Preventing opioid-related nausea and vomiting with naldemedine in people with cancer

Prophylactic Use of Naldemedine on Opioid-Induced Nausea and Vomiting in Patients With Cancer: A Multicenter, Randomized, Placebo-Controlled, Double-Blind Study

This study will test whether taking naldemedine when starting opioid pain medicines can prevent nausea and vomiting in adults with cancer.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: International University of Health and Welfare (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Narita)
• Trial ID: NCT07038551 on ClinicalTrials.gov

What this trial studies

Adults with cancer who are about to start regular opioid analgesics will be enrolled and given either naldemedine or a matching placebo while they begin their opioid regimen. Participants must be able to take oral medication and keep a symptom diary for at least seven days to record nausea, vomiting, and bowel function. Patients who used opioids in the prior 28 days, who already take naldemedine, or who have moderate-to-severe nausea or vomiting are excluded. The trial compares symptom frequency and severity between the naldemedine and placebo groups during the initial opioid treatment period.

Who should consider this trial

Good fit: Adults with cancer who are about to begin regular opioid analgesics (such as tramadol, morphine, oxycodone, or hydromorphone), can take oral medications, and can complete a short symptom diary are the ideal candidates.

Not a fit: Patients who recently used opioids, are already taking naldemedine, have moderate-to-severe nausea or vomiting at baseline, cannot take oral medications, or cannot keep the required diary are unlikely to benefit from this prevention approach.

Why it matters

Potential benefit: If successful, prophylactic naldemedine could reduce nausea and vomiting when patients start or increase opioid pain medicines, improving comfort and adherence to pain control.

How similar studies have performed: Naldemedine and similar peripherally acting opioid antagonists have established benefit for opioid-induced constipation, but using naldemedine specifically to prevent opioid-induced nausea and vomiting is relatively untested.

Eligibility criteria

Inclusion Criteria:

1. Patients who can be expected to initiate regular administration of opioid analgesics (tramadol, morphine, oxycodone, hydromorphone) for cancer pain and continue for 7 days or more.
2. Patients who are 18 years of age or older at the time of obtaining consent
3. Patients who can take oral medications, food, and beverages
4. Patients who are considered capable of self-recording in the patient's diary (proxy recording in the patient's diary is acceptable if the patients are capable of self-assessment).
5. Patients who are not expected to have a rapid change in their condition during the study period.
6. Patients who can obtain written consent to participate in the study of their own will

Exclusion Criteria:

1. Patients who have used opioid analgesics within 28 days prior to the date of consent
2. Patients who have taken or are currently taking naldemedine
3. Patients who have nausea and vomiting of CTCAE grade 2 or higher at the time of obtaining consent
4. Patients who have taken the following antiemetic drugs within 7 days prior to the date of consent Metoclopramide, domperidone, H1 histamine receptor antagonists, phenothiazine antipsychotics (chlorpromazine, levomepromazine, prochlorperazine), haloperidol, atypical antipsychotics (perospirone, risperidone, olanzapine), serotonin 5HT3 receptor antagonists (ondansetron, granisetron, ramosetron, palonosetron), corticosteroids (dexamethasone), scopolamine hydrobromide, NK1 receptor antagonists (aprepitant, fosaprepitant, fosnetupitant)
5. Patients who have received cancer chemotherapy that is certain to affect nausea and vomiting within 14 days prior to the initial enrollment date, or who are scheduled to receive such therapy within the study period. Cancer chemotherapy that is certain to affect nausea and vomiting will be defined as follows:

   ① Initial administration of a therapeutic regimen containing irinotecan (CPT-11)

   ② Other cancer chemotherapy that is considered certain to affect nausea and vomiting.

   However, the following cases may be considered as not affecting defecation
   * Chemotherapy with the same regimen as the previous course or chemotherapy with the same drug and dose, and there was no moderate or greater nausea and vomiting (CTCAE v5.0 Grade 2 or higher) during the previous course or previous chemotherapy.
   * Patients who have received oral anticancer agents (e.g. TS-1) daily and have not had moderate or severe nausea and vomiting (CTCAE v5.0 Grade 2 or higher) for at least 1 week from the start of oral chemotherapy to the start of study drug.
6. Pregnant or lactating patients
7. Patients with suspected hypersensitivity to opioid receptor antagonists such as naldemedine, naltrexone, methylnaltrexone, and naloxone
8. Patients with contraindications listed in the package inserts for naldemedine and opioid analgesics (tramadol, morphine, oxycodone, hydromorphone)
9. Patients participating or scheduled to participate in clinical trials or other interventional studies
10. Patients with gastrointestinal obstruction or suspected gastrointestinal obstruction, or patients with a history of gastrointestinal obstruction and a high risk of recurrence
11. Patients who have undergone surgery or treatment (e.g., nerve block) that affects gastrointestinal function, or radiation therapy to the head, abdomen, or pelvis within 14 days prior to the date of consent acquisition, or patients who are scheduled to undergo such treatment during the observation period
12. Patients with medically significant cardiovascular, respiratory, hepatic, or renal dysfunction based on history, clinical laboratory values, electrocardiogram, or physical examination, who are judged inappropriate to participate in the study
13. Patients with symptomatic intracranial conditions (such as brain metastases or leptomeningeal disease)
14. Patients with suspected dysfunction or impairment of the blood-brain barrier
15. Patients for whom it is difficult to explain the contents of the study or obtain consent due to cognitive impairment or psychiatric illness
16. Patients who are judged by the principal investigator or sub-investigator to be inappropriate to participate in this study based on other concomitant therapies or medical findings

Where this trial is running

Narita

• International university of health and welfare Narita hospital — Narita, Japan (RECRUITING)

Study contacts

• Study coordinator: Yo Ishihara

Conditions: Opioid-Induced Constipation, Nausea, Vomiting, Constipation