Bevacizumab Plus Irinotecan Plus Carboplatin for Recurrent Malignant Glioma (MG)

NCT00953121 | Completed Phase 2 Results

• 1 other identifier: Pro00016712
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether Bevacizumab, CPT-11 and Carboplatin in combination are effective in the treatment of recurrent malignant glioma.

Conditions

Malignant Glioma

Keywords

irinotecan; carboplatin; bevacizumab; Avastin

Outcome Measures

Primary Outcomes (1)

• 6 Month Progression-free Survival

  Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Response Assessment in Neuro-Oncology (RANO) criteria, or to death due to any cause. Progression is defined as greater than or equal to a 25% increase in the product of the largest perpendicular diameters of any enhancing lesion or any new enhancing tumor on MRI scans. Patients may also be classified as progressive disease with significant neurologic decline felt to be due to underlying tumor and not attributable to co-morbid event or concurrent medication regardless of MRI findings.

  6 months

Secondary Outcomes (4)

• Objective Response Rate

  34 months

• Median Progression Free Survival (PFS)

  40 months

• Median Overall Survival (OS)

  40 months

• Safety of Bevacizumab (Avastin) in Combination With Irinotecan and Carboplatin

  34 months

Study Arms (3)

Cohort A-Grade IV No Failure

EXPERIMENTAL

Recurrent GBM patients who have not previously failed bevacizumab, irinotecan, or carboplatin

Drug: bevacizumab and CPT-11 and Carboplatin

Cohort B-Grade III No Failure

EXPERIMENTAL

Recurrent Grade 3 malignant glioma patients who have not previously failed either bevacizumab, irinotecan or carboplatin

Drug: bevacizumab and CPT-11 and Carboplatin

Cohort C-Failed Prior Therapy

EXPERIMENTAL

Recurrent Grade IV GBM patients who have failed prior bevacizumab therapy, but not prior CPT-11 or carboplatin therapies

Drug: bevacizumab and CPT-11 and Carboplatin

Interventions

bevacizumab and CPT-11 and Carboplatin DRUG

Bevacizumab will be administered at 10mg/kg with irinotecan every other week. The dose of irinotecan will be 125 mg/m2 for patients not on CYP3A-inducing anti=epileptics (EIAEDs) and 340 mg/m2 for patients on EIAEDs. All patients will also receive carboplatin on day 1 of each 28-day treatment cycle. Carboplatin will be dosed to achieve an AUC of 4.

Also known as: bevacizumab, Avastin, Irinotecan, CPT-11, Carboplatin, Paraplatin, Camptosar

Cohort A-Grade IV No Failure; Cohort B-Grade III No Failure; Cohort C-Failed Prior Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohorts A and B only
• No prior failure or grade ≥ 3 toxicity to bevacizumab, irinotecan or carboplatin.
• Cohort C only
• Failure on prior bevacizumab therapy
• No prior failure or grade ≥ 3 toxicity to either irinotecan or carboplatin.
• All Cohorts
• Age \* 18 years
• Karnofsky Performance Status (KPS) ≥ 70%
• No more than 3 prior episodes of disease progression
• An interval of at least 4 weeks between prior surgical resection or one week from stereotactic biopsy
• An interval of at least 12 weeks from the end of prior radiotherapy unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there are progressive changes on MRI on at least two consecutive MRI scans at least four weeks apart, or there is biopsy-proven tumor progression
• An interval of at least 4 weeks from prior chemotherapy (6 weeks for nitrosoureas) or investigational agent unless the patient has recovered from all anticipated toxicities associated with that therapy
• Hematocrit ≥ 29%, absolute neutrophil count (ANC) ≥ 1,000 cells/\*l, platelets ≥ 100,000 cells/\*l
• Serum creatinine ≤ 1.5 times upper limit of normal, serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 times upper limit of normal and bilirubin ≤ 2.0 times upper limit of normal
• International Normalized Ratio (INR) \< 1.5 or prothrombin time/partial thromboplastin time (PT/PTT) within 1.5 time upper limit of normal (ULN).

You may not qualify if:

• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
• Active infection requiring intravenous antibiotics
• Requires therapeutic anti-coagulation with warfarin
• Subjects meeting any of the following criteria are ineligible for study entry:
• Inability to comply with study and/or follow-up procedures
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
• Severe hepatic insufficiency (ongoing grade 3 or greater hepatic adverse events) or known active chronic hepatitis
• Homozygosity for the \*28 uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) allele.
• Inadequately controlled hypertension (defined as systolic blood pressure \> 150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to study enrollment
• History of stroke or transient ischemic attack within 6 months prior to study enrollment
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
• Symptomatic peripheral vascular disease

Sponsors & Collaborators

• Annick Desjardins: lead

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Reardon DA, Desjardins A, Peters KB, Gururangan S, Sampson JH, McLendon RE, Herndon JE 2nd, Bulusu A, Threatt S, Friedman AH, Vredenburgh JJ, Friedman HS. Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naive, recurrent glioblastoma. J Neurooncol. 2012 Mar;107(1):155-64. doi: 10.1007/s11060-011-0722-2. Epub 2011 Oct 11.

  PMID: 21986722 DERIVED

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioma

Interventions

Bevacizumab; Irinotecan; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Dr. Annick Desjardins
• Organization: Preston Robert Tisch Brain Tumor Center at Duke University Medical Center

annick.desjardins@duke.edu

919-684-1691

Study Officials

• Annick Desjardins, MD, FRCPC

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assist Professor of Medicine-Neurology

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 6, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: January 1, 2013
• Last Updated: September 16, 2013
• Results First Posted: September 4, 2013

Record last verified: 2013-09

Locations

US (1)