Aloxi for Prevention of Chemotherapy Induced Nausea and Vomiting in Malignant Glioma Patients Receiving Irinotecan With Bevacizumab
Condition: Brain Cancer
MeSH terms: Glioma; Brain Neoplasms; Vomiting
Intervention: Palonosetron (Aloxi) and Dexamethasone
Intervention description: 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.
Intervention MeSH terms: Dexamethasone; Palonosetron
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Aloxi; Brain Neoplasm, Primary; Brain Neoplasms, Malignant

Summary:

      1. 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.

        2. 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.
    

Eligibility criteria:

        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.