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Intravenous Palonosetron With Radiotherapy and Concomitant Temozolomide

Phase 2
Completed
Conditions
Malignant Glioma
Interventions
Registration Number
NCT00900757
Lead Sponsor
Duke University
Brief Summary

1. Purpose and objective:

1. 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).

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

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

2. 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.

3. 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
57
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.
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
PalonosetronPalonosetron (PALO)Single Arm trial of Palonosetron for the prevention of RINV in primary malignant glioma patients receiving radiation therapy (RT) and concomitant temozolomide (TMZ)
Primary Outcome Measures
NameTimeMethod
Safety and Tolerability of Palonosetron as Determined by the Number of Participants Who Experience Unacceptable Toxicity6 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
NameTimeMethod
Change in the Functional Living Index - Emesis (FLIE) Score From Baseline to Each Week of Radiation (XRT) and Temozolomide (TMZ) Treatment6 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.

Complete Response6 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).

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.

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.

Trial Locations

Locations (1)

The Preston Robert Tisch Brain Tumor Center at Duke

🇺🇸

Durham, North Carolina, United States

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