Clinical trial NCT01268566: A Study of MEDI-575 in Subjects With Recurrent Glioblastoma Multiforme
Official title: A Phase 2 Study of MEDI-575 in Adult Subjects With Recurrent Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Glioblastoma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2010-12-31
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this Phase II study is to evaluate the progression-free survival at 6 months in adult subjects with a first recurrence of Glioblastoma Multiforme who are treated with MEDI-575.

Detailed description: This is a Phase 2, multicenter, open-label, single-arm study to evaluate the antitumor activity, safety, and pharmacology of MEDI-575 in adult subjects with first recurrence of GBM.

Approximately 55 subjects will be enrolled to determine the preliminary efficacy profile of MEDI-575 in the treatment of subjects with first recurrence of GBM. Subjects will receive MEDI-575 as a 60-minute IV infusion on Day 1 every 21 days until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, or other reasons for subject withdrawal.

The primary assessment of antitumor activity is PFS-6; tumor response and progression will be determined using Updated Response Assessment Criteria of High Grade Gliomas- Neuro-Oncology Working Group v.1. Approximately 15 investigational sites in the United States will participate in this study. All subjects will be followed every 3 months for the duration of the trial (defined as 9 months from the date the last subject is entered into the trial or when the sponsor stops the study.

Eligibility criteria: Inclusion Criteria:

* Written informed consent and HIPAA authorization (applies to covered entities in the USA only) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
* Age ≥18 years old at the time of screening
* Histologically confirmed diagnosis of World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma)
* Previous first line treatment with radiotherapy and temozolomide (treatment prior to radiation and temozolomide permitted, \[ie, Gliadel\])
* Documented first recurrence of GBM by diagnostic biopsy or by contrast-enhanced magnetic resonance imaging (MRI) as per Updated Response Assessment Criteria of High Grade Gliomas- Neuro-Oncology Working Group (Wen et al, 2010)
* Life expectancy ≥ 12 weeks
* Adequate hematologic and organ function
* Negative serum pregnancy test (women only)
* Two methods of birth control for female participants of child-bearing potential or male participants with their female partners of child-bearing potential

Exclusion Criteria:

* Treatment with any chemotherapy, radiotherapy, immunotherapy, biologic, hormonal therapy or investigational agent 30 days prior to study entry
* Concurrent enrollment in another clinical study involving an investigational agent
* Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals
* Previous mAb treatment specifically directed against PDGF or PDGF receptors
* Previous bevacizumab or other VEGF and anti-angiogenic treatment
* More than 1 recurrence of GBM
* Any surgery (not including minor diagnostic procedures) within 2 weeks prior to baseline disease assessments; or not fully recovered from any side effects of previous procedures
* History of serious allergy or reaction to any component of the MEDI-575 formulation
* New York Heart Association ≥ Grade 2 congestive heart failure within 6 months prior to study entry
* Uncontrolled or significant cardiovascular disease
* History of other invasive malignancy within 5 years prior to study entry except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured
* History of active human immunodeficiency virus or active hepatitis B or C viral infection will be excluded to eliminate the risk of increased AEs due to immune compromise.
* Systemic immunosuppressive therapy.
* Subjects taking corticosteroids must be on a stable dose for 7 days prior to initiation of treatment with MEDI-575 16) Presence of extracranial metastatic or leptomeningeal disease

Primary outcomes:
measure: Progression-free Survival Rate at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Percentage of Participants With Best Overall Response
timeFrame: Study entry through the end of the study, up to 21 months
measure: Percentage of Participants With Objective Response
timeFrame: Study entry through the end of the study, up to 21 months
measure: Time to Response
measure: Duration of Response
measure: Time to Progression
timeFrame: Study entry until the first documented disease progression, up to 16 months
measure: Progression-free Survival Rate at 3 Months and 9 Months
timeFrame: 3 months and 9 months
measure: Progression-free Survival
timeFrame: 9 months
measure: Overall Survival
timeFrame: Study entry to death, up to 16 months
measure: Percentage of Participants With Expression of PDGFR Alpha in the Tumor Samples
timeFrame: Screening (Day-28 to Day -1)
measure: Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events
timeFrame: Baseline to last record on study, up to 21 months
measure: Number of Participants With Worst ECOG Performance Status On-study and Last Record On-study
timeFrame: Baseline to last record on study, up to 21 months
measure: Treatment-emergent Adverse Events Related to Laboratory Parameters
timeFrame: Baseline to last record on study, up to 21 months
measure: Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations
timeFrame: Baseline to last record on study, up to 21 months
measure: Treatment-emergent Adverse Events Related to Vital Sign Parameters
timeFrame: Baseline to last record on study, up to 21 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Stanford
country: United States
facility: Research Site
state: California
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: New York
country: United States
facility: Research Site
state: New York
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site
state: Washington
Study officials:
References: