RECRUITING

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

Conditions

Recurrent Glioblastoma Recurrent WHO Grade 4 Glioma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-10-02

Study Completion:2030-11-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06160206

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age ≥ 18 years * Recurrent World Health Organization (WHO) grade IV glioblastoma. Note: Any number of recurrences are allowable. Glioblastoma (GBM) variants and molecular GBM are allowed * Candidates for radiotherapy * Prior use of bevacizumab is allowed as long as the last treatment is \> 4 months prior to randomization * Dexamethasone dose ≤ 4mg daily at the time of randomization (higher dose of steroid for symptom control is allowed during the study) * Karnofsky performance status ≥ 60% * Measurable disease or non-measurable disease per Response Assessment in Neuro-Oncology (RANO) criteria * Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 (obtained ≤ 28 days prior to registration) * NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the Academic and Community Cancer Research Untied (ACCRU) website under "General Forms" * Platelet count ≥ 100,000/mm\^3 (obtained ≤ 28 days prior to registration) * NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms" * Hemoglobin ≥ 9.0 g/dL (obtained ≤ 28 days prior to registration) * NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms" * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 28 days prior to registration) * NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms" * Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 28 days prior to registration) * NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms" * Creatinine ≤ 1.5 x ULN (obtained ≤ 28 days prior to registration) * NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms" * Negative pregnancy test done ≤ 14 days prior to registration for women of childbearing potential only. (Pregnancy test can be urine or serum.) * NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * A female of childbearing potential is a sexually mature female who: * 1) Has not undergone a hysterectomy or bilateral hysterectomy; or * 2) Has not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months) * Provide informed written consent ≤ 28 days prior to registration * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study, i.e., active treatment) * Willing to provide mandatory blood specimens for correlative research purposes	* Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown: * Pregnant persons * Nursing persons * Persons of childbearing potential who are unwilling to employ adequate contraception (men and women) * Co-morbid systemic illness or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into the study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens * Receiving any other investigational agent which would be considered treatment for the primary neoplasm ≤ 2 weeks prior to registration * Active uncontrolled autoimmune disease or syndrome (i.e. moderate or severe rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, active inflammatory bowel disease) that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) or who are receiving systemic therapy for an autoimmune or inflammatory disease (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Subjects are permitted to enroll if they have vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger * Has a severe acute or chronic medical condition including immune colitis, inflammatory bowel disease (may be enrolled at the discretion of the principal investigator \[PI\]), immune pneumonitis, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to epacadostat, retifanlimab, bevacizumab, or other agents used in the study * Has had an allogeneic tissue/solid organ transplant * Has uncontrolled human immunodeficiency virus (HIV) (HIV ½ antibodies). Well-controlled HIV is defined as CD4+ count \> 300 cells, undetectable viral load, and receiving highly active antiretroviral therapy (HAART)/antiretroviral therapy (ART). Study specific HIV testing is not required for patients who do not have any prior history of HIV * Has uncontrolled active hepatitis B (HBV) (e.g., hepatitis B serum antigen \[HBsAg\] reactive or HBV dioxyribonucleic acid \[DNA\] detected by quant real time polymerase chain reaction \[RT PCR\]) or hepatitis C (e.g. hepatitis C serum antigen \[HCsAg\] reactive or hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative or quantitative\] is detected) * Receipt of live attenuated vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed

