Aprepitant and Granisetron for the Prophylaxis of Radiation Induced Nausea and Vomiting - A Pilot Study

• Sponsor: Sunnybrook Health Sciences Centre (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01183481
• Collaborator: Merck Frosst Canada Ltd. (Industry)
• Enrollment: 19
• Location: 1
• Arm: 1
• Duration (Months): 26
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The primary objective of this pilot study is to examine the efficacy of Aprepitant given in combination with Granisetron for the prevention of delayed-phase RINV in 84 patients receiving a single 8Gy of moderately emetogenic palliative RT in the RRRP at Sunnybrook Odette Cancer Centre for painful bony metastases from any primary solid tumor. Patients will be given a single dose of Granisetron 2 mg orally and Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the radiation treatment.. Secondary objectives include determining the complete RINV prophylaxis rate (acute and delayed phases), the partial emesis control rate, the safety of the combined regime, QOL issues, the time to the first emetic event and the time to the first use of rescue medication .

Condition or Disease	Intervention/Treatment	Phase
Nausea; Vomiting	Drug: Aprepitant; Radiation: Palliative radiation therapy; Drug: Granisetron	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Aprepitant and Granisetron for the Prophylaxis of Radiation Induced Nausea and Vomiting - A Pilot Study
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Aprepitant and Granisetron Patients will be given a single dose of Granisetron 2 mg orally and Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the Palliative radiation therapy.

Drug: Aprepitant; Patients will be given a single dose of Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the radiation treatment.; Radiation: Palliative radiation therapy; Moderately emetogenic palliative radiation therapy (RT) will be administered to all patients on the study.; Drug: Granisetron; Patients will be given a single dose of both Granisetron 2 mg orally on Day 0 (at least one hour before on the day of RT).

Outcome Measures

Primary Outcome Measures

1. The Proportion of Patients Experiencing no Vomiting and no Nausea, Without Use of Any Rescue Antiemetic Medication(s), From Days 2-10 Following the Radiation Therapy (Delayed RINV). [Days 2-10 following radiotherapy]

   Assessments of nausea, vomiting, and antiemetic use will be taken daily within 2-10 following the radiation therapy based on patient self-report nausea/vomiting diaries.

Secondary Outcome Measures

1. The Complete RINV Prophylaxis Rate (Acute and Delayed Phases), the Partial Emesis Control Rate, the Safety of the Combined Regime, QOL Issues, the Time to the First Emetic Event and Use of Rescue Medication . [From day of radiotherapy to 10 days following radiotherapy]

   Data will be measured by research staff at baseline and patient self-report nausea diaries will be taken on each day within this time frame.

2. Control Rate of Acute Phase Nausea, Vomiting, and Retching in Patients Undergoing Single Fraction Radiotherapy [Day of radiotherapy and 24 hours following]

   Percentage of participants experiencing no nausea, vomiting, and retching during the acute phase was assessed. Assessments of nausea, vomiting, and antiemetic use will be taken daily following the radiation therapy based on patient self-report nausea/vomiting diaries.

3. Control Rate of Delayed Phase Nausea, Vomiting, and Retching in Patients Undergoing Single Fraction Radiotherapy [Days 2-10 following radiotherapy]

   Percentage of participants in the single fraction arm experiencing no nausea, vomiting, and retching was assessed. Assessments of nausea, vomiting, and antiemetic use will be taken daily within 2-10 following the radiation therapy based on patient self-report nausea/vomiting diaries.

4. Control Rate of Acute Phase Nausea, Vomiting, and Retching in Patients Undergoing Multiple Fraction Radiotherapy [During radiotherapy (5 days) and the 24 hours following radiotherapy]

   Percentage of participants in the multiple fraction arm experiencing no nausea, vomiting, and retching was assessed. Data will be measured by research staff at baseline and patient self-report nausea diaries will be taken on each day within this time frame.

5. Control Rate of Delayed Phase Nausea, Vomiting, and Retching in Patients Undergoing Multiple Fraction Radiotherapy [Days 2-10 following radiotherapy]

   Percentage of participants experiencing no nausea, vomiting, and retching was assessed. Assessments of nausea, vomiting, and antiemetic use will be taken daily within 2-10 following the radiation therapy based on patient self-report nausea/vomiting diaries.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with bone metastases from any primary solid tumor site scheduled to receive a single 8 Gy fraction of palliative radiotherapy considered to be moderately emetogenic (an area of at least 80 cm2 in the anterior/posterior direction and located between the level of upper border of T11 and the lower border of L3) in the RRRP at Sunnybrook Odette Cancer Centre will be considered eligible.

