Ondissolve in the Prophylaxis/Rescue of Radiation Induced Nausea and Vomiting

• Sponsor: Sunnybrook Health Sciences Centre (Other)
• Overall Status: Completed
• CT.gov ID: NCT02006056
• Collaborator: Takeda Canada, Inc. (Industry)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 7
• Patients Per Site Per Month: 4.3

Study Details

Study Description

Brief Summary

The primary objective of the study is to examine the efficacy of Ondissolve for the prevention/rescue of Acute and Delayed Phase radiation induced nausea and vomiting (RINV) in patients undergoing single or multiple fraction, emetogenic palliative radiation therapy for painful bone metastases. The study population will be 30 patients seen in the RRRP at the Sunnybrook Odette Cancer Centre receiving palliative radiation therapy considered emetogenic for bone metastases. Patients will take the study medication (Ondissolve 8 mg) twice on each day of radiation therapy, at least one hour prior to treatment and repeat approximately 6-8 hours later the same day. Patients undergoing multiple fraction radiation therapy will take Ondissolve on weekends or holidays in between treatment. Secondary objectives include to evaluate key secondary endpoints related to RINV, and to investigate the ease and length of administration of protocol medicine. We hypothesize that Ondissolve will be effective in the prophylaxis of RINV, and the ease of use and administration will provide an appropriate delivery method for those unable to tolerate the oral form of ondansetron.

Condition or Disease	Intervention/Treatment	Phase
Nausea; Vomiting	Drug: Ondansetron	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Prospective Study of Ondissolve in the Prophylaxis/Rescue of Radiation Induced Nausea and Vomiting - a Phase II Study
• Study Start Date: Nov 1, 2013
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Secondary prophylaxis Patients already experiencing mild nausea/vomiting within 24 hours before radiotherapy. Intervention is 8mg of ondansetron (Ondissolve) on the day of radiation treatment at least 1 hour prior to treatment and repeated approx. 608 hours later in the day (bid). For patients who are treated with 20Gy/5 fractions, or 30Gy/10 fractions, they will take ondansetron twice (bid) on each day of treatment, at least 1 hour prior to treatment, and also on weekends or holidays in between treatment.	Drug: Ondansetron; Patients will take Ondissolve (8mg) on the day of the radiation treatment at least one hour prior to treatment and repeat approximately 6-8 hours later in the day (bid). For patients who are being treated with 20Gy in 5 fractions, or 30 Gy in 10 fractions, this group will take Ondissolve twice (bid) on each day of treatment, at least 1 hour prior to treatment and also on weekends or holidays in between treatment.; Other Names: Ondissolve
Experimental: Primary prophylaxis Patients experiencing no nausea and vomiting 24 hours before commencement of radiotherapy. Intervention is 8mg of ondansetron (Ondissolve) on the day of radiation treatment at least 1 hour prior to treatment and repeated approx. 608 hours later in the day (bid). For patients who are treated with 20Gy/5 fractions, or 30Gy/10 fractions, they will take ondansetron twice (bid) on each day of treatment, at least 1 hour prior to treatment, and also on weekends or holidays in between treatment.	Drug: Ondansetron; Patients will take Ondissolve (8mg) on the day of the radiation treatment at least one hour prior to treatment and repeat approximately 6-8 hours later in the day (bid). For patients who are being treated with 20Gy in 5 fractions, or 30 Gy in 10 fractions, this group will take Ondissolve twice (bid) on each day of treatment, at least 1 hour prior to treatment and also on weekends or holidays in between treatment.; Other Names: Ondissolve

Outcome Measures

Primary Outcome Measures

1. Efficacy for the Prevention/Rescue of Radiation-induced Nausea and Vomiting. [Day 0 - Day 10]

   The primary objectives are to examine the efficacy for the prevention/rescue of Acute and Delayed Phase radiation-induced nausea and vomiting (RINV) in patients undergoing single or multiple fraction, emetogenic palliative radiation therapy for painful bone metastases. Complete control: No increase in emetic episodes or increase in use of rescue medication (for secondary prophylaxis) following radiation treatment, compared to the number of incidences at baseline. Partial control: Increase of 2 or fewer emetic episodes from baseline and no use of rescue antiemetic medication during or after radiotherapy. Uncontrolled: Increase of three or more emetic episodes or use of antiemetic rescue medication.

