Aloxi for Prevention of Chemotherapy Induced Nausea and Vomiting in Malignant Glioma Patients Receiving Irinotecan With Bevacizumab

Study Overview
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Brief Summary
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Primary Objective: To determine the efficacy and tolerability of palonosetron and dexamethasone in preventing acute CINV in brain tumor patients during the first 24 hours of receiving Irinotecan /Bevacizumab regimens. Secondary Objective To determine the safety and tolerability of palonosetron in brain tumor patients. To determine the effects of glucocorticoid and anticonvulsants on the efficacy of palonosetron. To determine the efficacy of palonosetron and dexamethasone in preventing delayed CINV in brain tumor patients during days 2-5. To determine if patients receiving palonosetron have less fatigue than baseline.

Detailed Description
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Before the patients receive the palonosetron, a physical exam and blood tests are performed to determine eligibility. If eligible and willing, subjects are given Palonosetron intravenously. Subjects are given the Palonosetron and Dexamethasone 30 minutes before the first dose of Irinotecan and Bevacizumab chemotherapy. The total expected duration of participation is 57 days. Subjects are also asked to complete 4 questionnaires about nausea and vomiting, as well as daily functioning and fatigue. Subjects are asked to complete these questionnaires before starting chemotherapy, the day of starting chemotherapy and for the next 4 days after receiving chemotherapy, for a total of 6 times. Subjects are asked to complete this set of questionnaires each of the 3 times that they receive chemotherapy during the 6-week treatment cycle. The other treatments subjects would normally receive for their brain tumor and their routine care are not affected by the study.

Official Title
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A Phase II Single Arm Trial of Palonosetron (PALO) for the Prevention of Acute and Delayed Chemotherapy Induced Nausea and Vomiting (CINV) in Malignant Glioma (MG) Patients Receiving Irinotecan in Combination With Bevacizumab

