Oral Ondansetron Versus Transdermal Granisetron (Sancuso) for Women With Cervical, Endometrial or Vaginal Cancer Receiving Pelvic Chemoradiation

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01536392
• Collaborator: Sancuso (Other)
• Enrollment: 76
• Locations: 2
• Arms: 2
• Actual Duration (Months): 91.1
• Patients Per Site: 38
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to compare granisetron (when given through a patch) to ondansetron (when taken by mouth) for reducing nausea and vomiting in women with cervical, endometrial, or vaginal cancer having chemoradiation.

Granisetron and ondansetron are designed to help reduce nausea and vomiting.

Condition or Disease	Intervention/Treatment	Phase
Cancer of the Cervix	Drug: Granisetron; Drug: Ondansetron; Behavioral: Questionnaires; Behavioral: Study Drug Diary	Phase 3

Detailed Description

Study Groups:

If you agree to take part in this study, and you are among the first 40 participants, you will have an equal chance of being in either group. If you enroll after that, you will have a higher chance (51%-100%) of being assigned to the group that had better results.

• If you are in Group 1, you will receive granisetron by patch.

• If you are in Group 2, you will receive ondansetron by mouth.

Study Drug Administration:

If you are in Group 1, you will receive ondansetron by vein at your first visit only, which is standard of care. Then, you will receive cisplatin by vein over about 1 hour as part of the chemoradiation. A granisetron patch will then be placed on your skin before the chemotherapy . The patch will be replaced every 7 days before the chemotherapy.

If you are in Group 2, you will receive ondansetron by vein before cisplatin. Then, you will receive cisplatin by vein over about 1 hour. Then you will take ondansetron by mouth with a cup of water (8 ounces) 3 times a day for 3 days. Ondansetron is a tablet that you can take with or without food and is best taken at least 30 minutes before eating.

Both groups will be given a study drug diary to record the times that you take the study drugs. You will also record any nausea or vomiting that you may have. You should bring the diary to each study visit. You should also bring your study drug bottles/packages to each study visit.

Study Visits:

The visits for this study will be at the same time as your chemoradiation therapy visits over 5 weeks.

You will complete 3 questionnaires at your study visits and then again 1 week after the last chemotherapy. The last questionnaires will be completed by phone. The questionnaires ask about how easy or difficult it is to use your assigned study drug, your level of nausea and vomiting, and your quality of life. It should take about 5 minutes to complete these questionnaires each time.

Length of Treatment:

You may continue using the study drug up to 5 weeks during your chemoradiation treatment. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over when you have completed 5 weeks of chemoradiation treatments.

This is an investigational study. Both granisetron and ondansetron are FDA approved and commercially available for the treatment of nausea and vomiting. It is investigational to compare these drugs administered in different ways.

Up to 150 patients will take part in this study. Up to 120 participants will take part at MD Anderson. Up to 30 will be enrolled at the Harris Health System.

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Oral Ondansetron Versus Transdermal Granisetron (Sancuso) for Women With Cervical, Endometrial or Vaginal Cancer Receiving Pelvic Chemoradiation
• Actual Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Oct 3, 2019
• Actual Study Completion Date: Oct 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Granisetron Group A: 34.3 mg of granisetron formulated in transdermal patch replaced every 7 days. Transdermal patch placed/replaced prior to the intravenous (IV) infusion of cisplatin. At cycle 1, participants receive IV granisetron prior to IV cisplatin and prior to administration of transdermal patch.	Drug: Granisetron; 34.3 mg of granisetron formulated in a transdermal patch replaced every 7 days. At cycle 1, participants receive granisetron by vein prior to IV cisplatin and prior to administration of transdermal patch.; Behavioral: Questionnaires; Completion of 3 questionnaires at study visits taking about 5 minutes each time.; Other Names: Surveys ; Behavioral: Study Drug Diary; Study drug diary to record times that study drugs taken, and to record any nausea or vomiting experienced.
Experimental: Ondansetron Group B: 8 mg of ondansetron orally thrice daily starting with cisplatin administration and continued for 72 hours after chemotherapy infusion.	Drug: Ondansetron; 8 mg of ondansetron by mouth three times a day starting with cisplatin administration and continued for 72 hours after chemotherapy infusion.; Other Names: Zofran ; Behavioral: Questionnaires; Completion of 3 questionnaires at study visits taking about 5 minutes each time.; Other Names: Surveys ; Behavioral: Study Drug Diary; Study drug diary to record times that study drugs taken, and to record any nausea or vomiting experienced.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Response Rate to Anti-Emetic Therapy Days 4-7 Each Chemotherapy Cycle [Baseline, up to 7 days post-chemotherapy, through 5 cycles of chemotherapy measured each cycle, an average of 6 weeks]

   Response defined as no emetic or retching episodes and no rescue medication use during late onset phase (4-7 days post-chemotherapy) measured each cycle. Responses tabulated to 4 items of Morisky Medication Adherence measure for each treatment group by cycle of therapy. Elements summarized of Morrow Assessment of Nausea and Emesis and for pill counts/compliance for each treatment group by cycle of therapy. Descriptive statistics summarize total scores for Osoba Module, used to measure effect of nausea and vomiting on quality of life, for each treatment group by cycle of therapy. Osoba Nausea and Emesis Module; higher scores indicate worse quality of life. Morisky Medication Adherence Scale. Higher scores indicate higher compliance. Morisky Medication Adherence Scale is Yes=0 and No=1 , zero is the lowest level of medication adherence, and 4 is the highest level of medication adherence.

