Aloxi for Prevention of Acute and Delayed Chemotherapy Induced Nausea and Vomiting (CINV) in Malignant Glioma (MG) Patients Receiving Irinotecan With Bevacizumab

Condition(s) targeted: Brain Cancer

Intervention: Palonosetron (Aloxi) and Dexamethasone (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Duke University

Official(s) and/or principal investigator(s):
Lee Jones, PhD, Principal Investigator, Affiliation: Duke University

Overall contact:
Cindy Bohlin, RN, Phone: 919-684-0224, Email: cindy.bohlin@duke.edu

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.

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

Study design: Supportive Care, Open Label, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Response for Chemotherapy Induced nausea and vomiting

Secondary outcome: Tolerability

Detailed description: Before you receive the drug, you will have a physical exam and blood tests to determine you are able to take part. If you choose to participate in this study, you will sign a consent form. You will then get a medication called Palonosetron. Palonosetron will be given into a vein. This will take fifteen minutes. You will be given the Palonosetron and Dexamethasone 30 minutes before your first dose of Irinotecan and Bevacizumab chemotherapy. The total expected duration of your participation is 57 days. You will also be asked to complete 4 questionnaires asking questions about nausea and vomiting, your daily functioning and fatigue. You will be asked to complete these questionnaires before to starting your chemotherapy, the day you start your chemotherapy and for the next 4 days after receiving chemotherapy, for a total of 6 times. You will be asked to complete this set of questionnaires each of the 3 times that you receive chemotherapy during your 6-week treatment cycle.

The other treatments you would normally receive for your brain tumor and your routine care will not be affected by the study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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%, ANC > 1,500 cells/*l, platelets > 125,000 cells/*l.

- Serum creatinine < 1. 5 mg/dl, serum 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 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.

Cindy Bohlin, RN, Phone: 919-684-0224, Email: cindy.bohlin@duke.edu

Duke University Medical Center, Durham, North Carolina 27710, United States

Starting date: May 2008
Ending date: October 2008
Last updated: May 4, 2008