Intravenous Palonosetron With Radiotherapy and Concomitant Temozolomide

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00900757
• Collaborator: Eisai Inc. (Industry)
• Enrollment: 57
• Location: 1
• Arm: 1
• Duration (Months): 40
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

1. Purpose and objective:

2. To determine the safety and tolerability of palonosetron in the prevention of radiation induced nausea and vomiting (RINV) in primary glioma patients receiving radiation (RT) and concomitant temozolomide (TMZ).

3. To determine the efficacy of palonosetron in primary glioma patients receiving six weeks of RT and concomitant TMZ

4. To evaluate the effect s of palonosetron on the quality of life of primary glioma patients receiving six weeks of RT and Concomitant TMZ.

5. Study activities and Population group: We will conduct a phase II single arm trial of Palonosetron (PALO) for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ). All eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks. Forty subjects with gliomas will participate.

6. Data analysis and risk/safety issues: The frequency of toxicity will be summarized by type and the most severe grade experienced. The complete response rate, defined as the proportion of patients with no emetic episode or use of rescue medication while receiving radiation and concomitant temozolomide, will be estimated with a 95% confidence interval.

Condition or Disease	Intervention/Treatment	Phase
Malignant Glioma	Drug: Palonosetron (PALO)	Phase 2

Detailed Description

We will conduct a phase II single arm trial of Palonosetron (PALO) for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ). All eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron approximately 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks. After the start of radiation the type of rescue medication will be up to the investigator's discretion (however given the results of recent published phase II study by Navari et. al. we recommend using olanzapine for rescue medication). All patients will be given written informed consent.

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Phase II Study to Evaluate the Efficacy and Safety of Intravenous Palonosetron in Primary Glioma Patients Receiving Standard Radiotherapy and Concomitant Temozolomide
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Palonosetron Single Arm trial of Palonosetron for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ)

Drug: Palonosetron (PALO); Eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks.; Other Names: Aloxi

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of Palonosetron as Determined by the Number of Participants Who Experience Unacceptable Toxicity [6 weeks]

   The number of participants with unacceptable toxicity defined as ≥grade 3, non-hematologic toxicities that are possibly, probably or definitely related to the study regimen.

Secondary Outcome Measures

1. Complete Response [6 weeks]

   The percentage of participants with a complete response defined as no emetic episode or use of rescue medication while receiving radiation (XRT) and concomitant temozolomide (TMZ).

2. Change in the Functional Living Index - Emesis (FLIE) Score From Baseline to Each Week of Radiation (XRT) and Temozolomide (TMZ) Treatment [6 weeks]

   The FLIE is a 18-item validated questionnaire for assessing the effects of chemotherapy-induced nausea and emesis on quality of life and daily functioning. The raw score range is 18-126 with higher scores indicating better quality of life. For each week of XRT and TMZ, the change from baseline was calculated by subtracting the baseline score from the mean of the day 1, 3 and 6 scores. A negative change represents worsening in quality of life due to nausea and emesis.

3. Percentage of Participants With a Osoba Nausea Module Maximum Standardized Score of Zero for Each Week of Radiation (XRT) and Temozolomide (TMZ) [6 weeks]

   Percentage of participants with a Osoba nausea module maximum standardized score of zero for each week of radiation (XRT) and Temozolomide (TMZ). The Osoba nausea module is a 5-item questionnaire assessing the effect of nausea on quality of life and daily functioning. Raw scores range from 5-20 and have been converted to standardized scores (0-100) using the formula: std_score = round((raw_score - 5) * 6.66). Lower scores indicate better quality fo life. The maximum standardized score of all nausea scores collected during the week (days 1, 3 and 6) was used for this outcome.

