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

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

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.

Study Overview

• Status: Terminated
• Conditions: Brain Cancer
• Intervention / Treatment: Drug: Palonosetron (Aloxi) and Dexamethasone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Patient receives IV Aloxi	Drug: Palonosetron (Aloxi) and Dexamethasone; 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.; Other Names: Aloxi

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Eisai Inc.
• Investigators: Principal Investigator: Mary Lou Affronti, RN, MSN, ANP, Duke University

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: February 27, 2008
• First Submitted That Met QC Criteria: March 13, 2008
• First Posted (Estimate): March 14, 2008

Study Record Updates

• Last Update Posted (Estimate): April 1, 2014
• Last Update Submitted That Met QC Criteria: March 4, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Brain Neoplasms, Malignant; Aloxi; Brain Neoplasm, Primary
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Signs and Symptoms, Digestive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Vomiting; Glioma; Brain Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Dexamethasone; Palonosetron
• Other Study ID Numbers: Pro00002273; P50NS020023 (U.S. NIH Grant/Contract)