Inclusion Criteria

Exclusion Criteria

* Age ≥ 18 years
* Recurrent World Health Organization (WHO) grade IV glioblastoma. Note: Any number of recurrences are allowable. Glioblastoma (GBM) variants and molecular GBM are allowed
* Candidates for radiotherapy
* Prior use of bevacizumab is allowed as long as the last treatment is \> 4 months prior to randomization
* Dexamethasone dose ≤ 4mg daily at the time of randomization (higher dose of steroid for symptom control is allowed during the study)
* Karnofsky performance status ≥ 60%
* Measurable disease or non-measurable disease per Response Assessment in Neuro-Oncology (RANO) criteria
* Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 (obtained ≤ 28 days prior to registration)
* NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the Academic and Community Cancer Research Untied (ACCRU) website under "General Forms"
* Platelet count ≥ 100,000/mm\^3 (obtained ≤ 28 days prior to registration)
* NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms"
* Hemoglobin ≥ 9.0 g/dL (obtained ≤ 28 days prior to registration)
* NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms"
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 28 days prior to registration)
* NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms"
* Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 28 days prior to registration)
* NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms"
* Creatinine ≤ 1.5 x ULN (obtained ≤ 28 days prior to registration)
* NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms"
* Negative pregnancy test done ≤ 14 days prior to registration for women of childbearing potential only. (Pregnancy test can be urine or serum.)
* NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* A female of childbearing potential is a sexually mature female who:
* 1) Has not undergone a hysterectomy or bilateral hysterectomy; or
* 2) Has not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months)
* Provide informed written consent ≤ 28 days prior to registration
* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study, i.e., active treatment)
* Willing to provide mandatory blood specimens for correlative research purposes

* Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:
* Pregnant persons
* Nursing persons
* Persons of childbearing potential who are unwilling to employ adequate contraception (men and women)
* Co-morbid systemic illness or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into the study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
* Receiving any other investigational agent which would be considered treatment for the primary neoplasm ≤ 2 weeks prior to registration
* Active uncontrolled autoimmune disease or syndrome (i.e. moderate or severe rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, active inflammatory bowel disease) that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) or who are receiving systemic therapy for an autoimmune or inflammatory disease (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Subjects are permitted to enroll if they have vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
* Has a severe acute or chronic medical condition including immune colitis, inflammatory bowel disease (may be enrolled at the discretion of the principal investigator \[PI\]), immune pneumonitis, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to epacadostat, retifanlimab, bevacizumab, or other agents used in the study
* Has had an allogeneic tissue/solid organ transplant
* Has uncontrolled human immunodeficiency virus (HIV) (HIV ½ antibodies). Well-controlled HIV is defined as CD4+ count \> 300 cells, undetectable viral load, and receiving highly active antiretroviral therapy (HAART)/antiretroviral therapy (ART). Study specific HIV testing is not required for patients who do not have any prior history of HIV
* Has uncontrolled active hepatitis B (HBV) (e.g., hepatitis B serum antigen \[HBsAg\] reactive or HBV dioxyribonucleic acid \[DNA\] detected by quant real time polymerase chain reaction \[RT PCR\]) or hepatitis C (e.g. hepatitis C serum antigen \[HCsAg\] reactive or hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative or quantitative\] is detected)
* Receipt of live attenuated vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist) are live attenuated vaccines and are not allowed

Contacts and Locations

Study Contact

Inbox Mayo Clinic Cancer Studies

CONTACT

507-538-5424

MAYOCLINICCANCERSTUDIES@mayo.edu

Mayo Clinic Cancer Studies

CONTACT

507-266-5822

MAYOCLINICCANCERSTUDIES@mayo.edu

Principal Investigator

Jian L Campian

PRINCIPAL_INVESTIGATOR

Academic and Community Cancer Research United

Study Locations (Sites)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259

United States

Mayo Clinic in Florida

Jacksonville, Florida, 32224

United States

Mayo Clinic

Rochester, Minnesota, 55905

United States

Collaborators and Investigators

Sponsor: Academic and Community Cancer Research United

Jian L Campian, PRINCIPAL_INVESTIGATOR, Academic and Community Cancer Research United

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-10-02

Study Completion Date2030-11-30

Study Record Updates

Study Start Date2024-10-02

Study Completion Date2030-11-30

Terms related to this study

Additional Relevant MeSH Terms

Recurrent Glioblastoma
Recurrent WHO Grade 4 Glioma