Unknown status
`Verified2021-12 by Christina Ruhlmann, Odense University Hospital
`Last known status was: Recruiting
`Safety and Antiemetic Efficacy of Akynzeo Plus Dexamethasone During
`Radiotherapy and Concomitant Weekly Cisplatin
`ClinicalTrials.gov ID NCT03668639
`SponsorChristina Ruhlmann
`Information provided byChristina Ruhlmann, Odense University Hospital (Responsible Party)
`Last Update Posted 2021-12-14
`Study Details Tab
`Study Overview
`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.
`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.
`The U.S. government does not review or approve the safety and science of all studies
`listed on this website.
`Read our full disclaimer(https://clinicaltrials.gov/about-site/disclaimer) for details.
`Detailed Description
`8/3/25, 4:05 PM Study Details | Safety and Antiemetic Efficacy of Akynzeo Plus Dexamethasone During Radiotherapy and Concomitant Weekly Cispl…
`https://clinicaltrials.gov/study/NCT03668639 1/12
`HELSINN EXHIBIT 2025
`Azurity Pharmaceuticals, Inc. v. Helsinn Healthcare S.A.
`IPR2025-00948
`Page 1 of 12
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`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.
`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
`Conditions
`Chemotherapy-induced Nausea and VomitingAdverse EventCervical Cancer
`Intervention / Treatment
`Drug: Akynzeo
`Drug: Dexamethasone
`Other Study ID Numbers
`Study Start (Actual)
`2018-09-05
`Primar
`y Completion (Estimated)
`2023-03-01
`Study Completion (Estimated)
`2023-04-15
`Enrollment (Estimated)
`80
`Study Typ
`e
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`Interventional
`Phase
`Phase 2
`Phase 3
`Resource links provided by the National Library of Medicine
`MedlinePlus(https://medlineplus.gov/) related topics:  Nausea and
`Vomiting(https://medlineplus.gov/nauseaandvomiting.html)
`Drug Information(https://dailymed.nlm.nih.gov/dailymed/) available for: 
`Dexamethasone(https://dailymed.nlm.nih.gov/dailymed/search.cfm?
`labeltype=human&query=Dexamethasone)Dexamethasone sodium
`phosphate(https://dailymed.nlm.nih.gov/dailymed/search.cfm?
`labeltype=human&query=Dexamethasone+sodium+phosphate)Dexamethasone
`acetate(https://dailymed.nlm.nih.gov/dailymed/search.cfm?
`labeltype=human&query=Dexamethasone+acetate)
`FDA Drug and Device Resources(https://clinicaltrials.gov/fda-links)
`Contacts and Locations
`This section provides contact details for people who can answer questions about joining this study, and
`information on where this study is taking place.
`To learn more, please see the Contacts and Locations section in How to Read a Study
`Record(https://clinicaltrials.gov/study-basics/how-to-read-study-record#contacts-and-locations).
`This study has 1 location
`Denmark
`Study Contact
`Name: Christina H. Ruhlmann, MD, PhD
`Phone Number: 22314446 ext +45
`Email: christina.ruhlmann@rsyd.dk
`Study Contact Backup
`Name: Annemieke Sibtsen Sibtsen, RN
`Phone Number: 40467103 ext +45
`Email: Annemieke.Sibtsen@rsyd.dk
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`Odense, Denmark, 5000
`Recruiting
`Department of Oncology, Odense University
`Hospital
`Contact :Christina H. Ruhlmann, MD, PhD
`22314446 ext +45
`christina.ruhlmann@rsyd.dk
`Contact :Annemieke Sibtsen, RN
`29427758 ext +45
`Annemieke.Sibtsen@rsyd.dk
`Principal Investigator :Christina H. Ruhlmann,
`MD, PhD
`Sub-Investigator :Anja Ør Knudsen, MD
`Participation Criteria
`Researchers look for people who fit a certain description, called
`eligibility criteria. Some examples of
`these criteria are a person's general health condition or prior treatments.
`For general information about clinical research, read Learn About
`Studies(https://clinicaltrials.gov/study-basics/learn-about-studies).
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`Eligibility Criteria
`Description
`Inclusion Criteria:
`1. The patient has a diagnosis of cervical cancer.
`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.
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`Exclusion Criteria:
`1. The patient has a current malignant diagnosis other than cervical cancer, with exception of
`non-melanoma skin cancers.
`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.
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`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").
`Gender-based Eligibility
`Yes
`Gender Eligibility for Study
`Patients with cervical cancer.
`Ages Eligible for Study
`18 Years and older (Adult,  Older Adult)
`Sexes Eligible for Study
`Female
`Accepts Healthy Volunteers
`No
`Study Plan
`This section provides details of the study plan, including how the study is designed and what the study
`is measuring.
`How is the study designed?
`Design Details
`Primary Purpose : Supportive Care
`Allocation : N/A
`Interventional Model : Single Group Assignment
`Masking : None (Open Label)
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`What is the study measuring?
`Primary Outcome Measures
`Arms and Interventions
`Participant Group/ArmIntervention/Treatment
`Other: 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.
`Drug: Akynzeo
`Weekly administration of akynzeo for five
`weeks.
`Drug: Dexamethasone
`Weekly administration of dexamethasone 12
`mg Day 1, 8 mg Day 2-3, and 4 mg Day 4 for
`five weeks.
`Outcome
`Measure Measure Description Time
`Frame
`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
`Measurement of incidence of nausea and
`vomiting and use of rescue antiemetics.
`Five
`weeks.
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`Secondary Outcome Measures
`measured by
`incidence of
`nausea and
`vomiting and
`use of rescue
`antiemetics
`Outcome
`Measure Measure Description Time
`Frame
`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.
`Five
`days
`and five
`weeks.
`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.
`Five
`days
`and five
`weeks.
`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.
`Five
`days
`and five
`weeks.
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`Collaborators and Investigators
`This is where you will find people and organizations involved with this study.
`Christina Ruhlmann
`Study Record Dates
`These dates track the progress of study record and summary results submissions to ClinicalTrials.gov.
`Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure
`they meet specific quality control standards before being posted on the public website.
`Study Registration Dates
`First Submitted
`2018-01-28
`First Submitted that Met QC Criteria
`2018-09-10
`First Posted
`2018-09-12
`Study Record Updates
`Last Update Submitted that met QC Criteria
`2021-12-12
`Time to first
`emetic episode
`To investigate Akynzeo and dexamethasone in
`terms of time to first emetic episode.
`Five
`weeks.
`Sponsor
`Collaborators
`Helsinn Healthcare SA
`Investigators
`Principal Investigator:Christina H. Ruhlmann, MD, PhD, Odense University Hospital
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`Last Update Posted
`2021-12-14
`Last Verified
`2021-12
`More Information
`Terms related to this study
`Plan for Individual Participant Data (IPD)
`Drug and device information, study documents, and helpful links
`HHS Vulnerability Disclosure
`Additional Relevant MeSH Terms
`Signs and Symptoms, Digestive
`Vomiting
`Anti-Inflammatory Agents
`Antiemetics
`Autonomic Agents
`Peripheral Nervous System Agents
`Physiological Effects of Drugs
`Gastrointestinal Agents
`Glucocorticoids
`Hormones
`Hormones, Hormone Substitutes, and Hormone Antagonists
`Antineoplastic Agents, Hormonal
`Antineoplastic Agents
`Dexamethasone
`Plan to Share Individual Participant Data (IPD)?
`No
`Studies a U.S. FDA-Regulated Drug Product
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`No
`Studies a U.S. FDA-Regulated Device Product
`No
`Product Manufactured in and Exported from the U.S.
`No
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