Other Outcome Measures

1. The European Organization for Research and Treatment of Cancer Quality of LIfe Questionnaire - C15 Palliative (C15-PAL), From Day 1-5 of Treatment. [Day 0-5 during treatment]

   Quality of life as measured by the EORTC QLQ-C15-PAL. For multiple fractions of radiotherapy, the questionnaire will be administered on Day 5 and 10 during treatment when applicable. Since the number of secondary prophylaxis patients was small (n=4), quality of life (QOL) analysis was done with two arms combined. Questions on the C15-PAL were scored on a scale of 0-100, with 0 representing no symptoms but low level of functioning and 100 representing severe symptoms and high degree of functioning.

2. The European Organization for Research and Treatment of Cancer Quality of LIfe Questionnaire - C15 Palliative (C15-PAL) on Day 6-10 of Treatment. [Day 6-10 of treatment]

   Quality of life as measured by the EORTC QLQ-C15-PAL. For multiple fractions of radiotherapy, the questionnaire will be administered on Day 5 and 10 during treatment when applicable. Since the number of secondary prophylaxis patients was small (n=4), quality of life (QOL) analysis was done with two arms combined. Questions on the C15-PAL were scored on a scale of 0-100, with 0 representing no symptoms but low level of functioning and 100 representing severe symptoms and high degree of functioning.

3. Functional Living Index-emesis (FLIE) at Day 3, Using Questions 2-9, 11-18 (Q1/Q10 Refer to Nausea/Vomiting and Therefore Are Part of Primary Objectives) [Day 3]

   Since the number of secondary prophylaxis patients was small (n=4), quality of life (QOL) analysis was done with two arms combined. Questions on the FLIE are reported from 1-7, with "1" being no symptoms and "not at all" for interference with life, and "7" being "a great deal" of symptom and interference with life. Q1-9 are for nausea (N). Q 10-18 are for vomiting (V). All questions refer to "during the past 3 days". Q1/10: How much N/V have you had? Q2/11: Has N/V affected your ability to maintain usual recreation or leisure activities? Q3/12: Has N/V affected your ability to make a meal or do minor household repairs? Q4/13: How much has N/V affected your ability to enjoy a meal? Q5/14: How much has N/V affected your ability to enjoy liquid refreshment? Q6/15: How much has N/V affected your willingness to see and spend time with family/friends? Q7/16: Has N/V affected your daily functioning? Q8/17: Degree your N/V imposed hardship on you? Q9/18: Degree on your family?

4. Functional Living Index-emesis (FLIE) at Day 7, Using Questions 2-9, 11-18 (Q1/Q10 Refer to Nausea/Vomiting and Therefore Are Part of Primary Objectives) [Day 7]

   Since the number of secondary prophylaxis patients was small (n=4), quality of life (QOL) analysis was done with two arms combined. Questions on the FLIE are reported from 1-7, with "1" being no symptoms and "not at all" for interference with life, and "7" being "a great deal" of symptom and interference with life. Q1-9 are for nausea (N). Q 10-18 are for vomiting (V). All questions refer to "during the past 3 days". Q1/10: How much N/V have you had? Q2/11: Has N/V affected your ability to maintain usual recreation or leisure activities? Q3/12: Has N/V affected your ability to make a meal or do minor household repairs? Q4/13: How much has N/V affected your ability to enjoy a meal? Q5/14: How much has N/V affected your ability to enjoy liquid refreshment? Q6/15: How much has N/V affected your willingness to see and spend time with family/friends? Q7/16: Has N/V affected your daily functioning? Q8/17: Degree your N/V imposed hardship on you? Q9/18: Degree on your family?