Secondary Outcome Measures

1. Percentage of Participants With Response Rate to Anti Emetic Therapy 0-24 Hours Each Chemotherapy Cycle [Baseline, up to 24 hours post-chemotherapy, through 5 cycles of chemotherapy measured each cycle, an average of 6 weeks]

   The response rates to anti-emetic therapy (no emetic or retching episodes and no rescue medication use) in the acute (0-24 hours) phase. Responses tabulated to 4 items of Morisky Medication Adherence measure for each treatment group by cycle of therapy. Elements summarized of Morrow Assessment of Nausea and Emesis and for pill counts/compliance for each treatment group by cycle of therapy. Descriptive statistics summarize total scores for Osoba Module, used to measure effect of nausea and vomiting on quality of life, for each treatment group by cycle of therapy. Osoba Nausea and Emesis Module; higher scores indicate worse quality of life. Morisky Medication Adherence Scale. Higher scores indicate higher compliance. Morisky Medication Adherence Scale is Yes=0 and No=1 , zero is the lowest level of medication adherence, and 4 is the highest level of medication adherence.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Women with cervical, endometrial or vaginal cancer dispositioned to receive primary or postoperative adjuvant pelvic radiation therapy with concurrent cisplatin administration.

2. Women must be at least 18 years of age.

3. Women must be able to read English or Spanish at a sixth grade level.

4. Women with childbearing potential must have a negative pregnancy test within 1 week of starting chemoradiation therapy.

Exclusion Criteria:

1. Women with cervical, endometrial or vaginal cancer who are receiving chemotherapy and/or radiation therapy for recurrent disease.

2. Women with cervical, endometrial, or vaginal cancer who are receiving extended field radiation therapy.

3. Women with cervical, endometrial or vaginal cancer who are receiving chemotherapy and/or radiation therapy in a palliative setting.

4. Women with cervical, endometrial, or vaginal cancer who have already received their first dose of chemotherapy or radiation for more than 7 days prior to starting chemotherapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lyndon B. Johnson General Hospital	Houston	Texas	United States	77026
2	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Sancuso

Investigators

• Principal Investigator: Michael M. Frumovitz, MD, MPH, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 12, 2015

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01536392
• Other Study ID Numbers: 2011-1107; NCI-2012-00221
• First Posted: Feb 22, 2012
• Last Update Posted: Jun 11, 2021
• Last Verified: May 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Cancer of the Cervix; Anti-emetic therapy; Granisetron; Transdermal patch; Ondansetron; Zofran; Questionnaires; Surveys; Study Drug Diary; Nausea and Vomiting
• Additional relevant MeSH terms: Vaginal Neoplasms; Uterine Cervical Neoplasms; Ondansetron; Granisetron

Study Results

Participant Flow

Recruitment Details	Recruitment period: March 2012 until June 2016. All the recruitment was done in a medical clinic setting.
Pre-assignment Detail	76 participants signed consent, 1 participant did not receive treatment due to the study closure.

Arm/Group Title	Arm 1: Transdermal Granisetron	Arm 2: Oral Ondansetron
Arm/Group Description	8 mg ondansetron given IV prior to Cycle 1 of Cisplatin then 34.3 mg granisetron patch applied and then reapplied every 7 days prior to Cycles 2-5 of Cisplatin.	8 mg ondansetron given IV prior to Cycles 1-5 then 8 mg oral ondansetron every 8 hours for 72 hours following each Cisplatin and PRN in-between cycles.
Period Title: Overall Study
STARTED	41	34
COMPLETED	28	19
NOT COMPLETED	13	15

