The Research on 89Zr-ABT806 PET Imaging in High Grade Glioma

The Research on 89Zr-ABT806 PET Imaging in High Grade Glioma and Its Correlation to EGFRvIII

The epidermal growth factor receptor variant Ⅲ(EGFR vⅢ) is commonly detected in high-grade gliomas, which is also an important epitope in EGFR-targeted therapies and correlated to poor prognosis. However, detection of this mutant usually needs resected tumor samples. For biopsy samples, test results may not represent the EGFR vⅢ status of the whole tumor tissues because of the heterogeneity of tumor. It is also not applicable for patients who are not suitable for surgical procedure due to the tumor location or patients' general conditions. Because of the importance of the epidermal growth factor receptor (EGFR) signal pathway in oncogenesis, maintenance, and progression of high grade glioma, there has been an intense effort to develop noninvasive molecular imaging approach for the selection and monitoring of EGFR-targeted therapies.

Based on investigators' previous study, investigators plan to perform PET scanning on the participants with high grade gliomas after the injection of the second generation of EGFR tracer ,89Zr-ABT806, which can be specifically binded to EGFR vⅢ . After fusing the PET and MRI images, investigators precisely obtain the tissue from the"hot-spot" on the PET image through multimodal-neuronavigation-guided tumor biopsy. EGFRvⅢ status will be detected by molecular methods to analyze the correlation with the 89Zr-ABT806 PET image qualitatively and quantitatively. Investigators' final goal is to detect EGFR vⅢ by noninvasive molecular imaging procedure for the clinical outcome prediction and the selection of EGFR-targeted therapies.

Study Overview

• Status: Unknown
• Conditions: Glioma
• Intervention / Treatment: Diagnostic test: 89Zr-ABT806 PET

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200040
    • Recruiting
    • Huashan Hospital, Fudan University
    • Contact: Liangfu Zhou, Professor; Phone Number: +86-21-52887200; Email: lfzhouc@fudan.edu.cn
    • Sub-Investigator: Nijiati Kudulaiti, M.D.
    • Principal Investigator: Dongxiao Zhuang, M.D. Ph.D.
    • Sub-Investigator: Zhemin Huang, M.D.
    • Sub-Investigator: Chengjun Yao, M.D. Ph.D.
    • Sub-Investigator: Tainming Qiu, M.D. Ph.D.
    • Sub-Investigator: Junfeng Lu, M.D. Ph.D.
    • Sub-Investigator: Huiwei Zhang, M.D.
    • Sub-Investigator: Zhengwei Zhang, M.D.
    • Principal Investigator: Yihui Guan, M.D. Ph.D.
    • Principal Investigator: Jingsong Wu, M.D. Ph.D.
    • Sub-Investigator: Zhifeng Shi, M.D. Ph.D.
    • Sub-Investigator: Jie Zhang, M.D. Ph.D.
    • Sub-Investigator: Fangyuan Gong, M.D.
    • Sub-Investigator: Zhengda Yv, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinical manifestations and imaging examination (CT, MRI, et al) are in accordance with high grade glioma
2. No PET/CT scanning contraindications
3. No MRI scanning contraindications
4. Patients older than 18 years old
5. ECOG score between 0 to 2
6. Patients with sufficient bone marrow, kidney and liver function reserve.
7. All patients gave written informed consent.

Exclusion Criteria:

1. Patient who has received immune therapy, radiation therapy, chemotherapy, hormone drugs, biological products or other clinical trials within 14 days.
2. Patient who has received EGFR monoclonal antibody therapy within 4 weeks.
3. Patients who has not fully recovered form the past drug toxicity reaction (CTCAE in grade 2 or above).
4. Patient who has received major surgery within 7 days.
5. Patients with allergies to immunoglobulin.
6. Breastfeeding women.
7. pregnant women
8. Patients with severe clinical condition.
9. Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: High Grade Glioma; We plan to perform PET scanning on the patients with high grade gliomas after the injection of the second generation of EGFR tracer ,89Zr-ABT806（1-2mCi）, which can be specifically binded to EGFR vⅢ . After fusing the PET and MRI images, we precisely obtained the tissue from the"hot-spot" on the PET image through multimodal-neuronavigation-guided tumor biopsy. EGFRvⅢ status was detected by Sanger sequencing to analyze the correlation with the 89Zr-ABT806 PET image qualitatively and quantitatively. The final goal was to detect EGFR vⅢ by noninvasive molecular imaging procedure for the clinical outcome prediction and the selection of EGFR-targeted therapies.

