Clinical trial NCT02546102: Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma
Official title: A Phase 3 Randomized Double-blind, Controlled Study of ICT-107 With Maintenance Temozolomide (TMZ) in Newly Diagnosed Glioblastoma Following Resection and Concomitant TMZ Chemoradiotherapy
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: Glioblastoma Multiforme
Lead sponsor: Precision Life Sciences Group
Sponsor class: INDUSTRY
Collaborators: name: Medelis Inc.
First posted: 2015-09-10
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: ICT-107 consists of dendritic cells, prepared from autologous mononuclear cells that are pulsed with six synthetic peptides that were derived from tumor associated antigens (TAA) present on glioblastoma tumor cells. This is a Phase 3 study to evaluate ICT-107 in patients with newly diagnosed glioblastoma. Subjects will be randomized to receive standard of care chemoradiation (temozolomide (TMZ) with either ICT-107 or a blinded control. Reinfusion with the pulsed dendritic cells should stimulate cytotoxic T cells to specifically target glioblastoma tumour cells.

Detailed description: This is a double blind Phase III study where eligible subjects are randomized into two treatment arms following the SOC primary treatment with chemoradiation: Arm 1 will receive ICT-107 in combination with the standard of care, temozolomide (TMZ), Arm 2 will receive TMZ with a blinded control. A 1:1 randomization will be employed, where ARM 1 will receive ICT-107 and Arm 2 will receive placebo control. All subjects must be HLA-A2+. All subjects must have glioblastoma tissue that has tumor assessment for MGMT methylation status prior to randomization (for stratification). Subjects will have had tumor resection and magnetic resonance imaging (MRI) prior to enrollment into the study. After signing of written informed consent and any required privacy compliance forms and screening, enrolled subjects will undergo large volume apheresis at the study site for collection of PBMCs. Apheresis product will be sent to the manufacturing site where both active therapy (ICT-107) and control will be prepared for each subject prior to randomization The study period consists of 4 time periods; a 6-week Post-Surgery Standard of Care Treatment Phase where subjects receive radiotherapy and TMZ; TMZ and radiation to be initiated no more than 8 weeks after surgical resection of glioblastoma; a Rest Period of no more than 14 days where subjects are reassessed for eligibility, and then randomized; a 4 week Induction Phase where study therapy (ICT-107 or Control) is given weekly; followed by a Maintenance Phase where study therapy is given monthly for 11 months, and then every 6 months until either progression, withdrawal from the study, death, or the supply of autologous study therapy is exhausted. Randomized subjects will receive 4 weekly administrations of subject-specific study therapy (ICT-107 or Control) during the Induction Phase. No TMZ will be given during the 4 week Induction Phase. Each study therapy injection will be delivered intradermally (axilla).

The Maintenance Phase will consist of administration of subject-specific study therapy monthly for 11 months after the Induction Phase (for a total of 15 injections over 12 months during the Induction and Maintenance Phases), and then every 6 mos. thereafter until depletion or confirmation of progressive disease (PD). During the Maintenance Phase (where ICT-107 or control are given monthly), the administration of TMZ and subject specific study therapy or control will be separated in time by approximately 2 weeks (see Section 9.1.4). Pre-treatment, treatment and assessment schedules will be the same for all subjects.

Eligibility criteria: Inclusion Criteria:

1. Subjects must understand and sign the study specific informed consent
2. Subjects must be in primary remission
3. Subjects should have \< 1 cm3 disease by MRI within the previous 4 weeks (by central read)
4. Subjects must be HLA-A2 positive by central lab
5. Subjects must have adequate renal, hepatic and bone marrow function based on screening laboratory assessments. Baseline hematologic studies and chemistry and coagulation profiles must meet the following criteria:

   1. Hemoglobin (Hgb) \> 8 g/dL
   2. Absolute Neutrophil Count (ANC) \> 1000/mm3
   3. Platelet count \> 100,000/mm3
   4. Blood Urea Nitrogen (BUN) \< 30 mg/dL
   5. Creatinine \< 2 mg/dL
   6. Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) \< 2 x upper limit of normal (ULN)
   7. Prothrombin Time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6x unless therapeutically warranted
6. Subjects must use effective contraceptive methods during the study and for three months following the last dose of study product, if of reproductive age and still retain fertility potential.
7. Subjects must have at least one positive DTH skin response (more than 5 mm) to test item challenge prior to randomization.

Exclusion Criteria:

1. Subjects receiving investigational study drug for any indication or immunological-based treatment for any reason (Filgrastim may be used for prevention of severe neutropenia).
2. Subjects with glioblastoma mutated IDH by Immunohistochemistry (IHC)
3. Subjects with concurrent conditions that would jeopardize the safety of the subject or compliance with the protocol.
4. Subjects with a history of chronic or acute hepatitis C or B infection.
5. Subjects require or are likely to require more than a 2-week course of corticosteroids for intercurrent illness. Subjects must have completed the course of corticosteroids at the time of apheresis to meet eligibility.
6. Subjects have any acute infection that requires specific therapy. Acute therapy must have been completed within seven days prior to study enrollment.
7. Subjects with active other malignancy diagnosed in the past 3 years (excepting in situ tumors)
8. Subjects known to be pregnant or nursing.

Primary outcomes:
measure: Overall survival
timeFrame: 46 months
Secondary outcomes:
measure: Overall survival in patients with unmethylated MGMT tumors
timeFrame: 46 months
measure: Overall survival in patients with methylated MGMT (O6-methylguanine-DNA methyltransferase) tumors
timeFrame: 46 months
measure: Progression-free survival
timeFrame: 46 months
measure: Type and frequency of treatment emergent adverse events
timeFrame: 46 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Dignity Health - St. Joseph's Hospital and Medical Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine Chao Family Cancer Center
state: California
city: Redwood City
country: United States
facility: Kaiser Permanente
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Fairfield
country: United States
facility: Associated Neurologists of Southern Connecticut
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Hospital
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Health Services
state: Delaware
city: Boca Raton
country: United States
facility: Delray Medical Center
state: Florida
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital Lynn Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Harvard Medical School Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Minneapolis
country: United States
facility: John Nasseff Neuroscience Institute
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro-Minnesota Community Oncology Research Consortium
state: Minnesota
city: Edison
country: United States
facility: JFK New Jersey Neuroscience Institute
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Lake Success
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weil Cornell Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Hershey
country: United States
facility: Penn State College of Medicine Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Cancer Pavilion
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Medical Cancer Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Baylor Health Charles Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center Memorial Hermann Hospital
state: Texas
city: San Antonio
country: United States
facility: CTRC at UTHSCSA
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: Ivy Center for Advanced Brain Tumor Treatment Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Innsbruck
country: Austria
facility: Medical University Innsbruck, Dept. of Neurology
city: Linz
country: Austria
facility: Kepler Universitätsklinikum, Neuromed Campus
city: Salzburg
country: Austria
facility: University Clinic for Neurology
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute & Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS Service de Neurochirurgie
state: Quebec
Study officials:
References:
citation: Phuphanich S, Wheeler CJ, Rudnick JD, Mazer M, Wang H, Nuno MA, Richardson JE, Fan X, Ji J, Chu RM, Bender JG, Hawkins ES, Patil CG, Black KL, Yu JS. Phase I trial of a multi-epitope-pulsed dendritic cell vaccine for patients with newly diagnosed glioblastoma. Cancer Immunol Immunother. 2013 Jan;62(1):125-35. doi: 10.1007/s00262-012-1319-0. Epub 2012 Jul 31.