Personalized Trial in ctDNA-level-relapse Glioblastoma

NCT05539339 | Unknown

• 1 other identifier: HPPH-ttrGBM
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Tumor in situ fluid (TISF) refers to the fluid within the surgical cavity of patients with glioblastoma. Postoperative serial TISF is collected for circulating tumor DNA (ctDNA) analysis and identifying ctDNA-level relapse driven by one or a set of specific genomic alterations before overt imaging recurrence of the tumor. This single-arm open-label prospective pilot feasibility trial recruiting 20 adult patients with ctDNA-level-relapse glioblastoma who are assigned to receive the personalized study treatment based on the genetic profile of their serial TISF ctDNA. It will be aimed to test whether the personalized intervention can prolong the progression-free and overall survival and the feasibility of conducting a full-scale trial.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Progression-free survival at 6 months

  The proportion of participants in the analysis population who remain progression-free for at least six months following initiation of study therapy.

  Up to six months after beginning treatment

• Overall survival rate at 18 months

  OS-18 is the proportion of participants in the analysis population who remain alive for at least twelve months following initiation of study therapy.

  Up to 18 months after beginning therapy

Secondary Outcomes (2)

• Overall survival

  Up to 3 years after beginning treatment

• Progression-free survival

  Up to 3 years after beginning treatment

Study Arms (1)

Arm 1

EXPERIMENTAL

This arm includes patients with ctDNA-level-relapse glioblastoma before imaging recurrence.

Other: Individualized intervention based on genomic alterations

Interventions

Individualized intervention based on genomic alterations OTHER

Specialized tumor board recommended agents that target the specific recurrence-driving genomic alterations that are determined by serial TISF ctDNA analysis.

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study, including disease assessment by MRI and tumor in situ fluid (TISF) collection
• Histologically confirmed diagnosis of glioblastoma
• Resection surgery done at the study center (Henan Provincial People's Hospital), with a reservoir intraoperatively implanted connecting the surgical cavity and the subscalp for postoperative noninvasive TISF collection
• Previous first line treatment with at least radiotherapy
• An interval of \> 28 days and full recovery (i.e., no ongoing safety issues) from surgical resection prior to grouping
• Karnofsky performance status (KPS) of 70 or higher
• Life expectancy \> 12 weeks

You may not qualify if:

• More than two recurrences of GBM
• Presence of extracranial metastatic, significant leptomeningeal disease or tumors primarily localized to the brainstem or spinal cord
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring chronic and systemic immunosuppressive treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects have any other condition requiring systemic treatment with corticosteroids or other immunosuppressive agents within 14 days. Inhaled or topical steroids and adrenal replacement doses \>10mg daily prednisone equivalent are permitted in absence of active autoimmune disease
• Previous radiation therapy with anything other than standard radiation therapy (i.e., focally directed radiation) administered as first line therapy
• Previous treatment with carmustine wafer except when administered as first line treatment and at least 6 months prior to randomization
• Previous bevacizumab or other VEGF or anti-angiogenic treatment
• Previous treatment with a PD-1, PD-L1 or CTLA-4 targeted therapy
• Evidence of \> Grade 1 CNS hemorrhage on the baseline MRI scan
• Inadequately controlled hypertension (defined as systolic blood pressure ≥160 mmHg and /or diastolic blood pressure ≥100 mmHg) within 7 days of first study treatment
• Prior history of hypertensive crisis, hypertensive encephalopathy, reversible posterior leukoencephalopathy syndrome (RPLS)
• Prior history of gastrointestinal diverticulitis, perforation, or abscess
• Clinically significant (i.e., active) cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment. Any previous venous thromboembolism ≥ NCI CTCAE Grade 3 within 3 months prior to start of study treatment
• History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 1 month prior to randomization

Sponsors & Collaborators

• Henan Provincial People's Hospital: lead

Study Sites (1)

Henan Provincial People's Hospital

Zhengzhou, Henan, 450003, China

Location

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Xingyao Bu, MD, PhD

  Henan Provincial People's Hospital

  STUDY DIRECTOR

Central Study Contacts

Xingyao Bu, MD, PhD

CONTACT

+86037165580295; xingyaob@zzu.edu.cn

Zhiyuan Sheng, MD

CONTACT

+86037165580295; zhiyuan.sheng22@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, pilot, umbrella trial

Study Record Dates

• First Submitted: September 10, 2022
• First Posted: September 14, 2022
• Study Start: December 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2025
• Last Updated: September 27, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)