4. Percentage of Participants With a Osoba Vomiting/Retching Module Maximum Standardized Score of Zero for Each Week of Radiation (XRT) and Temozolomide (TMZ) [6 weeks]

   Percentage of participants with a Osoba vomiting/retching module maximum standardized score of zero for each week of radiation (XRT) and Temozolomide (TMZ). The Osoba vomiting/retching module is a 5-item questionnaire assessing the effect of vomiting/retching on quality of life and daily functioning. Raw scores range from 5-20 and have been converted to standardized scores (0-100) using the formula: std_score = round((raw_score - 5) * 6.66). Lower scores indicate better quality fo life. The maximum standardized score of all vomiting/retching scores collected during the week (days 1, 3 and 6) was used for this outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age ≥ 18 years;

• Karnofsky ≥ 60%;

• Hematocrit > 29%, absolute neutrophil count (ANC) > 1,000 cells/*1, platelets > 100,000 cells/*I;

• Serum creatinine < 1.4 mg/dl; serum glutamate oxaloacetate transaminase (SGOT) and bilirubin < 1.5 times upper limit of normal;

• For patients on corticosteroids, they must have been on a stable dose for 1 week prior to entry, and the dose should not be escalated over entry dose level, if clinically possible;

• Signed informed consent approved by the Institutional Review Board prior to patient entry;

• If sexually active, patients w8ill take contraceptive measures for the duration of the treatments.

Exclusion Criteria:

• Pregnancy or breastfeeding;

• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids;

• Inability or unwillingness to cooperate with the study procedures;

• Prophylactic medication for the prevention of nausea and vomiting 24 hours prior to the start of radiation therapy through the full course of radiation therapy is prohibited, with the exception of the study drug. Corticosteroids will be allowed for treatment of cerebral swelling. Rescue medication for treatment of nausea and vomiting is permitted after radiation therapy at the discretion of the investigator. The agent, dose, and time of administration will be recorded in the patient diary;

• Previous participation in any clinical trial involving palonosetron;

• Any vomiting, retching, or NCI Common Toxicity Criteria version 3.0 grade 2-4 nausea in the 24 hours preceding radiation and chemotherapy;

• Ongoing vomiting from any organic etiology;

• Will receive radiotherapy of upper abdomen within one week prior to or during the study;

• Received palonosetron within 14 days prior to study enrollment;

• Prior and Concomitant Medications for Prevention/Treatment of Nausea and Vomiting;

• Prior and Concomitant Cancer Chemotherapy and Radiotherapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Preston Robert Tisch Brain Tumor Center at Duke	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University
• Eisai Inc.

Investigators

• Principal Investigator: Mary Lou Affronti, RN, MSN, ANP, Duke Health

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00900757
• Other Study ID Numbers: Pro00015573
• First Posted: May 13, 2009
• Last Update Posted: Aug 28, 2019
• Last Verified: Mar 1, 2014

• Keywords provided by Duke University: Primary Glioma; Palonosetron; Standard Radiotherapy; Temozolomide
• Additional relevant MeSH terms: Glioma; Palonosetron

Study Results

Participant Flow

Arm/Group Title	Palonosetron
Arm/Group Description	Single Arm trial of Palonosetron for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ) Palonosetron (PALO): Eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks.
Period Title: Overall Study
STARTED	57
COMPLETED	38
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	Palonosetron
Arm/Group Description	Single Arm trial of Palonosetron for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ) Palonosetron (PALO): Eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks.
Overall Participants	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.9 (9.5)
Sex: Female, Male (Count of Participants)
Female	21 55.3%
Male	17 44.7%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability of Palonosetron as Determined by the Number of Participants Who Experience Unacceptable Toxicity
Description	The number of participants with unacceptable toxicity defined as ≥grade 3, non-hematologic toxicities that are possibly, probably or definitely related to the study regimen.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palonosetron
Arm/Group Description	Single Arm trial of Palonosetron for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ) Palonosetron (PALO): Eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks.
Measure Participants	38
Number [participants]	5 13.2%

2. Secondary Outcome

Title	Complete Response
Description	The percentage of participants with a complete response defined as no emetic episode or use of rescue medication while receiving radiation (XRT) and concomitant temozolomide (TMZ).
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palonosetron
Arm/Group Description	Single Arm trial of Palonosetron for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ) Palonosetron (PALO): Eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks.
Measure Participants	38
Week 1 of XRT and TMZ (n=38)	74 194.7%
Week 2 of XRT and TMZ (n=38)	79 207.9%
Week 3 of XRT and TMZ (n=38)	76 200%
Week 4 of XRT and TMZ (n=38)	74 194.7%
Week 5 of XRT and TMZ (n=36)	67 176.3%
Week 6 of XRT and TMZ (n=34)	71 186.8%
Overall (across weeks 1-6 of XRT and TMZ) (N=34)	44 115.8%

3. Secondary Outcome

Title	Change in the Functional Living Index - Emesis (FLIE) Score From Baseline to Each Week of Radiation (XRT) and Temozolomide (TMZ) Treatment
Description	The FLIE is a 18-item validated questionnaire for assessing the effects of chemotherapy-induced nausea and emesis on quality of life and daily functioning. The raw score range is 18-126 with higher scores indicating better quality of life. For each week of XRT and TMZ, the change from baseline was calculated by subtracting the baseline score from the mean of the day 1, 3 and 6 scores. A negative change represents worsening in quality of life due to nausea and emesis.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palonosetron
Arm/Group Description	Single Arm trial of Palonosetron for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ) Palonosetron (PALO): Eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks.
Measure Participants	38
Week 1 of XRT and TMZ (n=38)	-3.3
Week 2 of XRT and TMZ (n=38)	-2.7
Week 3 of XRT and TMZ (n=38)	-1.9
Week 4 of XRT and TMZ (n=38)	-3.9
Week 5 of XRT and TMZ (n=36)	-5.5
Week 6 of XRT and TMZ (n=34)	-4.1

4. Secondary Outcome

Title	Percentage of Participants With a Osoba Nausea Module Maximum Standardized Score of Zero for Each Week of Radiation (XRT) and Temozolomide (TMZ)
Description	Percentage of participants with a Osoba nausea module maximum standardized score of zero for each week of radiation (XRT) and Temozolomide (TMZ). The Osoba nausea module is a 5-item questionnaire assessing the effect of nausea on quality of life and daily functioning. Raw scores range from 5-20 and have been converted to standardized scores (0-100) using the formula: std_score = round((raw_score - 5) * 6.66). Lower scores indicate better quality fo life. The maximum standardized score of all nausea scores collected during the week (days 1, 3 and 6) was used for this outcome.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palonosetron
Arm/Group Description	Single Arm trial of Palonosetron for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ) Palonosetron (PALO): Eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks.
Measure Participants	38
Week 1 of XRT and TMZ (n=38)	76 200%
Week 2 of XRT and TMZ (n=38)	79 207.9%
Week 3 of XRT and TMZ (n=38)	79 207.9%
Week 4 of XRT and TMZ (n=38)	79 207.9%
Week 5 of XRT and TMZ (n=35)	71 186.8%
Week 6 of XRT and TMZ (n=34)	79 207.9%

5. Secondary Outcome

Title	Percentage of Participants With a Osoba Vomiting/Retching Module Maximum Standardized Score of Zero for Each Week of Radiation (XRT) and Temozolomide (TMZ)
Description	Percentage of participants with a Osoba vomiting/retching module maximum standardized score of zero for each week of radiation (XRT) and Temozolomide (TMZ). The Osoba vomiting/retching module is a 5-item questionnaire assessing the effect of vomiting/retching on quality of life and daily functioning. Raw scores range from 5-20 and have been converted to standardized scores (0-100) using the formula: std_score = round((raw_score - 5) * 6.66). Lower scores indicate better quality fo life. The maximum standardized score of all vomiting/retching scores collected during the week (days 1, 3 and 6) was used for this outcome.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palonosetron
Arm/Group Description	Single Arm trial of Palonosetron for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ) Palonosetron (PALO): Eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks.
Measure Participants	38
Week 1 of XRT and TMZ (n=38)	87 228.9%
Week 2 of XRT and TMZ (n=38)	89 234.2%
Week 3 of XRT and TMZ (n=38)	100 263.2%
Week 4 of XRT and TMZ (n=38)	92 242.1%
Week 5 of XRT and TMZ (n=35)	89 234.2%
Week 6 of XRT and TMZ (n=34)	97 255.3%

