A Study to Evaluate the Safety, Tolerability and Immunogenicity of EGFR(V)-EDV-Dox in Subjects With Recurrent Glioblastoma Multiforme (GBM) (CerebralEDV)
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of EGFR (Vectibix® Sequence)-Targeted EnGeneIC Dream Vectors Containing Doxorubicin (EGFR(V)-EDV-Dox) in Subjects With Recurrent Glioblastoma Multiforme (GBM)|
- Safety outcome measures: Adverse Events (AE's) graded according to CTCAE V.4.3, physical/neurologic examination, Karnofsky Performance Status (KPS), vital signs, echocardiogram, ECG, hematology, serum chemistry & urinalysis. [ Time Frame: Safety measures will be conducted from Study Day 1 as per study schedule to safety follow-up visit 30 (+5 days) post last dose. ]
- Efficacy outcome measure: Disease response will be measured by Magnetic Resonance Imaging (MRI) using Response Assessment in Neuro-Oncology (RANO). [ Time Frame: Screening, then post cycle (Days 50-56) ]
- Identification of a recommended Phase 2 dose (RP2D) of EGFR(V)-EDV-Dox in subjects with recurrent GBM : Dose limiting toxicity (DLT) evaluable subjects. [ Time Frame: DLT evaluable subjects are those who experience a DLT during the evaluation period, between days 1-28. In subjects with an elevated interleukin-6 (IL-6) the DLT evaluation period is days 1-42 for 5 x 10^9 and days 1-49 for 8 x 10^9. ]
- Overall survival outcome measure. [ Time Frame: The number of days from the date of first administration of EGFR(V)-EDV-Dox to the date of death, regardless of cause up to 60 months. ]
|Actual Study Start Date:||February 2017|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||February 2019 (Final data collection date for primary outcome measure)|
EGFR(V)-EDV-Dox administered via 20 minute intravenous infusion once a week for seven weeks (1 Cycle). Subjects will receive one of two dose levels: 5 x 10^9 or 8 x 10^9. Subjects may receive further cycles of treatment if the tumor remains stable or is responding, and/or they are deriving clinical benefit from the therapy and are tolerating treatment.
EGFR(V)-EDV-Dox using EnGeneIC EDV™ technology is a bacterially derived minicell which packages a toxic payload, Doxorubicin, into a 400 nm particle which targets specific cancer cells using bispecific antibodies (BsAb). BsAb-targeted, payload-packaged EDV nanocells only exit the leaky blood vessels associated with tumors and enter into the tumor microenvironment. The BsAb binds to the tumor cell-surface receptor, where the EDV is taken up, broken down within the cancer cell and releases the Doxorubicin. The residual EDVs that do not make it into the tumor microenvironment, are engulfed by cells of the immune system and since the EDVs are derived from bacteria, they carry potent immuno-stimulating components which appear to bypass the immuno-suppression caused by the tumor.
This is an open-label, Phase 1, dose exploration and preliminary immunogenicity study of single agent EGFR(V)-EDV-Dox in subjects with recurrent glioblastoma (GBM). Eligible subjects enrolled in the study will receive EGFR(V)-EDV-Dox administered weekly for 7 weeks via IV 20 minute infusion, followed by radiological evaluation at week 8 (1 Cycle). Subjects may continue to receive subsequent cycles of EGFR(V)-EDV-Dox unless the subject becomes intolerant to investigational product (IP), withdraw consent or the individual is no longer receiving clinical benefit (factors taken in to consideration will be disease progression radiologically or clinically, and clinical benefits to quality of life). Tumour assessment will be repeated after each 7 week cycle (week 8).
The study will take place in two parts, Part 1 (Dose Exploration) and Part 2 (Dose Expansion).
Part 1 - Dose Exploration will assess the safety and tolerability of multiple doses of drug at two dose levels (5 x 10^9 and 8 x 10^9) and will enroll prior to Part 2. Three subjects will be recruited per dose level. Enrollment will begin with the 5 x 10^9 dose level, and the decision to enroll to the 8 x 10^9 dose level will follow a comprehensive safety evaluation and a standard 3 + 3 dose escalation study design.
Part 2 - Dose Expansion will be conducted pending safety results of Part 1 to provide guidance regarding the recommended phase 2 dose (RP2D). Subjects will be treated and assessed as outlined in Part 1 above. If 0 out of 3 subjects, or 1 out of 6 subjects, experience dose limiting toxicities (DLTs) at the 5 x 10^9 dose level in Part 1, additional subjects to a total of 10 will be recruited to this dose level in Part 2. Similarly, if 0 out of 3 subjects, or 1 out of 6 subjects, experience DLTs at the 8 x 10^9 dose level in Part 1, additional subjects to a total of 10 will be recruited to this dose level in Part 2. If both dose levels are tolerated, a total of 10 subjects per dose level will be enrolled.
A safety follow-up visit must be performed 30 (+5) days after the last dose of drug for all subjects.All subjects who discontinue investigational product and who have not withdrawn full consent to participate in the study will continue in the long term follow-up phase. Long term follow-up will continue approximately every 1 month for 12 months, from the 30 (+5) day follow-up visit, then approximately every 2-3 months for the extent of subject survival.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02766699
|Contact: Kelly Szajna, RN BSNemail@example.com|
|Contact: Jessica Wollett, MAfirstname.lastname@example.org|
|United States, Maryland|
|John Hopkins Hospital||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Gary Gallia, MD PhD 410-614-0585 email@example.com|
|Contact: Kelly Szajna, RN BS 4105024081 firstname.lastname@example.org|
|Principal Investigator: Gary L Gallia, MD PhD|
|Principal Investigator: Stuart A Grossman, MD|
|Study Director:||Jennifer MacDiarmid, Ph.D||Engeneic Pty Limited|
|Study Director:||Himanshu Brahmbhatt, Ph. D||Engeneic Pty Limited|
|Principal Investigator:||Gary L Gallia, M.D., Ph.D||Johns Hopkins University|
|Principal Investigator:||Stuart A Grossman, M.D.||Johns Hopkins University|