Efficacy of Two Antiemetic Regimens in Patients Receiving Radiotherapy and Concomitant Weekly Cisplatin

NCT01074697 | Completed Phase 3 DMC

• 2 other identifiers: GAND-emesis2009-014691-21
• Study Type: interventional
• Target: 246
• Locations: 4 countries
• Sites: 8

Brief Summary

GAND-emesis is a multinational, randomized, double-blind, placebo-controlled, parallel-group study to investigate the efficacy and tolerability of a neurokinin1 receptor antagonist (fosaprepitant dimeglumine) in combination with an antiemetic (anti-nausea-and-vomiting) control regimen (palonosetron and dexamethasone) in patients with a gynaecological cancer diagnosis, who are scheduled to receive radiotherapy and weekly chemotherapy. The study aims at investigating if a three-drug antiemetic regimen is superior to a two-drug regimen (standard treatment) in preventing nausea and vomiting in patients receiving radiotherapy and weekly chemotherapy. A pilot study demonstrated that approximately 50% of patients will experience nausea and vomiting when offered a two-drug antiemetic regimen, and it is expected that addition of a third drug (a neurokinin1 receptor antagonist) can increase the proportion of patients with no vomiting in the course of combined chemo-radiotherapy.

Conditions

Nausea; Vomiting; Genital Neoplasms, Female

Keywords

Randomized Controlled Trial; Serotonin Agonists; Dexamethasone; Receptors, Neurokinin-1; Radiotherapy; Cisplatin; Prevention & control

Outcome Measures

Primary Outcomes (1)

• To compare fosaprepitant dimeglumine, palonosetron, and dexamethasone with palonosetron, dexamethasone, and placebo with respect to efficacy; the proportion of subjects with no vomiting during five weeks of radiotherapy and concomitant weekly cisplatin.

  35 days

Secondary Outcomes (7)

• To compare the fosaprepitant dimeglumine regimen and the control regimen in terms of the proportion of subjects with complete response in the 7 days following initiation of radiotherapy and concomitant weekly cisplatin.

  7 days

• To compare the fosaprepitant dimeglumine regimen and the control regimen in terms of the proportion of subjects with no significant nausea during five weeks of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.

  35 days

• To compare the fosaprepitant dimeglumine regimen and the control regimen with respect to complete response in the 35 days following initiation of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.

  35 days

• To compare the fosaprepitant dimeglumine regimen and the control regimen in terms of the proportion of subjects with no nausea during five weeks (35 days) of fractionated radiotherapy and concomitant weekly cisplatin at a dose of ≥ 40 mg/m2.

  35 days

• To compare the fosaprepitant dimeglumine regimen and the control regimen in terms of the number of days to first emetic episode.

  0-35 days

Study Arms (2)

Fosaprepitant dimeglumine

ACTIVE COMPARATOR

Drug: Fosaprepitant dimeglumine

Saline water

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Fosaprepitant dimeglumine DRUG

Addition of fosaprepitant dimeglumine 150 mg IV single dose weekly (before chemotherapy) to dexamethasone and palonosetron.

Also known as: Palonosetron, Dexamethasone

Fosaprepitant dimeglumine

Placebo DRUG

Saline water

Saline water

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has a diagnosis 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.

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 aged \< 18 years.
• The patient is scheduled to receive less than five weeks of fractionated radiotherapy and concomitant weekly cisplatin.
• Brachy therapy is planned to be initiated before the third cycle of weekly cisplatin.
• The patient has been previously treated with radiotherapy, and/or chemotherapy, with exception of treatment with low voltage RT or electron RT for non-melanoma skin cancers .
• The patient has a WHO Performance Status of \> 2.

Sponsors & Collaborators

• Odense University Hospital: lead
• Helsinn Healthcare SA: collaborator

Study Sites (8)

RAH Cancer Centre, Royal Adelaide Hospital

Adelaide SA, 5000, Australia

Location

Department of Oncology

Aarhus, 8000, Denmark

Location

Rigshospitalet, Finsen Centret

Copenhagen, 2100, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Department of Oncology, Odense University Hospital

Odense, 5000, Denmark

Location

Vivantes Klinikum Neukolln

Berlin, Germany

Location

Universitatsklinikum Schleswig Holstein

Kiel, 24105, Germany

Location

The Norwegian Radium Hospital

Oslo, 0310, Norway

Location

Related Publications (1)

• Ruhlmann CH, Christensen TB, Dohn LH, Paludan M, Ronnengart E, Halekoh U, Hilpert F, Feyer P, Kristensen G, Hansen O, Keefe D, Herrstedt J. Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol. 2016 Apr;17(4):509-518. doi: 10.1016/S1470-2045(15)00615-4. Epub 2016 Mar 4.

  PMID: 26952945 DERIVED

MeSH Terms

Conditions

Nausea; Vomiting; Genital Neoplasms, Female

Interventions

fosaprepitant; Palonosetron; Dexamethasone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Jorn Herrstedt, MD, DMSci

  Odense University Hospital

  STUDY DIRECTOR

• Christina Ruhlmann, MD

  Odense University Hospial

  PRINCIPAL INVESTIGATOR

• Dorothy Keefe, MD, FRACP

  Royal Adelaide Hospital

  PRINCIPAL INVESTIGATOR

• Petra Feyer, MD, DMSci

  Vivantes Klinikum Neukölln in Berlin

  PRINCIPAL INVESTIGATOR

• Thomas Broe Christensen, MD, PhD

  Herlev Hospital

  PRINCIPAL INVESTIGATOR

• Gunnar Kristensen, MD, PhD

  Norwegian Radium Hospital

  PRINCIPAL INVESTIGATOR

• Henrik Roed, MD, DMSci

  The Finsen Centre, Copenhagen University Hospital

  PRINCIPAL INVESTIGATOR

• Felix Hilpert, MD, DMSci

  University Hospital Schleswig-Holstein

  PRINCIPAL INVESTIGATOR

• Jacob C Lindegaard, MD

  Department of Oncology,Aarhus University Hospital, Aarhus, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 23, 2010
• First Posted: February 24, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: April 24, 2015

Record last verified: 2015-04

Locations

NO (1); DE (2); DK (4); AU (1)