Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioma

Glioblastoma

Disease Attributes

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Mitoguazone

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

ARM I: Patients receive retifanlimab IV over 30 minutes on day 1 and bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT QD, starting in cycle 1 on day 15 for 10 treatments. Patients undergo MRI or CT, as well as blood sample collection throughout the study.

Patients receive bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT QD, starting in cycle 1 on day 15 for 10 treatments. Patients undergo MRI or CT, as well as blood sample collection throughout the study.

Biospecimen Collection

Computed Tomography

Electronic Health Record Review

Hypofractionated Radiation Therapy

Magnetic Resonance Imaging

Retifanlimab

Jian L. Campian

Jian L Campian

This phase II trial tests how well retifanlimab with bevacizumab and hypofractionated radiotherapy, compared to bevacizumab and hypofractionated radiotherapy alone, works in treating patients with glioblastoma that has come back after a period of improvement (recurrent). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving retifanlimab with bevacizumab and hypofractionated radiotherapy may work better in treating patients with recurrent glioblastoma than bevacizumab and hypofractionated radiotherapy alone.

PRIMARY OBJECTIVE:

I. To investigate the overall survival at 9 months (OS-9) of the combination of retifanlimab, bevacizumab and hypofractionated radiation therapy (HFRT) vs. the control group treated with bevacizumab and HFRT.

SECONDARY OBJECTIVES:

I. To assess the overall survival (OS) in this patient population for each regimen.

II. To assess the progression free survival (PFS) in this patient population for each regimen.

III. To assess the objective response rate (ORR) in this patient population for each regimen.

IV. To assess the neurologic function by Neurologic Assessment in Neuro-Oncology (NANO) in this patient population for each regimen.

V. To assess the frequency and severity of adverse events in this patient population for each regimen.

CORRELATIVE OBJECTIVE:

I. To assess the anti-glioma immune response before and after retifanlimab including assessment of immune cells phenotyping, function and activation in the pre-/post-treatment blood, and changes in cytokine levels over time.

OUTLINE: Patients are randomized to 1 of 2 arms

ARM A: Patients receive retifanlimab intravenously (IV) over 30 minutes on day 1 and bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT once daily (QD), starting in cycle 1 on day 15 for 10 treatments. Patients undergo magnetic resonance imaging (MRI) or computed tomography (CT), as well as blood sample collection throughout the study.

ARM B: Patients receive bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT QD, starting in cycle 1 on day 15 for 10 treatments. Patients undergo MRI or CT, as well as blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days. Survival follow-up is every 2 months for the first year, and then every 6 months for up to 4 years from registration.

Retifanlimab With Bevacizumab and Hypofractionated Radiotherapy for the Treatment of Recurrent Glioblastoma

A Phase II Open Label, Randomized Study Testing the Efficacy of Retifanlimab in Combination With Bevacizumab and Hypofractionated Radiotherapy in Patients With Recurrent GBM

Defined as the proportion of patients who are alive 9 months after randomization based on Kaplan Meier estimate. The proportion of patients alive will be compared between treatment arms using a z-score test statistic. The 9-month OS Kaplan Meier estimate and corresponding 95% confidence interval for each arm will be reported.

Overall survival is defined as the time from registration to death from any cause. OS will be estimated using the Kaplan-Meier method. The logrank test will be used to compare the distribution between treatment arms. The median OS and corresponding 95% confidence interval (by Brookmeyer and Crowley) will be reported for each treatment arm.

Progression free survival is defined as the time from randomization to documentation of disease progression or death due to any cause, whichever is first. The distribution of PFS will be estimated using the method of Kaplan-Meier. PFS will be compared between the 2 treatment arms using the log-rank test. The median PFS and corresponding 95% confidence intervals will be reported.

Objective response is defined as experiencing a complete response (CR) or partial response (PR) (as defined by RANO criteria, see section 11.0) while on protocol treatment. Objective response rate (ORR) is defined as the number of patients who experience objective response divided by the number of patients in the primary analysis population. ORR will be compared between the 2 treatment arms. Confidence intervals for ORR will be calculated according to the approach of Clopper and Pearson. Overall response rate and the corresponding 95% confidence interval will be reported.

Neurologic function domain scores of the Neurologic Assessment in Neuro-Oncology be summarized by descriptive statistics including mean, median, standard deviation, and range for each regimen at each time point. The difference between baseline and 2 months (1st restaging scan) will be compared using a Wilcoxon Rank Sum test across arm for each domain. The median difference for each domain and 1st and 3rd quartile will be reported for each arm.

The overall adverse event rates for grade 3 or higher adverse events will be reported.

National Cancer Institute (NCI)

Academic and Community Cancer Research United

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receive triapine PO QD for 5 days prior to surgical resection. After surgical resection, patients receive temozolomide PO QD and triapine PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI at screening and on study and undergo collection of blood samples on study.