Baseline Characteristics

Arm/Group Title	Arm 1: Transdermal Granisetron	Arm 2: Oral Ondansetron	Total
Arm/Group Description	8 mg ondansetron given IV prior to Cycle 1 of Cisplatin then 34.3 mg granisetron patch applied and then reapplied every 7 days prior to Cycles 2-5 of Cisplatin.	8 mg ondansetron given IV prior to Cycles 1-5 then 8 mg oral ondansetron every 8 hours for 72 hours following each Cisplatin and PRN in-between cycles.	Total of all reporting groups
Overall Participants	41	34	75
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	37 90.2%	31 91.2%	68 90.7%
>=65 years	4 9.8%	3 8.8%	7 9.3%
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	45	51	49
Sex: Female, Male (Count of Participants)
Female	41 100%	34 100%	75 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 24.4%	6 17.6%	16 21.3%
Not Hispanic or Latino	18 43.9%	14 41.2%	32 42.7%
Unknown or Not Reported	13 31.7%	14 41.2%	27 36%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.4%	1 2.9%	2 2.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 12.2%	4 11.8%	9 12%
White	33 80.5%	29 85.3%	62 82.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 4.9%	0 0%	2 2.7%
Region of Enrollment (participants) [Number]
United States	41 100%	34 100%	75 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Response Rate to Anti-Emetic Therapy Days 4-7 Each Chemotherapy Cycle
Description	Response defined as no emetic or retching episodes and no rescue medication use during late onset phase (4-7 days post-chemotherapy) measured each cycle. Responses tabulated to 4 items of Morisky Medication Adherence measure for each treatment group by cycle of therapy. Elements summarized of Morrow Assessment of Nausea and Emesis and for pill counts/compliance for each treatment group by cycle of therapy. Descriptive statistics summarize total scores for Osoba Module, used to measure effect of nausea and vomiting on quality of life, for each treatment group by cycle of therapy. Osoba Nausea and Emesis Module; higher scores indicate worse quality of life. Morisky Medication Adherence Scale. Higher scores indicate higher compliance. Morisky Medication Adherence Scale is Yes=0 and No=1 , zero is the lowest level of medication adherence, and 4 is the highest level of medication adherence.
Time Frame	Baseline, up to 7 days post-chemotherapy, through 5 cycles of chemotherapy measured each cycle, an average of 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Transdermal Granisetron	Arm 2: Oral Ondansetron
Arm/Group Description	8 mg ondansetron given IV prior to Cycle 1 of Cisplatin then 34.3 mg granisetron patch applied and then reapplied every 7 days prior to Cycles 2-5 of Cisplatin.	8 mg ondansetron given IV prior to Cycles 1-5 then 8 mg oral ondansetron every 8 hours for 72 hours following each Cisplatin and PRN in-between cycles.
Measure Participants	41	34
Number (95% Confidence Interval) [percentage of participants]	49.8 121.5%	39.7 116.8%

2. Secondary Outcome

Title	Percentage of Participants With Response Rate to Anti Emetic Therapy 0-24 Hours Each Chemotherapy Cycle
Description	The response rates to anti-emetic therapy (no emetic or retching episodes and no rescue medication use) in the acute (0-24 hours) phase. Responses tabulated to 4 items of Morisky Medication Adherence measure for each treatment group by cycle of therapy. Elements summarized of Morrow Assessment of Nausea and Emesis and for pill counts/compliance for each treatment group by cycle of therapy. Descriptive statistics summarize total scores for Osoba Module, used to measure effect of nausea and vomiting on quality of life, for each treatment group by cycle of therapy. Osoba Nausea and Emesis Module; higher scores indicate worse quality of life. Morisky Medication Adherence Scale. Higher scores indicate higher compliance. Morisky Medication Adherence Scale is Yes=0 and No=1 , zero is the lowest level of medication adherence, and 4 is the highest level of medication adherence.
Time Frame	Baseline, up to 24 hours post-chemotherapy, through 5 cycles of chemotherapy measured each cycle, an average of 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Transdermal Granisetron	Arm 2: Oral Ondansetron
Arm/Group Description	8 mg ondansetron given IV prior to Cycle 1 of Cisplatin then 34.3 mg granisetron patch applied and then reapplied every 7 days prior to Cycles 2-5 of Cisplatin.	8 mg ondansetron given IV prior to Cycles 1-5 then 8 mg oral ondansetron every 8 hours for 72 hours following each Cisplatin and PRN in-between cycles.
Measure Participants	41	34
Number (95% Confidence Interval) [percentage of participants]	49.8 121.5%	39.7 116.8%

Adverse Events

Time Frame	Baseline through 7 days for each chemotherapy cycle, an average of 6 weeks
Arm/Group Title	Arm 1: Transdermal Granisetron		Arm 2: Oral Ondansetron
Arm/Group Description	8 mg ondansetron given IV prior to Cycle 1 of Cisplatin then 34.3 mg granisetron patch applied and then reapplied every 7 days prior to Cycles 2-5 of Cisplatin.		8 mg ondansetron given IV prior to Cycles 1-5 then 8 mg oral ondansetron every 8 hours for 72 hours following each Cisplatin and PRN in-between cycles.
All Cause Mortality
	Arm 1: Transdermal Granisetron		Arm 2: Oral Ondansetron
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/34 (0%)
Serious Adverse Events
	Arm 1: Transdermal Granisetron		Arm 2: Oral Ondansetron
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/41 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Arm 1: Transdermal Granisetron		Arm 2: Oral Ondansetron
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/41 (36.6%)		12/34 (35.3%)
Gastrointestinal disorders
Constipation	8/41 (19.5%)		6/34 (17.6%)
Diarrhea	9/41 (22%)		3/34 (8.8%)
Nausea	15/41 (36.6%)		12/34 (35.3%)
General disorders
Fatigue	7/41 (17.1%)		10/34 (29.4%)

Limitations/Caveats

[Not Specified]

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.