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

This study has been terminated.
(Study was halted early after 63 subjects were enrolled due to slow accrual.)
Sponsor:
Collaborators:
Eisai Inc.
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00636805
First received: February 27, 2008
Last updated: March 4, 2014
Last verified: March 2014
  Purpose
  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.

Condition Intervention Phase
Brain Cancer
Drug: Palonosetron (Aloxi) and Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Acute CINV (Chemotherapy Induced Nausea and Vomiting) CR (Complete Response) Rate [ Time Frame: first 24 hours of the first week of chemotherapy ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate by Corticosteroid Use at Baseline [ Time Frame: Day 1 of the first week of chemotherapy ] [ Designated as safety issue: No ]
    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.

  • Acute Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate by Anticoagulant Use at Baseline [ Time Frame: Day 1 of the first week of chemotherapy ] [ Designated as safety issue: No ]
    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.

  • Delayed Chemotherapy-Induced Nausea and Vomiting (CINV) Complete Response (CR) Rate [ Time Frame: Days 2-5 of the first week of chemotherapy ] [ Designated as safety issue: No ]
    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

  • Percentage of Patients With ≥ Grade 3, Treatment-related Toxicities [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Percentage of patients with ≥ grade 3, treatment-related toxicities using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

  • 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 [ Time Frame: Baseline through day 5 of the first week of chemotherapy ] [ Designated as safety issue: No ]
    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.

  • 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) [ Time Frame: Baseline through day 5 of the first week of chemotherapy ] [ Designated as safety issue: No ]
    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.


Enrollment: 63
Study Start Date: May 2008
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Aloxi

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00636805

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Eisai Inc.
Investigators
Principal Investigator: Mary Lou Affronti, RN, MSN, ANP Duke University
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00636805     History of Changes
Other Study ID Numbers: Pro00002273, P50NS020023
Study First Received: February 27, 2008
Results First Received: January 9, 2014
Last Updated: March 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Aloxi
Brain Neoplasm, Primary
Brain Neoplasms, Malignant

Additional relevant MeSH terms:
Brain Neoplasms
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms
BB 1101
Bevacizumab
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Irinotecan
Palonosetron
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Growth Inhibitors
Growth Substances
Hormones

ClinicalTrials.gov processed this record on October 21, 2014