Conditions
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Brain Cancer

Intervention / Treatment
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* Drug: Palonosetron (Aloxi) and Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to be included in the study, patients must meet all of the following criteria: Patients must have histologically confirmed diagnosis of primary malignant glioma (glioblastoma multiforme, gliosarcoma or anaplastic astrocytoma, or anaplastic oligodendroglioma) who are either chemotherapy naïve or non-naïve and scheduled to receive Irinotecan/Bevacizumab chemotherapy. Patients with recurrent disease whose diagnostic pathology confirmed malignant glioma (glioblastoma multiforme, gliosarcoma or anaplastic astrocytoma, or anaplastic oligodendroglioma) will not need re-biopsy. Age > or = 18 years. Patient is scheduled to receive Irinotecan/Bevacizumab chemotherapy every 2 weeks for one complete 6-week cycle. An interval of at least 6 weeks between prior surgical resection and study enrollment. An interval of at least 4 weeks between prior radiotherapy and enrollment on this protocol unless there is unequivocal evidence of tumor progression after radiotherapy or chemotherapy. The lab values following the prior chemotherapy must return within normal limits prior to study enrollment. Karnofsky > 60%. Hematocrit > 29%, absolute neutrophil count (ANC) > 1,500 cells/*l, platelets > 125,000 cells/*l. Serum creatinine < 1.5 mg/dl, serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin < 1.5 times upper limit of normal. Patients on corticosteroids must be 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 consent form approved by the Institutional Review Board prior to patient entry. No evidence of hemorrhage on the baseline MRI or CT scan. If sexually active, patients will take contraceptive measures for the duration of the treatments. Exclusion Criteria: Patients are excluded from this study if they meet any of the following criteria: Inability or unwillingness to understand or cooperate with study procedures. Received any intravenous drug with potential anti-emetic effect within 24 hours prior to the start of study-designated chemotherapeutic agent or be scheduled to receive any drug of this type (with the exception of administration of the palonosetron/dexamethasone infusion solution) at any time during the trial, including the following: 5 HT3 receptor antagonists; Dopamine receptor antagonists (metoclopramide); Phenothiazine anti-emetics (prochlorperazine, thiethylperazine and perphenazine); Diphenhydramine, scopolamine, chlorpheniramine maleate, trimethobenzamide. Diphenhydramine will be allowed if given for prophylactic treatment of hypersensitivity reactions associated with the administration of taxanes; Haloperidol, droperidol, tetrahydrocannabinol, or nabilone; and Any systemic corticosteroid (hydrocortisone, methylprednisolone, prednisone). Topical or inhaled preparations are allowed; Previous participation in any clinical trial involving palonosetron (RS-25259 of Syntex). Any vomiting, retching or NCI Common Toxicity Criteria version 3.0 grade 2-4 nausea (see Appendix 8.6) in the 24 hours preceding chemotherapy. Ongoing vomiting from any organic etiology. Will receive radiotherapy of upper abdomen or cranium within one week prior to or during the study. Received palonosetron within 14 days prior to study enrollment (AloxiTM). Evidence of central nervous system (CNS) hemorrhage on baseline MRI on CT scan. Co -medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids. Prophylactic medication for the prevention of nausea and vomiting 24 hours prior to the start of chemotherapy through 120 hours after the initiation of chemotherapy on Study Day 1 (Study Day 6) is prohibited, with the exception of the study drug. Corticosteroids will be allowed for treatment of cerebral swelling. Diphenhydramine will be allowed only if given for prophylactic treatment of hypersensitivity reactions associated with the administration of taxanes, as per the package insert for these agents. Rescue medication for treatment of nausea and vomiting is permitted after chemotherapy at the discretion of the investigator. The agent, dose, and time of administration will be recorded in the patient diary.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Patient receives IV Aloxi | Drug: Palonosetron (Aloxi) and Dexamethasone<br>* single i.v. , dose of palonosetron 0.25 mg, and 10mg dexamethasone infused over 15 min, administered 30 min before the first dose Irinotecan and Bevacizumab chemotherapy.<br>* Other names: Aloxi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute CINV (Chemotherapy Induced Nausea and Vomiting) CR (Complete Response) Rate | Acute Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment. | first 24 hours of the first week of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate by Corticosteroid Use at Baseline | Acute Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment. | Day 1 of the first week of chemotherapy | 
| Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate by Anticoagulant Use at Baseline | Acute Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment. | Day 1 of the first week of chemotherapy | 
| Delayed Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate | Delayed Chemotherapy-Induced Nausea and Vomiting (CINV) complete response (CR) rate is defined as the percentage of patients who do not have an emetic episode or use antiemetic rescue medication during days 2 through 5 of chemotherapy treatment during the first cycle of treatment | Days 2-5 of the first week of chemotherapy | 
| Percentage of Patients With ≥ Grade 3, Treatment-related Toxicities | Percentage of patients with ≥ grade 3, treatment-related toxicities using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. | 6 weeks | 
| Overall Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline to Day 5 of the First Week of Chemotherapy | Overall mean change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to day 5 of the first week of chemotherapy. The FACIT-Fatigue is a 13-item validated questionnaire assessing the impact of fatigue on an individual's quality of life. The raw score range is 0-52 with higher scores indicating better quality of life. The mean change from baseline to day 5 was calculated by subtracting the baseline score from mean of the day 1-5 scores, thus a negative mean change represents worsening in quality of life due to fatigue. | Baseline through day 5 of the first week of chemotherapy | 
| Overall Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score From Baseline to Day 5 of the First Week of Chemotherapy by Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) | Overall mean change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score from baseline to day 5 of the first week of chemotherapy. The FACIT-Fatigue is a 13-item validated questionnaire assessing the impact of fatigue on an individual's quality of life. The raw score range is 0-52 with higher scores indicating better quality of life. The mean change from baseline to day 5 was calculated by subtracting the baseline score from the mean of the day 1-5 scores, thus a negative mean change represents worsening in quality of life due to fatigue. Acute CINV complete response (CR) is defined as not having an emetic episode or any use of antiemetic rescue medication during the first 24 hours following chemotherapy of the first cycle of treatment. | Baseline through day 5 of the first week of chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aloxi, Brain Neoplasm, Primary, Brain Neoplasms, Malignant