Exclusion Criteria:

• Exclusion criteria include having nausea or vomiting 24hrs prior to radiation

• Having received or being scheduled to receive cranial radiation, moderately or highly emetogenic cytotoxic therapy 7 days prior to, during, or after radiation, receiving corticosteroids (except inhaled or topical), 5HT3 receptor antagonists or NK-1 antagonists or other antiemetic medication, being allergic to study medications, having a KPS<40, being pregnant or of childbearing potential and not using contraceptive measures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Odette Cancer Centre, Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N3M5

Sponsors and Collaborators

• Sunnybrook Health Sciences Centre
• Merck Frosst Canada Ltd.

Investigators

• Principal Investigator: Edward Chow, MBBS PhD FRCPC, Odette Cancer Centre, Sunnybrook Health Sciences Centre

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Dr. Edward Chow, Professor, Sunnybrook Health Sciences Centre
• ClinicalTrials.gov Identifier: NCT01183481
• Other Study ID Numbers: RINV Prophylaxis
• First Posted: Aug 17, 2010
• Last Update Posted: Oct 9, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by Dr. Edward Chow, Professor, Sunnybrook Health Sciences Centre: nausea; vomiting; antiemetics; radiotherapy; Radiation-induced nausea and vomiting
• Additional relevant MeSH terms: Nausea; Vomiting; Aprepitant; Granisetron

Study Results

Participant Flow

Recruitment Details	Patients were enrolled between January 2011 and October 2012 in a radiation oncology clinic
Pre-assignment Detail	No enrolled patients were later excluded.

Arm/Group Title	Aprepitant and Granisetron
Arm/Group Description	Patients will be given a single dose of Granisetron 2 mg orally and Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the radiation treatment.
Period Title: Overall Study
STARTED	19
COMPLETED	19
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Aprepitant and Granisetron
Arm/Group Description	Patients will be given a single dose of Granisetron 2 mg orally and Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the radiation treatment.
Overall Participants	19
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 31.6%
>=65 years	13 68.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.4 (15.48)
Sex: Female, Male (Count of Participants)
Female	11 57.9%
Male	8 42.1%
Region of Enrollment (participants) [Number]
Canada	19 100%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Patients Experiencing no Vomiting and no Nausea, Without Use of Any Rescue Antiemetic Medication(s), From Days 2-10 Following the Radiation Therapy (Delayed RINV).
Description	Assessments of nausea, vomiting, and antiemetic use will be taken daily within 2-10 following the radiation therapy based on patient self-report nausea/vomiting diaries.
Time Frame	Days 2-10 following radiotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aprepitant and Granisetron
Arm/Group Description	Patients will be given a single dose of Granisetron 2 mg orally and Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the radiation treatment.
Measure Participants	19
Number [participants]	19 100%

2. Secondary Outcome

Title	The Complete RINV Prophylaxis Rate (Acute and Delayed Phases), the Partial Emesis Control Rate, the Safety of the Combined Regime, QOL Issues, the Time to the First Emetic Event and Use of Rescue Medication .
Description	Data will be measured by research staff at baseline and patient self-report nausea diaries will be taken on each day within this time frame.
Time Frame	From day of radiotherapy to 10 days following radiotherapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Control Rate of Acute Phase Nausea, Vomiting, and Retching in Patients Undergoing Single Fraction Radiotherapy
Description	Percentage of participants experiencing no nausea, vomiting, and retching during the acute phase was assessed. Assessments of nausea, vomiting, and antiemetic use will be taken daily following the radiation therapy based on patient self-report nausea/vomiting diaries.
Time Frame	Day of radiotherapy and 24 hours following

Outcome Measure Data

Analysis Population Description

Patients undergoing single fraction treatment

Arm/Group Title	Aprepitant and Granisetron
Arm/Group Description	Patients will be given a single dose of Granisetron 2 mg orally and Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the Palliative radiation therapy. Aprepitant: Patients will be given a single dose of Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the radiation treatment. Palliative radiation therapy: Moderately emetogenic palliative radiation therapy (RT) will be administered to all patients on the study. Granisetron: Patients will be given a single dose of both Granisetron 2 mg orally on Day 0 (at least one hour before on the day of RT).
Measure Participants	13
Control rate of acute phase nausea	100 526.3%
Control rate of acute phase vomiting/retching	100 526.3%