Diagnostic test: 89Zr-ABT806 PET; Patients will be given IV bolus injection of 89Zr-ABT806(1-2mCi). The first 89Zr-ABT806 PET scan will be performed about 72 to 120 hours after injection of tracer. The second 89Zr-ABT806 PET scan will be performed about 120 to 168 hours after injection of tracer. Semi-quantitative analysis was performed using the maximum standardized uptake value (SUVmax) and T/N ratio.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The sensitivity and specificity of 89Zr-ABT806 PET	After fusing the 89Zr-ABT806 PET and MRI images, investigators precisely obtained the tissue from the"hot-spot" on the PET image through multimodal-neuronavigation-guided tumor biopsy. EGFRvⅢ status will be analyzed by molecular methods. The sensitivity and specificity of 89Zr-ABT806 PET will be measured with statistic methods.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The overall survival time of participants	regular follow-up	4 years
The progression-free survival time of participants	regular follow-up	4 year
The correlation between EGFRvIII mutation and prognosis of participants		4 year

Collaborators and Investigators

• Sponsor: Huashan Hospital

Publications and helpful links

General Publications

• Wong AJ, Ruppert JM, Bigner SH, Grzeschik CH, Humphrey PA, Bigner DS, Vogelstein B. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2965-9. doi: 10.1073/pnas.89.7.2965.
• Ekstrand AJ, James CD, Cavenee WK, Seliger B, Pettersson RF, Collins VP. Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res. 1991 Apr 15;51(8):2164-72.
• Libermann TA, Razon N, Bartal AD, Yarden Y, Schlessinger J, Soreq H. Expression of epidermal growth factor receptors in human brain tumors. Cancer Res. 1984 Feb;44(2):753-60.
• Sugawa N, Ekstrand AJ, James CD, Collins VP. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8602-6. doi: 10.1073/pnas.87.21.8602.
• Yamazaki H, Fukui Y, Ueyama Y, Tamaoki N, Kawamoto T, Taniguchi S, Shibuya M. Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors. Mol Cell Biol. 1988 Apr;8(4):1816-20. doi: 10.1128/mcb.8.4.1816-1820.1988.
• Malden LT, Novak U, Kaye AH, Burgess AW. Selective amplification of the cytoplasmic domain of the epidermal growth factor receptor gene in glioblastoma multiforme. Cancer Res. 1988 May 15;48(10):2711-4.
• Ekstrand AJ, Sugawa N, James CD, Collins VP. Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4309-13. doi: 10.1073/pnas.89.10.4309.
• Nagane M, Coufal F, Lin H, Bogler O, Cavenee WK, Huang HJ. A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res. 1996 Nov 1;56(21):5079-86.
• Batra SK, Castelino-Prabhu S, Wikstrand CJ, Zhu X, Humphrey PA, Friedman HS, Bigner DD. Epidermal growth factor ligand-independent, unregulated, cell-transforming potential of a naturally occurring human mutant EGFRvIII gene. Cell Growth Differ. 1995 Oct;6(10):1251-9.
• Nishikawa R, Ji XD, Harmon RC, Lazar CS, Gill GN, Cavenee WK, Huang HJ. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7727-31. doi: 10.1073/pnas.91.16.7727.
• Pedersen MW, Tkach V, Pedersen N, Berezin V, Poulsen HS. Expression of a naturally occurring constitutively active variant of the epidermal growth factor receptor in mouse fibroblasts increases motility. Int J Cancer. 2004 Feb 20;108(5):643-53. doi: 10.1002/ijc.11566.
• Lammering G, Hewit TH, Holmes M, Valerie K, Hawkins W, Lin PS, Mikkelsen RB, Schmidt-Ullrich RK. Inhibition of the type III epidermal growth factor receptor variant mutant receptor by dominant-negative EGFR-CD533 enhances malignant glioma cell radiosensitivity. Clin Cancer Res. 2004 Oct 1;10(19):6732-43. doi: 10.1158/1078-0432.CCR-04-0393.
• Lammering G, Valerie K, Lin PS, Hewit TH, Schmidt-Ullrich RK. Radiation-induced activation of a common variant of EGFR confers enhanced radioresistance. Radiother Oncol. 2004 Sep;72(3):267-73. doi: 10.1016/j.radonc.2004.07.004.
• Feldkamp MM, Lala P, Lau N, Roncari L, Guha A. Expression of activated epidermal growth factor receptors, Ras-guanosine triphosphate, and mitogen-activated protein kinase in human glioblastoma multiforme specimens. Neurosurgery. 1999 Dec;45(6):1442-53. doi: 10.1097/00006123-199912000-00034.
• Emrich JG, Brady LW, Quang TS, Class R, Miyamoto C, Black P, Rodeck U. Radioiodinated (I-125) monoclonal antibody 425 in the treatment of high grade glioma patients: ten-year synopsis of a novel treatment. Am J Clin Oncol. 2002 Dec;25(6):541-6. doi: 10.1097/00000421-200212000-00001.
• Li G, Wong AJ. EGF receptor variant III as a target antigen for tumor immunotherapy. Expert Rev Vaccines. 2008 Sep;7(7):977-85. doi: 10.1586/14760584.7.7.977.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2017
• Primary Completion (ANTICIPATED): December 1, 2018
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: February 11, 2017
• First Submitted That Met QC Criteria: February 15, 2017
• First Posted (ACTUAL): February 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 20, 2017
• Last Update Submitted That Met QC Criteria: February 15, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Glioma; PET; Molecular pathology; PET-CT; Neuronavigation; EGFR vIII; Multimodal neuronavigation
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: 81672476

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No