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed consent

• Patient will receive palliative radiation therapy considered emetogenic for bone metastases.

• Group 1: At least mild nausea and/or at least mild vomiting as recorded in the Baseline Nausea and Vomiting Data Collection Sheet

• Group 2: Nausea and vomiting recorded as 'none' in the Baseline Nausea and Vomiting Data Collection Sheet

Exclusion Criteria:

• Patient is scheduled to receive cranial radiation therapy during or within 10 days following completion of protocol RT.

• Patient received cranial RT within 7 days prior to commencement of protocol RT.

• Patient is scheduled to receive chemotherapy during or within 10 days following completion of protocol RT.

• Patient received moderately or highly emetogenic chemotherapy within 7 days prior to commencement of protocol RT.

• Patient is scheduled to change regimen/dose or start the use of corticosteroids (inhaled or topical permitted), or other medications considered to have antiemetic activity within 48 hours of protocol RT.

• Patient is scheduled to change regimen/dose or start the use of corticosteroids (inhaled or topical permitted), or other medications considered to have antiemetic activity during or within 10 days following completion of protocol RT.

• Patient is allergic to protocol medication.

• Patient has a Karnofsky Performance Status score <40.

• Patient is a woman who is pregnant or of childbearing potential and is 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	M4N 3M5

Sponsors and Collaborators

• Sunnybrook Health Sciences Centre
• Takeda Canada, Inc.

Investigators

• Principal Investigator: Edward Chow, MBBS PhD, 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: NCT02006056
• Other Study ID Numbers: Ondissolve
• First Posted: Dec 9, 2013
• Last Update Posted: Aug 16, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Nausea; Vomiting; Ondansetron

Study Results

Participant Flow

Recruitment Details	Patients attending the Odette Cancer Centre, Toronto, Canada, who satisfy the eligibility criteria were considered for entry into the trial. The last patient was enrolled July 2014.
Pre-assignment Detail	This prospective phase II trial enrolled patients from November 2013 to July 2014.

Arm/Group Title	Primary Prophylaxis	Secondary Prophylaxis
Arm/Group Description	Patients have no pre-existing nausea or vomiting 24 hours before radiotherapy	Patients already experiencing mild nausea and/or mild vomiting within 24 hours before radiotherapy.
Period Title: Overall Study
STARTED	26	4
COMPLETED	26	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Primary Prophylaxis	Secondary Prophylaxis	Total
Arm/Group Description	Patients had no nausea or vomiting at baseline.	Patients had nausea or vomiting at baseline.	Total of all reporting groups
Overall Participants	26	4	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.6 (11.7)	69.8 (5.7)	71.3 (11)
Sex: Female, Male (Count of Participants)
Female	10 38.5%	1 25%	11 36.7%
Male	16 61.5%	3 75%	19 63.3%
Location (Count of Participants)
Home	24 92.3%	4 100%	28 93.3%
Hospital	2 7.7%	0 0%	2 6.7%
Score on the KPS (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	69.2 (15.2)	70.0 (14.1)	69.3 (14.8)
Primary cancer site (Count of Participants)
Prostate	10 38.5%	1 25%	11 36.7%
Breast	8 30.8%	0 0%	8 26.7%
Lung	2 7.7%	1 25%	3 10%
Bladder	2 7.7%	0 0%	2 6.7%
Other	3 11.5%	1 25%	4 13.3%
Unknown	1 3.8%	1 25%	2 6.7%
Systemic treatment (Count of Participants)
None	13 50%	3 75%	16 53.3%
Chemotherapy	7 26.9%	1 25%	8 26.7%
Hormone therapy	4 15.4%	0 0%	4 13.3%
Bisphosphonate only	2 7.7%	0 0%	2 6.7%
Radiotherapy dose (Count of Participants)
8 Gy in 1 fraction	16 61.5%	4 100%	20 66.7%
20 Gy in 5 fractions	6 23.1%	0 0%	6 20%
30 Gy in 10 fractions	4 15.4%	0 0%	4 13.3%

