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

Primary Purpose

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

Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Akynzeo
Dexamethasone
Sponsored by
Christina Ruhlmann
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Chemotherapy-induced Nausea and Vomiting

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

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.
    • 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").

Sites / Locations

  • Department of Oncology, Odense University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Akynzeo plus dexamethasone

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
January 28, 2018
Last Updated
December 12, 2021
Sponsor
Christina Ruhlmann
Collaborators
Helsinn Healthcare SA
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1. Study Identification

Unique Protocol Identification Number
NCT03668639
Brief Title
Safety and Antiemetic Efficacy of Akynzeo Plus Dexamethasone During Radiotherapy and Concomitant Weekly Cisplatin
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
September 5, 2018 (Actual)
Primary Completion Date
March 1, 2023 (Anticipated)
Study Completion Date
April 15, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Christina Ruhlmann
Collaborators
Helsinn Healthcare SA

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy-induced Nausea and Vomiting, Adverse Event, Cervical Cancer

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Akynzeo plus dexamethasone
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Akynzeo
Intervention Description
Weekly administration of akynzeo for five weeks.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Weekly administration of dexamethasone 12 mg Day 1, 8 mg Day 2-3, and 4 mg Day 4 for five weeks.
Primary Outcome Measure Information:
Title
Safety of weekly administration of Akynzeo measured by incidence of treatment-emergent adverse events
Description
Measurement of incidence of treatment-emergent adverse events.
Time Frame
Five weeks.
Title
Efficacy of weekly administration of Akynzeo measured by incidence of nausea and vomiting and use of rescue antiemetics
Description
Measurement of incidence of nausea and vomiting and use of rescue antiemetics.
Time Frame
Five weeks.
Secondary Outcome Measure Information:
Title
Complete response in terms of the proportion of subjects with complete response
Description
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.
Time Frame
Five days and five weeks.
Title
No significant nausea in terms of the proportion of subjects with no significant nausea
Description
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.
Time Frame
Five days and five weeks.
Title
No nausea in terms of the proportion of subjects with no nausea
Description
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.
Time Frame
Five days and five weeks.
Title
Time to first emetic episode
Description
To investigate Akynzeo and dexamethasone in terms of time to first emetic episode.
Time Frame
Five weeks.

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Patients with cervical cancer.
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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: 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: 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").
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christina H. Ruhlmann, MD, PhD
Phone
22314446
Ext
+45
Email
christina.ruhlmann@rsyd.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Annemieke Sibtsen Sibtsen, RN
Phone
40467103
Ext
+45
Email
Annemieke.Sibtsen@rsyd.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christina H. Ruhlmann, MD, PhD
Organizational Affiliation
Odense University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Oncology, Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina H. Ruhlmann, MD, PhD
Phone
22314446
Ext
+45
Email
christina.ruhlmann@rsyd.dk
First Name & Middle Initial & Last Name & Degree
Annemieke Sibtsen, RN
Phone
29427758
Ext
+45
Email
Annemieke.Sibtsen@rsyd.dk
First Name & Middle Initial & Last Name & Degree
Christina H. Ruhlmann, MD, PhD
First Name & Middle Initial & Last Name & Degree
Anja Ør Knudsen, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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