Phase 3 Randomized, Double-blind, Controlled Study of ICT-107 in Glioblastoma

Sponsor

Precision Life Sciences Group (Industry)

Overall Status

Suspended

CT.gov ID

NCT02546102

Collaborator

Novella Clinical (Other)

414

Enrollment

Locations

Arms

Duration (Months)

6.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme	Biological: ICT-107 Biological: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

414 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Dec 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2019

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Arm 1 will receive ICT-107 in combination with the standard of care, temozolomide (TMZ). ICT-107 will be given once a week for 4 weeks in the induction phase. During the maintenance phase, ICT-107 will be given monthly for the 11 months after induction and once every 6 months thereafter until depletion of supply or confirmation of progressive disease (PD). Administration is intradermal in axilla.	Biological: ICT-107 Autologous dendritic cells pulsed with peptides associated with tumor antigens
Placebo Comparator: 2 Arm 2 will receive TMZ with a blinded control. Control will be given once a week for 4 weeks in the induction phase. During the maintenance phase, Control will be given monthly for the 11 months after induction and once every 6 months thereafter until depletion of supply or confirmation of progressive disease (PD). Administration is intradermal in axilla.	Biological: Placebo

Arm

Intervention/Treatment

Experimental: 1

Arm 1 will receive ICT-107 in combination with the standard of care, temozolomide (TMZ). ICT-107 will be given once a week for 4 weeks in the induction phase. During the maintenance phase, ICT-107 will be given monthly for the 11 months after induction and once every 6 months thereafter until depletion of supply or confirmation of progressive disease (PD). Administration is intradermal in axilla.

Biological: ICT-107

Autologous dendritic cells pulsed with peptides associated with tumor antigens

Placebo Comparator: 2

Arm 2 will receive TMZ with a blinded control. Control will be given once a week for 4 weeks in the induction phase. During the maintenance phase, Control will be given monthly for the 11 months after induction and once every 6 months thereafter until depletion of supply or confirmation of progressive disease (PD). Administration is intradermal in axilla.

Biological: Placebo

Outcome Measures

Primary Outcome Measures

Overall survival [46 months]
Overall survival (OS) of subjects treated with ICT-107 and standard of care (radiation (RT) and TMZ) vs. placebo control and standard of care (RT and TMZ)

Secondary Outcome Measures

Overall survival in patients with unmethylated MGMT tumors [46 months]
OS of subjects with unmethylated MGMT (O6-methylguanine-DNA methyltransferase) tumors treated with ICT-107 and standard of care vs. control and standard of care
Overall survival in patients with methylated MGMT (O6-methylguanine-DNA methyltransferase) tumors [46 months]
OS of subjects with methylated MGMT tumors treated with ICT-107 and standard of care vs. control and standard of care.
Progression-free survival [46 months]
Progression-free survival (PFS) of subjects treated with ICT-107 and standard of care vs. control and standard of care
Type and frequency of treatment emergent adverse events [46 months]
Compare the type and frequency of treatment emergent adverse events of ICT-107 vs. control treatment groups

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must understand and sign the study specific informed consent
Subjects must be in primary remission
Subjects should have < 1 cm3 disease by MRI within the previous 4 weeks (by central read)
Subjects must be HLA-A2 positive by central lab
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:
Hemoglobin (Hgb) > 8 g/dL
Absolute Neutrophil Count (ANC) > 1000/mm3
Platelet count > 100,000/mm3
Blood Urea Nitrogen (BUN) < 30 mg/dL
Creatinine < 2 mg/dL
Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) < 2 x upper limit of normal (ULN)
Prothrombin Time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6x unless therapeutically warranted
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.
Subjects must have at least one positive DTH skin response (more than 5 mm) to test item challenge prior to randomization.

Exclusion Criteria:

