A Study in Subjects With Recurrent Malignant Glioma

NCT01137604 | Completed Phase 2 Results FDA Drug

• 1 other identifier: E7080-G000-203
• Study Type: interventional
• Target: 151
• Locations: 2 countries
• Sites: 5

Brief Summary

An open-label phase 2, multicenter study in participants with recurrent malignant glioma.

Conditions

Glioma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Rate at Month 6

  PFS at Month 6 was defined as the percentage of participants who remained alive and progression-free at Month 6, based on investigator's assessment. Progression was defined using Response Assessment in Neuro-Oncology (RANO) criteria, as a greater than 25% increase in enhancing lesions despite stable or increasing steroid dose, an increase (significant) in non-enhancing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) lesions that are not attributable to other non-tumor causes, and any new lesions. PFS rate at Month 6 was estimated from Kaplan-Meier (K-M) product-limit estimate of PFS.

  At Month 6 from randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3)

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (i.e., 2.4 years)

• Progression Free Survival

  From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

• Overall Survival (OS)

  From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until death due to any cause or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

• Disease Control Rate (DCR)

  From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

• Clinical Benefit Rate (CBR)

  From date of randomization (Cohort 1) or first day of treatment (Cohorts 2 and 3) until disease progression, development of unacceptable toxicity, withdrawal of consent or up to data cutoff date of 19 March 2013 (ie, 2.4 years)

Study Arms (3)

Cohort 1

EXPERIMENTAL

Cohort 1 assessed participants with recurrent Grade 4 malignant glioma (ie, glioblastoma \[GBM\]) who were bevacizumab-naive. Participants were planned to be accrued in Cohort 1 and randomized in a 1:1 ratio to receive lenvatinib (experimental) or bevacizumab (active comparator). Cohort 1 - Bevacizumab Cohort 1 - Lenvatinib

Drug: Lenvatinib; Drug: Bevacizumab

Cohort 2

EXPERIMENTAL

Cohort 2 assessed participants with recurrent Grade 3 malignant glioma who were bevacizumab-naive. Participants in Cohort 2 were planned to be treated with lenvatinib.

Drug: Lenvatinib

Cohort 3

EXPERIMENTAL

Cohort 3 assessed participants with recurrent GBM who had disease progression following prior bevacizumab treatment. Participants in Cohort 3 were planned to be treated with lenvatinib.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

24 mg lenvatinib capsules orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.

Also known as: E7080

Cohort 1; Cohort 2; Cohort 3

Bevacizumab DRUG

Bevacizumab 10 mg/kg administered intravenously every 2 weeks in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.

Cohort 1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of Grade 3 or 4 malignant glioma.
• All subjects who have a first or second recurrence following primary management with surgical resection or biopsy, radiotherapy and up to 2 prior systemic treatments with addition of:
• No prior bevacizumab treatment is allowed for Cohort 1 and Cohort 2.
• Subjects must have disease progression following prior bevacizumab treatment for Cohort 3.
• For all cohorts, no prior anti-vascular endothelial growth factor (VEGF/VEGFR) therapy except for bevacizumab as specified above.
• Karnofsky score of 70% or greater.
• Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.
• Adequate renal function, adequate bone marrow function, adequate blood coagulation function and adequate liver function, as defined in protocol.
• No evidence of hemorrhage on the baseline magnetic resonance imaging (MRI) scan other than in those subjects who are stable grade 1.

You may not qualify if:

• Females who are pregnant or breastfeeding.
• Subjects who received enzyme-inducing anti-epileptic agents within 14 days before the first dose of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone, or oxcarbazepine).
• Active infection requiring intravenous antibiotics.
• Therapeutic anti-coagulation with warfarin, aspirin, nonsteroidal anti-inflammatory drugs or clopidogrel (low molecular weight heparin is acceptable).
• Subjects with 24-hour urine protein greater than or equal to 1 gm.
• Prior surgical resection within 4 weeks, or prior stereotactic biopsy within 2 weeks, of Screening Visit.
• Prior radiotherapy within 12 weeks unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there is biopsy-proven unequivocal viable tumor on histopathologic sampling.
• Prior chemotherapy (6 weeks for nitrosoureas), or any investigational agent within 4 weeks unless the subject has recovered from all anticipated toxicities associated with that therapy; prior bevacizumab therapy (Cohorts 1 and 2); for Cohort 3, prior bevacizumab therapy within 3 weeks.
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II ; unstable angina; myocardial infarction or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment.
• Prolongation of QTc interval to greater than 480 msec.
• Active hemoptysis (bright red blood of at least 1/2 teaspoon) within 3 weeks prior to the first dose of study drug.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (5)

Unknown Facility

Tampa, Florida, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Durham, North Carolina, United States

Location

Unknown Facility

Calgary, Canada

Location

Unknown Facility

Toronto, Canada

Location

MeSH Terms

Conditions

Glioma

Interventions

lenvatinib; Bevacizumab

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

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai, Inc.

esi_medinfo@eisai.com

1-888-422-4743

Study Officials

• Eisai Medical Services

  Eisai Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2010
• First Posted: June 4, 2010
• Study Start: November 9, 2010
• Primary Completion: March 19, 2013
• Study Completion: October 28, 2014
• Last Updated: September 29, 2022
• Results First Posted: May 23, 2016

Record last verified: 2016-05

Locations

CA (2); US (3)