Safety and Antiemetic Efficacy of Akynzeo Plus Dexamethasone During Radiotherapy and Concomitant Weekly Cisplatin
NCT ID: NCT03668639
Last Updated: 2021-12-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
PHASE2/PHASE3
80 participants
INTERVENTIONAL
2018-09-05
2023-04-15
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
From a previous clinical trial (GAND-emesis trial) we know that patients receiving radiotherapy and concomitant weekly cisplatin 40 mg/m2 are better protected against nausea and vomiting when a triplet antiemetic prophylaxis (neurokinin-1 receptor antagonist, serotonin receptor antagonist, and corticosteroid) is applied.
In the Akynzeo phase III clinical trials, Akynzeo was administered every three weeks. The neurokinin-1 receptor antagonist, netupitant, has a long plasma half-life (approx. 90 hours), and theoretically the drug could accumulate when administered on a weekly basis.
The DANGER-emesis trial is designed to collect safety and efficacy data in patients receiving Akynzeo weekly as antiemetic prophylaxis in combination with dexamethasone in patients treated for cervical cancer with radiotherapy and concomitant weekly cisplatin 40 mg/m2.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
SUPPORTIVE_CARE
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Akynzeo plus dexamethasone
Akynzeo (capsule 300mg/0.5mg) Day 1 plus dexamethasone 12 mg Day 1, 8 mg Day 2-3, and 4 mg Day 4 to be administered weekly for five weeks.
Akynzeo
Weekly administration of akynzeo for five weeks.
Dexamethasone
Weekly administration of dexamethasone 12 mg Day 1, 8 mg Day 2-3, and 4 mg Day 4 for five weeks.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Akynzeo
Weekly administration of akynzeo for five weeks.
Dexamethasone
Weekly administration of dexamethasone 12 mg Day 1, 8 mg Day 2-3, and 4 mg Day 4 for five weeks.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. The patient understands the nature and purpose of this study and the study procedures and has signed informed consent.
3. The patient is aged ≥ 18 years.
4. The patient must be both chemo- and radiotherapy (RT) naïve. NB: previously low voltage RT or electron RT for non-melanoma skin cancers is allowed.
5. The patient is scheduled to receive fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2 for at least five weeks.
6. Brachy therapy is scheduled to be initiated after the third cycle of weekly cisplatin, and preferentially after the fifth week of treatment.
7. Chemotherapy with an emetic risk potential of minimal or mild (up to 30%) is allowed on days 1-4 (see ref. 14).
8. The patient has a WHO Performance Status of ≤ 2.
9. Hematologic and metabolic status must be adequate for receiving weekly cisplatin in a dose of ≥ 40 mg/m2, and meet the following criteria:
* Total neutrophils ≥ 1500/mm3 (Standard units : ≥1.5 x 109/L)
* Platelets ≥ 100,000/mm3 (Standard units: ≥100.0 x 109/L)
* Bilirubin ≤ 1.5 x ULN (Upper Limits of Normal)
* Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 x ULN
* GFR ≥ 50 ml/min
10. The patient is able to read, understand, and complete questionnaires and daily components of the Patient Diary for each study cycle.
11. For patients of childbearing potential, urine human chorionic gonadotropin (hCG) (urine dipstick pregnancy test) or blood hCG results must be negative at screening, and these patients must agree to one of the following methods of contraception:
* Hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release).
* Male partner who is sterile prior to the patient's entry into the study and is the sole sexual partner for that patient.
* Complete abstinence from intercourse for two weeks before study entry and throughout the study period plus a period after the trial to account for elimination of the drug (minimum of eight days). Abstinence is only an acceptable contraception form, when it reflects the usual and preferred lifestyle of the patient.
Exclusion Criteria
2. The patient is pregnant or lactating.
3. The patient has experienced emesis (i.e., vomiting and/or retching) or clinically significant nausea (defined as nausea graded as moderate or severe) in the 24 hours preceding the first dose of study medication.
4. The patient has a history active peptic ulcer disease, gastrointestinal obstruction, gastrointestinal carcinoma, increased intracranial pressure, hypercalcemia, or any uncontrolled medical condition (other than malignancy) which in the opinion of the Investigator may confound the results of the study, represent another potential etiology for emesis and nausea (other than CINV/RINV) or pose an unwarranted risk to the patient.
5. The patient has a known hypersensitivity or contraindication to palonosetron, another 5-HT3 receptor antagonist, dexamethasone, or netupitant.
6. The patient has previously received an NK1 receptor antagonist.
7. The patient has received an investigational drug in the previous 30 days or is scheduled to receive any investigational drug during the study period.
8. The patient has taken/received any medication of moderate or high emetogenic potential within the 48 hours prior to the first dose of study medications. Opiate drugs for cancer pain will be permitted if the patient has been on a stable dose and has not experienced emesis or clinically significant nausea from the narcotics in the 24 hours preceding the first dose of study medication.
9. The patient has taken/received any medication with known or potential antiemetic activity within the 24-hour period prior to receiving study drugs. This includes, but is not limited to:
* 5-HT3 receptor antagonists (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron). Palonosetron is not permitted within 7 days prior to receiving study drugs.
* Benzamide / benzamide derivatives (e.g., metoclopramide, alizapride).
* Benzodiazepines (except if the patient is receiving such medication for sleep or anxiety and has been on a stable dose for at least seven days prior to the first dose of study medications).
* Phenothiazines (e.g., prochlorperazine, promethazine, metopimazine, fluphenazine, perphenazine, thiethylperazine, chlorpromazine).
* Butyrophenone (e.g., haloperidol, droperidol).
* Corticosteroids (e.g., dexamethasone, methylprednisolone, prednisolone; with the exception of topical steroids for skin disorders, inhaled steroids for respiratory disorders).
* Anticholinergics (e.g., scopolamine).
* Antihistamines (e.g., cyclizine, hydroxyzine, diphenhydramine).
* Domperidone.
* Cannabinoids.
* Mirtazapine.
* Olanzapine.
10. The patient has taken/received strong or moderate inhibitors of CYP3A4 within seven (7) days prior to administration of study drugs (see Section 10.3.1., "Inhibitors of CYP3A4").
11. The patient has taken/received inducers of CYP3A4 within thirty (30) days prior to the administration of study drugs (see Section 10.3.2., "Inducers of CYP3A4").
18 Years
FEMALE
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Helsinn Healthcare SA
INDUSTRY
Christina Ruhlmann
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Christina Ruhlmann
Principal investigator
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Christina H. Ruhlmann, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Odense University Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Department of Oncology, Odense University Hospital
Odense, , Denmark
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Christina H. Ruhlmann, MD, PhD
Role: primary
Annemieke Sibtsen, RN
Role: backup
References
Explore related publications, articles, or registry entries linked to this study.
Detlefsen SS, Andersen DS, Knudsen AO, Nottrup TJ, Moller S, Nyvang GB, Jorgensen TL, Herrstedt J, Ruhlmann CH. Safety and antiemetic efficacy of weekly administration of netupitant/palonosetron plus dexamethasone during 5 weeks of concomitant chemo-radiotherapy-the DANGER-emesis study. Support Care Cancer. 2025 May 28;33(6):509. doi: 10.1007/s00520-025-09573-9.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
DANGER-emesis
Identifier Type: -
Identifier Source: org_study_id