Ipilimumab, Nivolumab, and Ciforadenant as First-Line Therapy for Stage IV Renal Cell Carcinoma
Ipilimumab, Nivolumab, and Ciforadenant as First-Line Therapy for Stage IV Renal Cell Carcinoma
This phase 1b/2 trial tests the safety, side effects, and best dose of ciforadenant in combination with ipilimumab and nivolumab as initial (first-line) therapy for patients with stage IV renal cell carcinoma. Ciforadenant may stimulate the immune system in different ways and stop tumor cells from growing. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ciforadenant in combination with ipilimumab and nivolumab may help control the disease.
Kidney (Renal Cell),
Phase I
Phase I/II
Adults
Mol. targeted/Immunotherapy/Biologics
Not Available
Beckermann, Kathryn
National
Vanderbilt University
11-16-2023
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
Willing and able to provide a signed and dated written informed consent
Male or female >= 18 years of age
Confirmed diagnosis of clear cell RCC
Stage IV metastatic renal cell carcinoma per American Joint Committee on Cancer
No prior systemic therapy for advanced RCC
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * A tumor lesion situated in a previously irradiated area is considered a measurable/target lesion only if subsequent disease progression has been documented in the lesion
Has submitted an archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed paraffin-embedded tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue but not necessary. Details pertaining to tumor tissue submission can be found in the lab procedures manual
Willing and able to undergo bone and brain scans at baseline and continue to have scans performed if positive at screening
White blood cell (WBC) >= 2,000 /uL (within 21 days prior to first dose of protocol-indicated treatment)
Absolute neutrophil count (ANC) >= 1,500/uL (within 21 days prior to first dose of protocol-indicated treatment)
Platelets >= 100,000/uL (within 21 days prior to first dose of protocol-indicated treatment)
Hemoglobin (Hgb) >= 9.0 g/dl without requirement for transfusion in prior 4 weeks (within 21 days prior to first dose of protocol-indicated treatment)
Serum creatinine = 2 times institutional upper limit of normal (ULN), or calculated creatinine clearance >= 40 mL/min (per the Cockcroft-Gault formula) (within 21 days prior to first dose of protocol-indicated treatment)
Total bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who must have total bilirubin 3.0 mg/dL) (within 21 days prior to first dose of protocol-indicated treatment)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN (within 21 days prior to first dose of protocol-indicated treatment)
Women must not be breastfeeding while taking the study drug and for up to five months after the last dose of study drug
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to receiving first dose of protocol-indicated treatment * WOCBP is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal * Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes * If menopausal status is considered for the purpose of evaluating childbearing potential, women 62 years of age must have a documented serum follicle stimulating hormone (FSH) level within laboratory reference range for postmenopausal women, in order to be considered postmenopausal and not of childbearing potential
Women of childbearing potential (WOCBP) must agree to follow instructions for acceptable contraception from the time of signing consent, and for 23 weeks after their last dose of protocol-indicated treatment
Men not azoospermic who are sexually active with WOCBP must agree to follow instructions for acceptable contraception, from the time of signing consent, and for 31 weeks after their last dose of protocol-indicated treatment
Exclusion Criteria:
Prior systemic treatment including neoadjuvant or adjuvant therapy 6 months from protocol initiation is not allowed including an immune checkpoint inhibitor or tyrosine kinase inhibitors (TKI)
= 28 days before first dose of protocol-indicated treatment: * Major surgery requiring general anesthesia * Suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
= 14 days before first dose of protocol-indicated treatment: * Radiosurgery or radiotherapy * Minor surgery. (Note: Placement of a vascular access device is not considered minor or major surgery) * Active infection requiring infusion treatment
Known or suspected clinically significant active bleeding including active hemoptysis
Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disorder that could significantly affect the absorption of oral study drug e.g. Crohns disease, ulcerative colitis, chronic diarrhea (defined as > 4 loose stools per day), malabsorption, or bowel obstruction
Central nervous system (CNS) metastasis, unless asymptomatic and stable with imaging of the head by MRI unless contraindicated for the patient in which case CT is acceptable showing no change in CNS disease status for at least two (2) weeks prior to initiating protocol-indicated treatment
Any condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone or equivalent daily) or other immunosuppressive medications within 14 days prior to initiating protocol-indicated treatment * In the absence of active autoimmune disease: Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intra-articular, intranasal, and inhalational) = 10 mg/day prednisone or equivalent daily; and physiologic replacement doses of systemic corticosteroids = 10 mg/day prednisone or equivalent daily (e.g. hormone replacement therapy needed in patients with hypophysitis)
Active, known or suspected autoimmune disease * Subjects with type I diabetes mellitus; hypothyroidism only requiring hormone replacement; skin disorders such as vitiligo, psoriasis or alopecia not requiring systemic treatment; or conditions not expected by the investigator to recur in the absence of an external trigger are permitted to enroll
Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the investigator to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with and interpretation of scheduled visits, treatment schedule, laboratory tests and other study requirements
Willing and able to provide a signed and dated written informed consent
Male or female >= 18 years of age
Confirmed diagnosis of clear cell RCC
Stage IV metastatic renal cell carcinoma per American Joint Committee on Cancer
No prior systemic therapy for advanced RCC
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * A tumor lesion situated in a previously irradiated area is considered a measurable/target lesion only if subsequent disease progression has been documented in the lesion
Has submitted an archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed paraffin-embedded tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue but not necessary. Details pertaining to tumor tissue submission can be found in the lab procedures manual
Willing and able to undergo bone and brain scans at baseline and continue to have scans performed if positive at screening
White blood cell (WBC) >= 2,000 /uL (within 21 days prior to first dose of protocol-indicated treatment)
Absolute neutrophil count (ANC) >= 1,500/uL (within 21 days prior to first dose of protocol-indicated treatment)
Platelets >= 100,000/uL (within 21 days prior to first dose of protocol-indicated treatment)
Hemoglobin (Hgb) >= 9.0 g/dl without requirement for transfusion in prior 4 weeks (within 21 days prior to first dose of protocol-indicated treatment)
Serum creatinine = 2 times institutional upper limit of normal (ULN), or calculated creatinine clearance >= 40 mL/min (per the Cockcroft-Gault formula) (within 21 days prior to first dose of protocol-indicated treatment)
Total bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who must have total bilirubin 3.0 mg/dL) (within 21 days prior to first dose of protocol-indicated treatment)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN (within 21 days prior to first dose of protocol-indicated treatment)
Women must not be breastfeeding while taking the study drug and for up to five months after the last dose of study drug
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to receiving first dose of protocol-indicated treatment * WOCBP is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal * Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes * If menopausal status is considered for the purpose of evaluating childbearing potential, women 62 years of age must have a documented serum follicle stimulating hormone (FSH) level within laboratory reference range for postmenopausal women, in order to be considered postmenopausal and not of childbearing potential
Women of childbearing potential (WOCBP) must agree to follow instructions for acceptable contraception from the time of signing consent, and for 23 weeks after their last dose of protocol-indicated treatment
Men not azoospermic who are sexually active with WOCBP must agree to follow instructions for acceptable contraception, from the time of signing consent, and for 31 weeks after their last dose of protocol-indicated treatment
Exclusion Criteria:
Prior systemic treatment including neoadjuvant or adjuvant therapy 6 months from protocol initiation is not allowed including an immune checkpoint inhibitor or tyrosine kinase inhibitors (TKI)
= 28 days before first dose of protocol-indicated treatment: * Major surgery requiring general anesthesia * Suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
= 14 days before first dose of protocol-indicated treatment: * Radiosurgery or radiotherapy * Minor surgery. (Note: Placement of a vascular access device is not considered minor or major surgery) * Active infection requiring infusion treatment
Known or suspected clinically significant active bleeding including active hemoptysis
Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disorder that could significantly affect the absorption of oral study drug e.g. Crohns disease, ulcerative colitis, chronic diarrhea (defined as > 4 loose stools per day), malabsorption, or bowel obstruction
Central nervous system (CNS) metastasis, unless asymptomatic and stable with imaging of the head by MRI unless contraindicated for the patient in which case CT is acceptable showing no change in CNS disease status for at least two (2) weeks prior to initiating protocol-indicated treatment
Any condition requiring systemic treatment with either corticosteroids (> 10 mg/day prednisone or equivalent daily) or other immunosuppressive medications within 14 days prior to initiating protocol-indicated treatment * In the absence of active autoimmune disease: Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g. topical, ocular, intra-articular, intranasal, and inhalational) = 10 mg/day prednisone or equivalent daily; and physiologic replacement doses of systemic corticosteroids = 10 mg/day prednisone or equivalent daily (e.g. hormone replacement therapy needed in patients with hypophysitis)
Active, known or suspected autoimmune disease * Subjects with type I diabetes mellitus; hypothyroidism only requiring hormone replacement; skin disorders such as vitiligo, psoriasis or alopecia not requiring systemic treatment; or conditions not expected by the investigator to recur in the absence of an external trigger are permitted to enroll
Known psychiatric condition, social circumstance, or other medical condition reasonably judged by the investigator to unacceptably increase the risk of study participation; or to prohibit the understanding or rendering of informed consent or anticipated compliance with and interpretation of scheduled visits, treatment schedule, laboratory tests and other study requirements