Subjects receiving investigational study drug for any indication or immunological-based treatment for any reason (Filgrastim may be used for prevention of severe neutropenia).
Subjects with glioblastoma mutated IDH by Immunohistochemistry (IHC)
Subjects with concurrent conditions that would jeopardize the safety of the subject or compliance with the protocol.
Subjects with a history of chronic or acute hepatitis C or B infection.
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.
Subjects have any acute infection that requires specific therapy. Acute therapy must have been completed within seven days prior to study enrollment.
Subjects with active other malignancy diagnosed in the past 3 years (excepting in situ tumors)
Subjects known to be pregnant or nursing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Dignity Health - St. Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
3	City of Hope Cancer Center	Duarte	California	United States	91010
4	UCSD Moores Cancer Center	La Jolla	California	United States	92093
5	Southern California Permanente Medical Group	Los Angeles	California	United States	90027
6	University of Southern California	Los Angeles	California	United States	90033
7	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
8	University of California Irvine Chao Family Cancer Center	Orange	California	United States	92868
9	Kaiser Permanente	Redwood City	California	United States	94063
10	Kaiser Permanente	Sacramento	California	United States	95825
11	John Wayne Cancer Institute	Santa Monica	California	United States	90404
12	Stanford Cancer Institute	Stanford	California	United States	95124
13	University of Colorado Denver	Aurora	Colorado	United States	80045
14	Associated Neurologists of Southern Connecticut	Fairfield	Connecticut	United States	06824
15	Smilow Cancer Hospital	New Haven	Connecticut	United States	06519
16	Christiana Care Health Services	Newark	Delaware	United States	19711
17	Delray Medical Center	Boca Raton	Florida	United States	33484
18	Boca Raton Regional Hospital Lynn Cancer Institute	Boca Raton	Florida	United States	33486
19	Piedmont Hospital	Atlanta	Georgia	United States	30309
20	Georgia Regents University	Augusta	Georgia	United States	30912
21	Northwestern University	Chicago	Illinois	United States	60611
22	NorthShore University Health System	Evanston	Illinois	United States	60201
23	University of Iowa	Iowa City	Iowa	United States	52242
24	University of Kentucky	Lexington	Kentucky	United States	40536
25	Norton Cancer Institute	Louisville	Kentucky	United States	40202
26	Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21287
27	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02114
28	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
29	Harvard Medical School Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
30	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
31	John Nasseff Neuroscience Institute	Minneapolis	Minnesota	United States	55407
32	Metro-Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
33	JFK New Jersey Neuroscience Institute	Edison	New Jersey	United States	08820
34	New Mexico Cancer Care Alliance	Albuquerque	New Mexico	United States	87131
35	North Shore University Hospital	Lake Success	New York	United States	11042
36	Perlmutter Cancer Center	New York	New York	United States	10016
37	Mount Sinai Medical Center	New York	New York	United States	10029
38	Columbia University Medical Center	New York	New York	United States	10032
39	Weil Cornell Medical Center	New York	New York	United States	10065
40	University of Rochester Medical Center	Rochester	New York	United States	14642
41	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
42	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
43	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
44	Penn State College of Medicine Hershey Medical Center	Hershey	Pennsylvania	United States	17033
45	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
46	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
47	University of Pittsburgh Medical Center Cancer Pavilion	Pittsburgh	Pennsylvania	United States	15232
48	University of Tennessee Medical Cancer Institute	Knoxville	Tennessee	United States	37920
49	Texas Oncology	Austin	Texas	United States	78705
50	Baylor Health Charles Sammons Cancer Center	Dallas	Texas	United States	75246
51	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
52	Houston Methodist Hospital	Houston	Texas	United States	77030
53	University of Texas Health Science Center Memorial Hermann Hospital	Houston	Texas	United States	77030
54	CTRC at UTHSCSA	San Antonio	Texas	United States	78229
55	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
56	University of Virginia Health System	Charlottesville	Virginia	United States	22903
57	Ivy Center for Advanced Brain Tumor Treatment Swedish Medical Center	Seattle	Washington	United States	98122
58	University of Washington Medical Center	Seattle	Washington	United States	98195
59	Medical University Innsbruck, Dept. of Neurology	Innsbruck		Austria	6020
60	Kepler Universitätsklinikum, Neuromed Campus	Linz		Austria	4020
61	University Clinic for Neurology	Salzburg		Austria	5020
62	Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
63	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
64	Montreal Neurological Institute & Hospital	Montreal	Quebec	Canada	H3A2B4
65	CHUS Service de Neurochirurgie	Sherbrooke	Quebec	Canada	J1K2R1

Sponsors and Collaborators

Precision Life Sciences Group
Novella Clinical

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Precision Life Sciences Group

ClinicalTrials.gov Identifier:

NCT02546102

Other Study ID Numbers:

ICT-107-301

First Posted:

Sep 10, 2015

Last Update Posted:

Aug 13, 2018

Last Verified:

Aug 1, 2018

Additional relevant MeSH terms:

Glioblastoma

Study Results

No Results Posted as of Aug 13, 2018