Outcome Measures

1. Primary Outcome

Title	Efficacy for the Prevention/Rescue of Radiation-induced Nausea and Vomiting.
Description	The primary objectives are to examine the efficacy for the prevention/rescue of Acute and Delayed Phase radiation-induced nausea and vomiting (RINV) in patients undergoing single or multiple fraction, emetogenic palliative radiation therapy for painful bone metastases. Complete control: No increase in emetic episodes or increase in use of rescue medication (for secondary prophylaxis) following radiation treatment, compared to the number of incidences at baseline. Partial control: Increase of 2 or fewer emetic episodes from baseline and no use of rescue antiemetic medication during or after radiotherapy. Uncontrolled: Increase of three or more emetic episodes or use of antiemetic rescue medication.
Time Frame	Day 0 - Day 10

Outcome Measure Data

Analysis Population Description

The results here encompass the primary outcome measure "the proportion of patients with complete prophylaxis and partial control", which is repeated in the secondary outcome. The secondary outcome "Time to nausea, vomiting and/or use of rescue medication" is unavailable due to the data not being collected/analysed.

Arm/Group Title	Primary Prophylaxis	Secondary Prophylaxis
Arm/Group Description	Patients had no nausea or vomiting at baseline.	Patients had nausea or vomiting at baseline.
Measure Participants	28	4
Complete control	21 80.8%	4 100%
Partial control	2 7.7%	0 0%
Uncontrolled	3 11.5%	0 0%
Complete control	25 96.2%	2 50%
Partial control	1 3.8%	0 0%
Uncontrolled	2 7.7%	0 0%
Complete control	18 69.2%	2 50%
Partial control	1 3.8%	0 0%
Uncontrolled	7 26.9%	2 50%
Complete control	21 80.8%	1 25%
Partial control	0 0%	0 0%
Uncontrolled	7 26.9%	1 25%
Complete control	17 65.4%	2 50%
Partial control	1 3.8%	0 0%
Uncontrolled	8 30.8%	2 50%
Complete control	21 80.8%	1 25%
Partial control	0 0%	0 0%
Uncontrolled	7 26.9%	1 25%

2. Other Pre-specified Outcome

Title	The European Organization for Research and Treatment of Cancer Quality of LIfe Questionnaire - C15 Palliative (C15-PAL), From Day 1-5 of Treatment.
Description	Quality of life as measured by the EORTC QLQ-C15-PAL. For multiple fractions of radiotherapy, the questionnaire will be administered on Day 5 and 10 during treatment when applicable. Since the number of secondary prophylaxis patients was small (n=4), quality of life (QOL) analysis was done with two arms combined. Questions on the C15-PAL were scored on a scale of 0-100, with 0 representing no symptoms but low level of functioning and 100 representing severe symptoms and high degree of functioning.
Time Frame	Day 0-5 during treatment

Outcome Measure Data

Analysis Population Description

The primary prophylaxis arm and secondary prophylaxis arm patients were combined and analysed together, because the secondary prophylaxis arm had only 4 patients, which was too low to draw any meaningful conclusions.

Arm/Group Title	C15-PAL Results
Arm/Group Description	C15-PAL results
Measure Participants	30
Pain	50.6 (31.0)
Dyspnea	24.1 (25.0)
Insomnia	34.5 (33.9)
Appetite loss	36.8 (36.0)
Constipation	27.6 (34.6)
Overall quality of life	47.7 (24.3)
Physical functioning	49.0 (36.2)
Fatigue	54.8 (34.4)
Nausea/vomiting	5.75 (19.0)
Emotional functioning	69.2 (25.8)

