration. Female subjects with fertility must have a negative blood pregnancy test within 72 hours before randomization. And it must be non-lactation period;

• Clearly understand and voluntarily participate in this research, and sign the informed consent form by oneself.

Exclusion criteria

• Abdominal (including the diaphragmatic plane and below) or pelvic radiotherapy was received within 7 days prior to randomization, or is planned to be received within 1 to 8 days of treatment;
• It is planned to administer chemotherapy drugs with a high risk of vomiting within 2 to 8 days after platinum infusion.
• Plan to receive chemotherapy regimens including common paclitaxel (using castor oil as the solvent);
• Take drugs with potential antiemetic effects within 2 days before randomization: The first-generation 5-HT3 receptor antagonists (such as ondansetron), phenthiazide drugs (such as prochlorazine), butanylbenzene drugs (such as haloperidol), benzamides (such as metoclopramide), domperidone, cannabinoids, traditional Chinese medicines with potential antiemetic effects, scopolamine, cyclezine, etc.
• Start treatment with benzodiazepines or opioid preparations within 2 days before randomization (except for triazolam, temazepam or midazolam taken alone daily);
• Subjects who began using morphine within 7 days before randomization (except those taking a stable dose);
• Within 7 days before randomization, systemic corticosteroid therapy (including but not limited to dexamethasone, hydrocortisone, methylprednisolone or prednisolone) or sedative antihistamines (such as diphenhydramine) were received (Note: Single use of steroids is allowed to prevent contrast agent allergy and local administration or inhalation), except for those who need hormone pretreatment one day before chemotherapy.
• Palonosetron was used within 14 days prior to randomization;
• Use NK-1 receptor antagonists within 28 days before randomization;
• Specific CYP3A4 substrates (terfenadine, cisapride, asemidazole) or CYP3A4 inhibitors (such as ritonavir, clarithromycin, ketoconazole or itraconazole, diltiazem, etc.) were used within 7 days before randomization. Strong CYP3A4 inducers (such as phenobarbital, rifampicin, phenytoin and carbamazepine) or specific CYP2D6 substrates (thiolidazine, pimozide) were used within 28 days before randomization;
• Vomiting and/or retching and nausea occurred within 24 hours before randomization; Subjects with symptomatic brain metastases;
• Accompanied by poorly controlled serous cavity effusion, including pleural effusion, ascites, and pericardial effusion (those that have been controlled after treatment and remained stable for ≥2 weeks can be included);
• Having severe cardiovascular diseases within 3 months prior to randomization, including but not limited to acute myocardial infarction, unstable angina pectoris, significant valvular or pericardial disease, history of ventricular tachycardia, symptomatic chronic heart failure (New York Heart Association [NYHA] grades II to IV), and history of severe cardiac conduction abnormalities (such as torus cuspidata ventricular tachycardia);
• Poorly controlled hypertension (two consecutive resting systolic blood pressures ≥160mmHg and/or diastolic blood pressures ≥100mmHg) before randomization;
• Those with combined active hepatitis B (HBV DNA≥2000 IU/mL or 104 copies/mL), active hepatitis C (HCV-Ab positive and HCV-RNA≥ upper limit of normal value), acquired immune deficiency syndrome (AIDS) or positive HIV test, and positive syphilis test;
• Concomitant diseases that prevent dexamethasone from being taken, such as active infections (like pneumonia) or any uncontrolled diseases (such as diabetic ketoacidosis, gastrointestinal obstruction, etc.);
• Known contraindications of NK-1 receptor antagonists, 5-HT3 receptor antagonists or dexamethasone;
• Having participated in other clinical trials within 30 days prior to randomization (based on the use of the study drug);
• Subjects who the researchers consider to have other circumstances that make them unsuitable to participate in this study.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups, including a placebo group

1

Experimental group

Description:

Fosrolapitant and Palonosetron Hydrochloride for Injection combined with dexamethasone acetate

Treatment:

Drug: Fosrolapitant and Palonosetron Hydrochloride for Injection combined with dexamethasone acetate

2

Placebo Comparator group

Description:

For injection, fosapirtan dimeglumine combined with palonosetron hydrochloride and dexamethasone acetate

Treatment:

Drug: For injection, fosapirtan dimeglumine combined with palonosetron hydrochloride and dexamethasone acetate