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

NCT03668639 | Unknown Phase 2 DMC

• 1 other identifier: DANGER-emesis
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chemotherapy-induced Nausea and Vomiting; Adverse Event; Cervical Cancer

Outcome Measures

Primary Outcomes (2)

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

  Measurement of incidence of treatment-emergent adverse events.

  Five weeks.

• 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.

  Five weeks.

Secondary Outcomes (4)

• Complete response in terms of the proportion of subjects with complete response

  Five days and five weeks.

• No significant nausea in terms of the proportion of subjects with no significant nausea

  Five days and five weeks.

• No nausea in terms of the proportion of subjects with no nausea

  Five days and five weeks.

• Time to first emetic episode

  Five weeks.

Study Arms (1)

Akynzeo plus dexamethasone

OTHER

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.

Drug: Akynzeo; Drug: Dexamethasone

Interventions

Akynzeo DRUG

Weekly administration of akynzeo for five weeks.

Akynzeo plus dexamethasone

Dexamethasone DRUG

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

Akynzeo plus dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Patients with cervical cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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:
• 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).

Sponsors & Collaborators

• Christina Ruhlmann: lead
• Helsinn Healthcare SA: collaborator

Study Sites (1)

Department of Oncology, Odense University Hospital

Odense, 5000, Denmark

RECRUITING

Related Publications (1)

• 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.

  PMID: 40437122 DERIVED

MeSH Terms

Conditions

Vomiting; Uterine Cervical Neoplasms

Interventions

netupitant, palosentron drug combination; Dexamethasone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Christina H. Ruhlmann, MD, PhD

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christina H. Ruhlmann, MD, PhD

CONTACT

22314446; christina.ruhlmann@rsyd.dk

Annemieke Sibtsen Sibtsen, RN

CONTACT

40467103; Annemieke.Sibtsen@rsyd.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: January 28, 2018
• First Posted: September 12, 2018
• Study Start: September 5, 2018
• Primary Completion: March 1, 2023
• Study Completion: April 15, 2023
• Last Updated: December 14, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)