3. Other Pre-specified Outcome

Title	The European Organization for Research and Treatment of Cancer Quality of LIfe Questionnaire - C15 Palliative (C15-PAL) on Day 6-10 of Treatment.
Description	Quality of life as measured by the EORTC QLQ-C15-PAL. For multiple fractions of radiotherapy, the questionnaire will be administered on Day 5 and 10 during treatment when applicable. Since the number of secondary prophylaxis patients was small (n=4), quality of life (QOL) analysis was done with two arms combined. Questions on the C15-PAL were scored on a scale of 0-100, with 0 representing no symptoms but low level of functioning and 100 representing severe symptoms and high degree of functioning.
Time Frame	Day 6-10 of treatment

Outcome Measure Data

Analysis Population Description

Combined patients from primary prophylaxis and secondary prophylaxis arms, due to the low number of patients in the secondary prophylaxis arm (n=4).

Arm/Group Title	C15-PAL Results
Arm/Group Description	C15-PAL results
Measure Participants	30
Pain	49.4 (32.5)
Dyspnea	25.9 (31.1)
Insomnia	44.4 (33.3)
Appetite loss	38.3 (36.6)
Constipation	27.1 (34.6)
Overall quality of life	47.7 (24.3)
Physical functioning	49.0 (36.2)
Fatigue	54.8 (34.4)
Nausea/vomiting	5.75 (19.0)
Emotional functioning	69.2 (25.8)

4. Other Pre-specified Outcome

Title	Functional Living Index-emesis (FLIE) at Day 3, Using Questions 2-9, 11-18 (Q1/Q10 Refer to Nausea/Vomiting and Therefore Are Part of Primary Objectives)
Description	Since the number of secondary prophylaxis patients was small (n=4), quality of life (QOL) analysis was done with two arms combined. Questions on the FLIE are reported from 1-7, with "1" being no symptoms and "not at all" for interference with life, and "7" being "a great deal" of symptom and interference with life. Q1-9 are for nausea (N). Q 10-18 are for vomiting (V). All questions refer to "during the past 3 days". Q1/10: How much N/V have you had? Q2/11: Has N/V affected your ability to maintain usual recreation or leisure activities? Q3/12: Has N/V affected your ability to make a meal or do minor household repairs? Q4/13: How much has N/V affected your ability to enjoy a meal? Q5/14: How much has N/V affected your ability to enjoy liquid refreshment? Q6/15: How much has N/V affected your willingness to see and spend time with family/friends? Q7/16: Has N/V affected your daily functioning? Q8/17: Degree your N/V imposed hardship on you? Q9/18: Degree on your family?
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

Since the number of secondary prophylaxis patients was small (n=4), quality of life (QOL) analysis was done with two arms combined.

Arm/Group Title	C15-PAL Results
Arm/Group Description	C15-PAL results
Measure Participants	30
Q2 nausea affecting leisure activities	1.31 (0.43)
Q3 nausea affecting ability to do house work	1.21 (0.81)
Q4 nausea affecting enjoyment of meals	1.40 (1.19)
Q5 nausea affecting enjoyment of refreshments	1.17 (0.46)
Q6 nausea affecting spending time with loved ones	1.10 (0.40)
Q7 nausea affecting daily functioning	1.13 (0.43)
Q8 nausea imposing personal hardship	1.20 (0.55)
Q9 nausea imposing hardship on others	1.13 (0.51)
Q11 vomiting affecting leisure activities	1.03 (0.18)
Q12 vomiting affecting ability to do house work	1 (0)
Q13 vomiting affecting enjoyment of meals	1.03 (0.18)
Q14 vomiting affecting enjoyment of refreshments	1.03 (0.18)
Q15 vomiting affecting spending time with loved on	1.03 (0.18)
Q16 vomiting affecting daily functioning	1.03 (0.19)
Q17 vomiting imposing personal hardship	1.07 (0.25)
Q18 vomiting imposing hardship on others	1.03 (0.18)