Patients receive temozolomide PO QD and triapine PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI at screening and on study and undergo collection of blood samples on study.

Questionnaire Administration

Resection

Triapine

Study Coordinator

Karan Dixit

Karan Dixit, MD

This phase I trial tests the safety, side effects, and best dose of triapine in combination with temozolomide in treating patients with glioblastoma that has come back after a period of improvement (recurrent). Triapine inhibits an enzyme responsible for producing molecules required for the production of deoxyribonucleic acid (DNA), which may inhibit tumor cell growth. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Giving triapine in combination with temozolomide may be safe, tolerable, and/or effective in treating patients with recurrent glioblastoma.

PRIMARY OBJECTIVE:

I. To evaluate the recommended phase 2 dose (RP2D) for triapine (3-AP) in combination with temozolomide (TMZ).

SECONDARY OBJECTIVES:

I. To evaluate the safety profile of triapine in combination with temozolomide (TMZ).

II. To evaluate progression-free survival (PFS). III. To evaluate overall survival (OS). IV. To evaluate the overall response rate (ORR) per Response Assessment in Neuro-Oncology (RANO) criteria.

EXPLORATORY OBJECTIVES:

I. To investigate the distribution of triapine within tumor and peritumoral areas post oral administration and correlation with serum levels.

II. To investigate the potential interaction of drug absorption when administrating oral triapine and temozolomide together by measuring plasma levels triapine and temozolomide post administration.

III. To evaluate oral triapine plasma pharmacokinetics and corresponding methemoglobin level by venous blood gas proportion.

IV. To evaluate the quality of life per Functional Assessment of Cancer Therapy-Brain (FACT-Br) for patients treated with triapine and temozolomide.

OUTLINE: This is a dose-escalation study of triapine in combination with temozolomide. Patients with recurrent glioblastoma not planning to undergo surgery are assigned to group 1 or group 2. Patients with recurrent glioblastoma planning to undergo surgery are assigned to group 3.

GROUPS 1 AND 2: Patients receive temozolomide orally (PO) once daily (QD) and triapine PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) at screening and on study and undergo collection of blood samples on study.

GROUP 3: Patients receive triapine PO QD for 5 days prior to surgical resection. After surgical resection, patients receive temozolomide PO QD and triapine PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI at screening and on study and undergo collection of blood samples on study.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 24 months.

Triapine in Combination With Temozolomide for the Treatment of Patients With Recurrent Glioblastoma

A Phase 1 Adaptive Dose Escalation With Dose Expansion Study of Triapine in Combination With Temozolomide (TMZ) for Patients With Recurrent Glioblastoma

The recommended phase 2 dose will be based on treatment-emergent and drug-related toxicity. Dose limiting toxicities and adverse events (AEs) will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0.

Will evaluate the occurrence of toxicity (AEs and serious AEs) and the number of patients who discontinue treatment due to toxicity. Toxicity will be assessed by CTCAE v. 5.0. Adverse events will be sorted (by type, severity \[grade\], timing, and attribution to triapine), collected, and reported according to CTCAE v5.0.

Progression will be determined by clinical progression or by radiographic imaging as assessed by Response Assessment in Neuro-Oncology (RANO) criteria. The median and corresponding 95% confidence interval will also be estimated.

Will be described by Kaplan-Meier curve. The median and corresponding 95% confidence interval will also be estimated.

ORR will be assessed by RANO criteria. To determine the ORR, this endpoint will calculate the proportion of treated patients who experience an overall response (complete response \[CR\] or partial response \[PR\] per RANO criteria). The date of first response for either CR or PR will be used for the calculation of ORR. Will be estimated using the expansion cohort, along with its 95% confidence interval.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Retifanlimab With Bevacizumab and Hypofractionated Radiotherapy for the Treatment of Recurrent Glioblastoma	NCT06160206	Recurrent Gliob... Recurrent WHO G...	Bevacizumab Biospecimen Col... Computed Tomogr... Electronic Heal... Hypofractionate... Magnetic Resona... Retifanlimab	18 Years -	Academic and Community Cancer Research United
Retifanlimab With Bevacizumab and Hypofractionated Radiotherapy for the Treatment of Recurrent Glioblastoma	NCT06160206	Recurrent Gliob... Recurrent WHO G...	Bevacizumab Biospecimen Col... Computed Tomogr... Electronic Heal... Hypofractionate... Magnetic Resona... Retifanlimab	18 Years -	Academic and Community Cancer Research United
Triapine in Combination With Temozolomide for the Treatment of Patients With Recurrent Glioblastoma	NCT06410248	Recurrent Gliob... Recurrent WHO G... Recurrent WHO G... Recurrent WHO G...	Biospecimen Col... Magnetic Resona... Questionnaire A... Resection Temozolomide Triapine	18 Years -	Northwestern University

Spots Global Cancer Trial Database for recurrent who grade 4 glioma