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Chemotherapy-induced Nausea and VomitingPhase 2/3NCT03668639

Safety and Antiemetic Efficacy of Akynzeo Plus Dexamethasone During Radiotherapy and Concomitant Weekly Cisplatin

A Phase 2/3 study testing Akynzeo and Dexamethasone in people with Chemotherapy-induced Nausea and Vomiting and Adverse Event, run by Christina Ruhlmann at 1 site in Denmark.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is a multicentre, single-arm, phase II study to investigate the safety and antiemetic efficacy of Akynzeo (a fixed dose combination of palonosetron and netupitant) plus dexamethasone in patients receiving concomitant chemo-radiotherapy with weekly cisplatin for at least five weeks. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Akynzeo and Dexamethasone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteDenmark
Study dates
5 Sep 2018to 15 Apr 2023
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The patient has a diagnosis of cervical cancer.
  • The patient understands the nature and purpose of this study and the study procedures and has signed informed consent.
  • The patient is aged ≥ 18 years.
  • 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.
  • The patient is scheduled to receive fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2 for at least five weeks.
  • Brachy therapy is scheduled to be initiated after the third cycle of weekly cisplatin, and preferentially after the fifth week of treatment.
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  • Chemotherapy with an emetic risk potential of minimal or mild (up to 30%) is allowed on days 1-4 (see ref. 14).
  • The patient has a WHO Performance Status of ≤ 2.
  • 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
  • The patient is able to read, understand, and complete questionnaires and daily components of the Patient Diary for each study cycle.
  • 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.

Who cannot join

  • The patient has a current malignant diagnosis other than cervical cancer, with exception of non-melanoma skin cancers.
  • The patient is pregnant or lactating.
  • 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.
  • 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.
  • The patient has a known hypersensitivity or contraindication to palonosetron, another 5-HT3 receptor antagonist, dexamethasone, or netupitant.
  • The patient has previously received an NK1 receptor antagonist.
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  • The patient has received an investigational drug in the previous 30 days or is scheduled to receive any investigational drug during the study period.
  • 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.
  • 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.
  • 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").
  • 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").

Trial locations and contacts

1 site in 1 country.

Christina H. Ruhlmann, MD, PhD contact

22314446 ext. +45

christina.ruhlmann@rsyd.dk

Annemieke Sibtsen Sibtsen, RN contact

40467103 ext. +45

Annemieke.Sibtsen@rsyd.dk

Denmark1 site, 1 recruiting

  • Department of Oncology, Odense University Hospital

    Odense, 5000

    Christina H. Ruhlmann, MD, PhD, 22314446 ext. +45, christina.ruhlmann@rsyd.dk

    Annemieke Sibtsen, RN, 29427758 ext. +45, Annemieke.Sibtsen@rsyd.dk

    Recruiting

Other trials in Denmark

About this study

Official title: A Study to Investigate the Safety and Antiemetic Efficacy of Akynzeo Plus Dexamethasone in Patients Receiving Concomitant Chemo-radiotherapy With Weekly Cisplatin for at Least Five Weeks

This is a multicentre, single-arm, phase II study to investigate the safety and antiemetic efficacy of Akynzeo (a fixed dose combination of palonosetron and netupitant) plus dexamethasone in patients receiving concomitant chemo-radiotherapy with weekly cisplatin for at least five weeks.

Read the detailed description

Akynzeo contains a combination of the neurokinin-1 receptor antagonist netupitant and the serotonin receptor antagonist palonosetron. Akynzeo is approved as antiemetic prophylaxis in patients receiving high emetogenic chemotherapy e.g. high dose cisplatin administered every three weeks.

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.

Being tested
Akynzeo, Dexamethasone
Medical subject headings
Vomiting, Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AkynzeoDrug

    Weekly administration of akynzeo for five weeks.

  • DexamethasoneDrug

    Weekly administration of dexamethasone 12 mg Day 1, 8 mg Day 2-3, and 4 mg Day 4 for five weeks.

Study groups in NCT03668639
Study groupRoleWhat they receive
Akynzeo plus dexamethasoneOtherAkynzeo (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.
Receives: Drug: Akynzeo; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of weekly administration of Akynzeo measured by incidence of treatment-emergent adverse events

    Measurement of incidence of treatment-emergent adverse events.

    Measured: Five weeks.

  2. Efficacy of weekly administration of Akynzeo measured by incidence of nausea and vomiting and use of rescue antiemetics

    Measurement of incidence of nausea and vomiting and use of rescue antiemetics.

    Measured: Five weeks.

Secondary outcomes (4)

  1. Complete response in terms of the proportion of subjects with complete response

    To investigate Akynzeo and dexamethasone in terms of the proportion of subjects with complete response (defined as no vomits, no dry retches and no need for rescue medication) in the 5 days and the 35 days following initiation of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.

    Measured: Five days and five weeks.

  2. No significant nausea in terms of the proportion of subjects with no significant nausea

    To investigate Akynzeo and dexamethasone in terms of the proportion of subjects with no significant nausea (none or mild nausea) in the 5 days and the 35 days following initiation of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.

    Measured: Five days and five weeks.

  3. No nausea in terms of the proportion of subjects with no nausea

    To investigate Akynzeo and dexamethasone in terms of the proportion of subjects with no nausea in the 5 days and the 35 days following initiation of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.

    Measured: Five days and five weeks.

  4. Time to first emetic episode

    To investigate Akynzeo and dexamethasone in terms of time to first emetic episode.

    Measured: Five weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Sep 2018
  2. Study start5 Sep 2018
  3. Primary completion1 Mar 2023 (estimated)
  4. Study completion15 Apr 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Supportive care
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03668639
Sponsor's protocol ID
DANGER-emesis
Status last verified
Dec 2021
First submitted
28 Jan 2018
Last updated
14 Dec 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40437122

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Akynzeo and Dexamethasone in people with Chemotherapy-induced Nausea and Vomiting and Adverse Event, run by Christina Ruhlmann at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 14 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Christina H. Ruhlmann, MD, PhD (22314446 ext. +45, christina.ruhlmann@rsyd.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of weekly administration of Akynzeo measured by incidence of treatment-emergent adverse events (time frame: Five weeks.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03668639, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2021.

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