5. Other Pre-specified Outcome

Title	Functional Living Index-emesis (FLIE) at Day 7, Using Questions 2-9, 11-18 (Q1/Q10 Refer to Nausea/Vomiting and Therefore Are Part of Primary Objectives)
Description	Since the number of secondary prophylaxis patients was small (n=4), quality of life (QOL) analysis was done with two arms combined. Questions on the FLIE are reported from 1-7, with "1" being no symptoms and "not at all" for interference with life, and "7" being "a great deal" of symptom and interference with life. Q1-9 are for nausea (N). Q 10-18 are for vomiting (V). All questions refer to "during the past 3 days". Q1/10: How much N/V have you had? Q2/11: Has N/V affected your ability to maintain usual recreation or leisure activities? Q3/12: Has N/V affected your ability to make a meal or do minor household repairs? Q4/13: How much has N/V affected your ability to enjoy a meal? Q5/14: How much has N/V affected your ability to enjoy liquid refreshment? Q6/15: How much has N/V affected your willingness to see and spend time with family/friends? Q7/16: Has N/V affected your daily functioning? Q8/17: Degree your N/V imposed hardship on you? Q9/18: Degree on your family?
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

Since the number of secondary prophylaxis patients was small (n=4), quality of life (QOL) analysis was done with two arms combined.

Arm/Group Title	C15-PAL Results
Arm/Group Description	C15-PAL results
Measure Participants	30
Q2 nausea affecting leisure activities	1.23 (0.82)
Q3 nausea affecting ability to do house work	1.19 (0.69)
Q4 nausea affecting enjoyment of meals	1.37 (1.01)
Q5 nausea affecting enjoyment of refreshments	1.15 (0.60)
Q6 nausea affecting spending time with loved ones	1.19 (0.56)
Q7 nausea affecting daily functioning	1.19 (0.56)
Q8 nausea imposing personal hardship	1.26 (0.71)
Q9 nausea imposing hardship on others	1.22 (0.80)
Q11 vomiting affecting leisure activities	1.19 (0.68)
Q12 vomiting affecting ability to do house work	1.19 (0.68)
Q13 vomiting affecting enjoyment of meals	1.30 (1.2)
Q14 vomiting affecting enjoyment of refreshments	1.30 (1.2)
Q15 vomiting affecting spending time with loved on	1.15 (0.60)
Q16 vomiting affecting daily functioning	1.19 (0.68)
Q17 vomiting imposing personal hardship	1.19 (0.56)
Q18 vomiting imposing hardship on others	1.12 (0.43)

Adverse Events

Arm/Group Title	Ondissolve
Arm/Group Description	Patients will take Ondissolve (8mg) on the day of the radiation treatment at least one hour prior to treatment and repeat approximately 6-8 hours later in the day (bid). For patients who are being treated with 20Gy in 5 fractions, or 30 Gy in 10 fractions, this group will take Ondissolve twice (bid) on each day of treatment, at least 1 hour prior to treatment and also on weekends or holidays in between treatment. Ondissolve: Patients will take Ondissolve (8mg) on the day of the radiation treatment at least one hour prior to treatment and repeat approximately 6-8 hours later in the day (bid). For patients who are being treated with 20Gy in 5 fractions, or 30 Gy in 10 fractions, this group will take Ondissolve twice (bid) on each day of treatment, at least 1 hour prior to treatment and also on weekends or holidays in between treatment. Palliative Radiation Therapy: Patient will receive palliative radiation therapy considered emetogenic for bone metastases.
All Cause Mortality
	Ondissolve
	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)
Serious Adverse Events
	Ondissolve
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Other (Not Including Serious) Adverse Events
	Ondissolve
	Affected / at Risk (%)	# Events
Total	0/30 (0%)

Limitations/Caveats

Small sample size, with most patients having no pre-existing nausea and vomiting. finding need to be confirmed in larger study and perhaps in a randomized trial comparing oral pill formation with ondansetron RDF in the prophylaxis of RINV.

More Information

Certain Agreements

Principal Investigators are NOT 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.