Carmustine Wafer in Combination With Retifanlimab and Radiation With/Without Temozolomide in Subjects With Glioblastoma
Carmustine Wafer in Combination With Retifanlimab and Radiation With/Without Temozolomide in Subjects With Glioblastoma
The purpose of the study is to evaluate the safety and survival of carmustine wafers and radiation and retifanlimab with or without temozolomide (TMZ) in newly-diagnosed adult subjects with glioblastoma multiform after carmustine wafer placement.
Neuro-Oncology,
Phase I
Phase I
Adults
Mol. targeted/Immunotherapy/Biologics,
Radiotherapy
Not Available
Thompson, Reid
National
Vanderbilt University
12-08-2023
Eligibility
18 Years to 100 Years
ALL
false
Inclusion Criteria:
Newly-diagnosed adults with WHO (World Health Organization) Grade IV Glioblastoma or gliosarcoma based on histopathological or molecular criteria who had carmustine wafers placed at resection
Newly-diagnosed adults with WHO (World Health Organization) Grade IV Glioblastoma or gliosarcoma based on histopathological or molecular criteria who had carmustine wafers placed at resection
No prior treatment for GBM other than surgical resection and carmustine wafer placement (Patients who had a biopsy prior to resection are allowed)
No prior treatment for GBM other than surgical resection and carmustine wafer placement (Patients who had a biopsy prior to resection are allowed)
Post-operative MRI or CT scan within 72 hours (preferably 24 hours) of surgical resection
Post-operative MRI or CT scan within 72 hours (preferably 24 hours) of surgical resection
Substantial recovery from surgical resection
Substantial recovery from surgical resection
On a stable or decreasing dose of steroids
On a stable or decreasing dose of steroids
Karnofsky Performance Status of 60
Karnofsky Performance Status of 60
Clinically appropriate for concomitant temozolomide plus radiation therapy (RT) based on institutional guidelines
Clinically appropriate for concomitant temozolomide plus radiation therapy (RT) based on institutional guidelines
Age 18 years
Age 18 years
Ensure that pregnant or lactating females are not enrolled and that contraceptive requirements are in accordance with applicable and recent requirements.
Ensure that pregnant or lactating females are not enrolled and that contraceptive requirements are in accordance with applicable and recent requirements.
Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 180 days after the last dose of retifanlimab
Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 180 days after the last dose of retifanlimab
Must have normal organ and marrow function on routine laboratory tests
Must have normal organ and marrow function on routine laboratory tests
Ability to understand and the willingness to sign a written informed consent document
Ability to understand and the willingness to sign a written informed consent document
Subjects must be willing and able to comply with scheduled visits, treatment schedule, study procedures, and other requirements of the study
Subjects must be willing and able to comply with scheduled visits, treatment schedule, study procedures, and other requirements of the study
Exclusion Criteria:
Recurrent glioblastoma (GBM) or progression of lower grade tumor
Recurrent glioblastoma (GBM) or progression of lower grade tumor
Central nervous system (CNS) hemorrhage of Grade > 1 on baseline MRI scan, unless subsequently documented to have resolved
Central nervous system (CNS) hemorrhage of Grade > 1 on baseline MRI scan, unless subsequently documented to have resolved
Any known metastatic extracranial or leptomeningeal disease
Any known metastatic extracranial or leptomeningeal disease
Intent to use other anti-neoplastic medications/treatments including the Optune device
Intent to use other anti-neoplastic medications/treatments including the Optune device
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
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
Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
Active, known or suspected autoimmune disease, with the following exceptions: Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment (subjects with a history of flares requiring systemic treatment are excluded), or other autoimmune conditions not expected to recur in the absence of an external trigger are permitted to enroll
Active, known or suspected autoimmune disease, with the following exceptions: Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment (subjects with a history of flares requiring systemic treatment are excluded), or other autoimmune conditions not expected to recur in the absence of an external trigger are permitted to enroll
Subjects with history of life-threatening toxicity, including hypersensitivity reaction, related to prior immunoglobulin treatment for another condition (except those considered unlikely to re-occur, with written approval of study PI) or any other study drug component
Subjects with history of life-threatening toxicity, including hypersensitivity reaction, related to prior immunoglobulin treatment for another condition (except those considered unlikely to re-occur, with written approval of study PI) or any other study drug component
History or evidence upon physical/neurological examination of other central nervous system condition (e.g., seizures, abscess) unrelated to cancer, unless adequately controlled by medication or considered not potentially interfering with protocol treatment
History or evidence upon physical/neurological examination of other central nervous system condition (e.g., seizures, abscess) unrelated to cancer, unless adequately controlled by medication or considered not potentially interfering with protocol treatment
Surgical procedure 7 days prior to study treatment (No restriction for insertion of a central venous access device)
Surgical procedure 7 days prior to study treatment (No restriction for insertion of a central venous access device)
Unable to swallow oral medication or any gastrointestinal disease or surgical procedure that may seriously impact the absorption of temozolomide
Unable to swallow oral medication or any gastrointestinal disease or surgical procedure that may seriously impact the absorption of temozolomide
Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, totally excised melanoma of stage IIA or lower, low or intermediate-grade localized prostate cancer (Gleason score 7), and curatively-treated carcinoma in situ of the cervix, breast, or bladder.
Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, totally excised melanoma of stage IIA or lower, low or intermediate-grade localized prostate cancer (Gleason score 7), and curatively-treated carcinoma in situ of the cervix, breast, or bladder.
Known history of any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus
Known history of any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus
Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities (to Grade >1 or baseline), not require corticosteroids for this purpose, and not have had radiation pneumonitis.
Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities (to Grade >1 or baseline), not require corticosteroids for this purpose, and not have had radiation pneumonitis.
Toxicity of prior therapy that has not recovered to Grade 1 or baseline (with the exception of any grade of alopecia and anemia not requiring transfusion support).
Toxicity of prior therapy that has not recovered to Grade 1 or baseline (with the exception of any grade of alopecia and anemia not requiring transfusion support).
Participants with specified abnormal laboratory values at screening
Participants with specified abnormal laboratory values at screening
Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent). * Physiologic corticosteroid replacement therapy at doses 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted. * Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate. * Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate. * Brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy) or study treatment-related standard premedication is permitted.
Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent). * Physiologic corticosteroid replacement therapy at doses 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted. * Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate. * Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate. * Brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy) or study treatment-related standard premedication is permitted.
Has an active infection requiring systemic antibiotics or antifungal treatment
Has an active infection requiring systemic antibiotics or antifungal treatment
History of organ transplant, including allogeneic stem cell transplantation
History of organ transplant, including allogeneic stem cell transplantation
Known allergy or hypersensitivity to any component of retifanlimab or formulation components
Known allergy or hypersensitivity to any component of retifanlimab or formulation components
Has received a live vaccine within 28 days of the planned start of study drug (Note: Examples of live vaccines include but are not limited to measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus of Calmette and Guerin (BCG), and typhoid vaccine. Inactivated seasonal influenza vaccines and COVID-19 vaccine(s) are permitted and do not require a 4-week waiting period before starting study treatment; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.)
Has received a live vaccine within 28 days of the planned start of study drug (Note: Examples of live vaccines include but are not limited to measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus of Calmette and Guerin (BCG), and typhoid vaccine. Inactivated seasonal influenza vaccines and COVID-19 vaccine(s) are permitted and do not require a 4-week waiting period before starting study treatment; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.)
Patients who are taking Probiotic dietary supplements
Patients who are taking Probiotic dietary supplements
Patients with uncontrolled intercurrent illness
Patients with uncontrolled intercurrent illness
Patients with psychiatric illness/social situations (e.g. prisoners/involuntarily incarcerated individuals) that would limit compliance with study requirements
Patients with psychiatric illness/social situations (e.g. prisoners/involuntarily incarcerated individuals) that would limit compliance with study requirements
Newly-diagnosed adults with WHO (World Health Organization) Grade IV Glioblastoma or gliosarcoma based on histopathological or molecular criteria who had carmustine wafers placed at resection
Newly-diagnosed adults with WHO (World Health Organization) Grade IV Glioblastoma or gliosarcoma based on histopathological or molecular criteria who had carmustine wafers placed at resection
No prior treatment for GBM other than surgical resection and carmustine wafer placement (Patients who had a biopsy prior to resection are allowed)
No prior treatment for GBM other than surgical resection and carmustine wafer placement (Patients who had a biopsy prior to resection are allowed)
Post-operative MRI or CT scan within 72 hours (preferably 24 hours) of surgical resection
Post-operative MRI or CT scan within 72 hours (preferably 24 hours) of surgical resection
Substantial recovery from surgical resection
Substantial recovery from surgical resection
On a stable or decreasing dose of steroids
On a stable or decreasing dose of steroids
Karnofsky Performance Status of 60
Karnofsky Performance Status of 60
Clinically appropriate for concomitant temozolomide plus radiation therapy (RT) based on institutional guidelines
Clinically appropriate for concomitant temozolomide plus radiation therapy (RT) based on institutional guidelines
Age 18 years
Age 18 years
Ensure that pregnant or lactating females are not enrolled and that contraceptive requirements are in accordance with applicable and recent requirements.
Ensure that pregnant or lactating females are not enrolled and that contraceptive requirements are in accordance with applicable and recent requirements.
Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 180 days after the last dose of retifanlimab
Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 180 days after the last dose of retifanlimab
Must have normal organ and marrow function on routine laboratory tests
Must have normal organ and marrow function on routine laboratory tests
Ability to understand and the willingness to sign a written informed consent document
Ability to understand and the willingness to sign a written informed consent document
Subjects must be willing and able to comply with scheduled visits, treatment schedule, study procedures, and other requirements of the study
Subjects must be willing and able to comply with scheduled visits, treatment schedule, study procedures, and other requirements of the study
Exclusion Criteria:
Recurrent glioblastoma (GBM) or progression of lower grade tumor
Recurrent glioblastoma (GBM) or progression of lower grade tumor
Central nervous system (CNS) hemorrhage of Grade > 1 on baseline MRI scan, unless subsequently documented to have resolved
Central nervous system (CNS) hemorrhage of Grade > 1 on baseline MRI scan, unless subsequently documented to have resolved
Any known metastatic extracranial or leptomeningeal disease
Any known metastatic extracranial or leptomeningeal disease
Intent to use other anti-neoplastic medications/treatments including the Optune device
Intent to use other anti-neoplastic medications/treatments including the Optune device
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
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
Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
Active, known or suspected autoimmune disease, with the following exceptions: Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment (subjects with a history of flares requiring systemic treatment are excluded), or other autoimmune conditions not expected to recur in the absence of an external trigger are permitted to enroll
Active, known or suspected autoimmune disease, with the following exceptions: Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment (subjects with a history of flares requiring systemic treatment are excluded), or other autoimmune conditions not expected to recur in the absence of an external trigger are permitted to enroll
Subjects with history of life-threatening toxicity, including hypersensitivity reaction, related to prior immunoglobulin treatment for another condition (except those considered unlikely to re-occur, with written approval of study PI) or any other study drug component
Subjects with history of life-threatening toxicity, including hypersensitivity reaction, related to prior immunoglobulin treatment for another condition (except those considered unlikely to re-occur, with written approval of study PI) or any other study drug component
History or evidence upon physical/neurological examination of other central nervous system condition (e.g., seizures, abscess) unrelated to cancer, unless adequately controlled by medication or considered not potentially interfering with protocol treatment
History or evidence upon physical/neurological examination of other central nervous system condition (e.g., seizures, abscess) unrelated to cancer, unless adequately controlled by medication or considered not potentially interfering with protocol treatment
Surgical procedure 7 days prior to study treatment (No restriction for insertion of a central venous access device)
Surgical procedure 7 days prior to study treatment (No restriction for insertion of a central venous access device)
Unable to swallow oral medication or any gastrointestinal disease or surgical procedure that may seriously impact the absorption of temozolomide
Unable to swallow oral medication or any gastrointestinal disease or surgical procedure that may seriously impact the absorption of temozolomide
Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, totally excised melanoma of stage IIA or lower, low or intermediate-grade localized prostate cancer (Gleason score 7), and curatively-treated carcinoma in situ of the cervix, breast, or bladder.
Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, totally excised melanoma of stage IIA or lower, low or intermediate-grade localized prostate cancer (Gleason score 7), and curatively-treated carcinoma in situ of the cervix, breast, or bladder.
Known history of any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus
Known history of any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus
Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities (to Grade >1 or baseline), not require corticosteroids for this purpose, and not have had radiation pneumonitis.
Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment. Note: Participants must have recovered from all radiation-related toxicities (to Grade >1 or baseline), not require corticosteroids for this purpose, and not have had radiation pneumonitis.
Toxicity of prior therapy that has not recovered to Grade 1 or baseline (with the exception of any grade of alopecia and anemia not requiring transfusion support).
Toxicity of prior therapy that has not recovered to Grade 1 or baseline (with the exception of any grade of alopecia and anemia not requiring transfusion support).
Participants with specified abnormal laboratory values at screening
Participants with specified abnormal laboratory values at screening
Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent). * Physiologic corticosteroid replacement therapy at doses 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted. * Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate. * Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate. * Brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy) or study treatment-related standard premedication is permitted.
Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent). * Physiologic corticosteroid replacement therapy at doses 10 mg/day of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted. * Participants with asthma that requires intermittent use of bronchodilators, inhaled steroids, or local steroid injections may participate. * Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may participate. * Brief courses of corticosteroids for prophylaxis (e.g., contrast dye allergy) or study treatment-related standard premedication is permitted.
Has an active infection requiring systemic antibiotics or antifungal treatment
Has an active infection requiring systemic antibiotics or antifungal treatment
History of organ transplant, including allogeneic stem cell transplantation
History of organ transplant, including allogeneic stem cell transplantation
Known allergy or hypersensitivity to any component of retifanlimab or formulation components
Known allergy or hypersensitivity to any component of retifanlimab or formulation components
Has received a live vaccine within 28 days of the planned start of study drug (Note: Examples of live vaccines include but are not limited to measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus of Calmette and Guerin (BCG), and typhoid vaccine. Inactivated seasonal influenza vaccines and COVID-19 vaccine(s) are permitted and do not require a 4-week waiting period before starting study treatment; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.)
Has received a live vaccine within 28 days of the planned start of study drug (Note: Examples of live vaccines include but are not limited to measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus of Calmette and Guerin (BCG), and typhoid vaccine. Inactivated seasonal influenza vaccines and COVID-19 vaccine(s) are permitted and do not require a 4-week waiting period before starting study treatment; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.)
Patients who are taking Probiotic dietary supplements
Patients who are taking Probiotic dietary supplements
Patients with uncontrolled intercurrent illness
Patients with uncontrolled intercurrent illness
Patients with psychiatric illness/social situations (e.g. prisoners/involuntarily incarcerated individuals) that would limit compliance with study requirements
Patients with psychiatric illness/social situations (e.g. prisoners/involuntarily incarcerated individuals) that would limit compliance with study requirements