Adverse Events

Time Frame	6 weeks
Adverse Event Reporting Description	The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Arm/Group Title	Palonosetron
Arm/Group Description	Single Arm trial of Palonosetron for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ) Palonosetron (PALO): Eligible patients should receive a planned total dose of 54-60 GY of radiation and 75 mg/m2 of daily temozolomide for a total of six weeks of treatment. For each week of radiation patients will receive a single 0.25 mg intravenous dose of palonosetron 30 minutes before each week of radiation fraction. This schedule will be repeated for each week of radiation for a total of 6 weeks.
All Cause Mortality
	Palonosetron
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Palonosetron
	Affected / at Risk (%)	# Events
Total	5/38 (13.2%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify	1/38 (2.6%)
Cardiac disorders
Atrial fibrillation	1/38 (2.6%)
General disorders
Edema face	1/38 (2.6%)
Injury, poisoning and procedural complications
Vascular access complication	1/38 (2.6%)
Nervous system disorders
Headache	1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/38 (2.6%)
Pneumonitis	1/38 (2.6%)
Vascular disorders
Thromboembolic event	1/38 (2.6%)
Other (Not Including Serious) Adverse Events
	Palonosetron
	Affected / at Risk (%)	# Events
Total	36/38 (94.7%)
Blood and lymphatic system disorders
Anemia	2/38 (5.3%)
Eye disorders
Blurred vision	15/38 (39.5%)
Gastrointestinal disorders
Constipation	21/38 (55.3%)
Diarrhea	8/38 (21.1%)
Gastrointestinal disorders - Other, specify	1/38 (2.6%)
Ileus	1/38 (2.6%)
Mucositis oral	8/38 (21.1%)
Nausea	16/38 (42.1%)
Vomiting	9/38 (23.7%)
General disorders
Edema limbs	3/38 (7.9%)
Fatigue	21/38 (55.3%)
Fever	2/38 (5.3%)
Infections and infestations
Infections and infestations - Other, specify	11/38 (28.9%)
Wound infection	1/38 (2.6%)
Investigations
Alanine aminotransferase increased	3/38 (7.9%)
Alkaline phosphatase increased	1/38 (2.6%)
Aspartate aminotransferase increased	1/38 (2.6%)
Blood bilirubin increased	2/38 (5.3%)
Investigations - Other, specify	1/38 (2.6%)
Platelet count decreased	6/38 (15.8%)
Weight loss	7/38 (18.4%)
Metabolism and nutrition disorders
Anorexia	12/38 (31.6%)
Hyperglycemia	7/38 (18.4%)
Hypoalbuminemia	1/38 (2.6%)
Hypocalcemia	1/38 (2.6%)
Hypoglycemia	1/38 (2.6%)
Hypokalemia	1/38 (2.6%)
Hyponatremia	4/38 (10.5%)
Nervous system disorders
Ataxia	11/38 (28.9%)
Cognitive disturbance	16/38 (42.1%)
Depressed level of consciousness	15/38 (39.5%)
Dizziness	13/38 (34.2%)
Dysphasia	4/38 (10.5%)
Headache	19/38 (50%)
Memory impairment	15/38 (39.5%)
Peripheral motor neuropathy	15/38 (39.5%)
Peripheral sensory neuropathy	8/38 (21.1%)
Seizure	3/38 (7.9%)
Tremor	5/38 (13.2%)
Psychiatric disorders
Confusion	14/38 (36.8%)
Depression	18/38 (47.4%)
Insomnia	17/38 (44.7%)
Renal and urinary disorders
Urinary incontinence	6/38 (15.8%)
Reproductive system and breast disorders
Reproductive system and breast disorders - Other, specify	9/38 (23.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	9/38 (23.7%)
Skin and subcutaneous tissue disorders
Rash acneiform	6/38 (15.8%)
Rash maculo-papular	9/38 (23.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Institution will provide Eisai with a copy of any manuscript, paper, or poster connected with the study at least 30 days prior to submission to journal/presentation in order for Eisai to review for Eisai's Confidential Information (CI). Should Eisai notify Institution with such 30 day period that materials contain CI, Institution agrees to delay submission/publication/presentation for an additional 60 days to allow Eisai to seek patent or other protection.