4. Secondary Outcome

Title	Control Rate of Delayed Phase Nausea, Vomiting, and Retching in Patients Undergoing Single Fraction Radiotherapy
Description	Percentage of participants in the single fraction arm experiencing no nausea, vomiting, and retching was assessed. Assessments of nausea, vomiting, and antiemetic use will be taken daily within 2-10 following the radiation therapy based on patient self-report nausea/vomiting diaries.
Time Frame	Days 2-10 following radiotherapy

Outcome Measure Data

Analysis Population Description

Patients undergoing single fraction treatment

Arm/Group Title	Aprepitant and Granisetron
Arm/Group Description	Patients will be given a single dose of Granisetron 2 mg orally and Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the Palliative radiation therapy. Aprepitant: Patients will be given a single dose of Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the radiation treatment. Palliative radiation therapy: Moderately emetogenic palliative radiation therapy (RT) will be administered to all patients on the study. Granisetron: Patients will be given a single dose of both Granisetron 2 mg orally on Day 0 (at least one hour before on the day of RT).
Measure Participants	13
Control rate of delayed phase nausea	62 326.3%
Control rate of delayed phase vomiting/retching	85 447.4%

5. Secondary Outcome

Title	Control Rate of Acute Phase Nausea, Vomiting, and Retching in Patients Undergoing Multiple Fraction Radiotherapy
Description	Percentage of participants in the multiple fraction arm experiencing no nausea, vomiting, and retching was assessed. Data will be measured by research staff at baseline and patient self-report nausea diaries will be taken on each day within this time frame.
Time Frame	During radiotherapy (5 days) and the 24 hours following radiotherapy

Outcome Measure Data

Analysis Population Description

Patients undergoing multiple fraction treatment

Arm/Group Title	Aprepitant and Granisetron
Arm/Group Description	Patients will be given a single dose of Granisetron 2 mg orally and Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the Palliative radiation therapy. Aprepitant: Patients will be given a single dose of Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the radiation treatment. Palliative radiation therapy: Moderately emetogenic palliative radiation therapy (RT) will be administered to all patients on the study. Granisetron: Patients will be given a single dose of both Granisetron 2 mg orally on Day 0 (at least one hour before on the day of RT).
Measure Participants	6
Control rate of acute phase nausea	67 352.6%
Control rate of acute phase vomiting/retching	67 352.6%

6. Secondary Outcome

Title	Control Rate of Delayed Phase Nausea, Vomiting, and Retching in Patients Undergoing Multiple Fraction Radiotherapy
Description	Percentage of participants experiencing no nausea, vomiting, and retching was assessed. Assessments of nausea, vomiting, and antiemetic use will be taken daily within 2-10 following the radiation therapy based on patient self-report nausea/vomiting diaries.
Time Frame	Days 2-10 following radiotherapy

Outcome Measure Data

Analysis Population Description

Patients undergoing multiple fraction treatment

Arm/Group Title	Aprepitant and Granisetron
Arm/Group Description	Patients will be given a single dose of Granisetron 2 mg orally and Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the Palliative radiation therapy. Aprepitant: Patients will be given a single dose of Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the radiation treatment. Palliative radiation therapy: Moderately emetogenic palliative radiation therapy (RT) will be administered to all patients on the study. Granisetron: Patients will be given a single dose of both Granisetron 2 mg orally on Day 0 (at least one hour before on the day of RT).
Measure Participants	6
Control rate of delayed phase nausea	83 436.8%
Control rate of delayed phase vomiting/retching	83 436.8%

Adverse Events

Arm/Group Title	Aprepitant and Granisetron
Arm/Group Description	Patients will be given a single dose of Granisetron 2 mg orally and Aprepitant 125 mg on Day 0 (at least one hour before on the day of RT) followed by 80 mg of Aprepitant once daily in the mornings on Days 1 and 2 following the radiation treatment.
All Cause Mortality
	Aprepitant and Granisetron
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Aprepitant and Granisetron
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Other (Not Including Serious) Adverse Events
	Aprepitant and Granisetron
	Affected / at Risk (%)	# Events
Total	1/19 (5.3%)
Musculoskeletal and connective tissue disorders
Pain crisis	1/19 (5.3%)

Limitations/Caveats

Small number of subjects results in early termination of study

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.