RECRUITING

Adenosine Signaling Modulation and Immune Checkpoint Inhibition With Hormone Sensitive Oligometastatic Prostate Cancer

Conditions

Oligometastatic Prostate Cancer Adenosine Signaling AB680 AB928 AB122 Quemliclustatm Etrumadenant Zimberelimab

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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 study will evaluate the safety and effectiveness of a combination of study drugs including zimberelimab, etrumadenant, and quemliclustat in combination with metastasis-directed irradiation in men with hormone sensitive oligometastatic prostate cancer. The study aims to test the hypothesis that targeted inhibition of the adenosine signaling axis (quemliclustat (CD73 antagonist) + etrumadenant (A2AR/A2BR antagonist)) and immune checkpoint inhibition (zimberelimab, α-PD-1) in combination with metastasis-directed stereotactic body radiation therapy (SBRT) will improve local control, progression-free survival (PFS), and hormone therapy-free survival and mitigate immunosuppressive changes to the tumor microenvironment (TME), compared to SBRT alone.

Official Title

Phase II Single Arm Study Testing SBRT, Adenosine Signaling Modulation (AB680, AB928), and Immune Checkpoint Inhibition (AB122) for Men With Hormone Sensitive Oligometastatic Prostate Cancer

Quick Facts

Study Start:2023-07-01

Study Completion:2028-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05915442

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 to 99 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Patient must have histologically confirmed adenocarcinoma of the prostate. 2. Patient's primary prostate cancer tumor treated with surgery and/or radiation (+/- ADT). 3. Patients must have one to three asymptomatic metastatic tumors of the bone or soft tissue that developed in the preceding 6 months that are \< 5cm or \< 250 cm3. 4. Prostate-specific antigen (PSA) \> 0.5 ng/mL but \< 50ng/ml 5. PSA doubling time (PSADT) \< 15 months (using all available PSA values from time of relapse) 6. Testosterone \> 125 ng/mL 7. Age ≥18 years. 8. Patient must have life expectancy \> 12 months. 9. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 10. Normal organ and marrow function as defined below: * leukocytes ≥3,000/mcL * absolute neutrophil count ≥1,500/mcL * platelets ≥100,000/mcL * total bilirubin within normal institutional limits * aspartate transaminase (AST)(serum glutamic-oxaloacetic transaminase (SGOT))/alanine transaminase (ALT)(serum glutamic-pyruvic transaminase (SGPT) ) ≤2.5 × institutional upper limit of normal creatinine, within normal institutional limits 11. Male participants with female partners of childbearing potential are required to use highly effective contraceptive measures which include condom use. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. A female partner of is considered a woman of childbearing potential (WOCBP) following menarche and until becoming postmenopausal unless permanently sterile. * Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. * A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. * Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal * Progestogen only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable * Intrauterine device * Intrauterine hormone-releasing system * Surgical sterilization * The male participant is vasectomized (with documented medical confirmation of surgical success) and is the sole sexual partner of the WOCBP participant * Female partner of the male participant has undergone bilateral tubal ligation * Complete sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. 12. Male participants should refrain from donating sperm for 180 days after the last dose of the study drugs. 13. Patient must have the ability to understand and the willingness to sign written informed consent.	1. Patient may not have had prior systemic therapy, with the exception of androgen deprivation therapy (ADT) associated with treatment of the primary prostate tumor or with salvage radiation therapy. The ADT could not exceed 3-years in duration and must have occurred greater than 6 months before time of enrollment. 2. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. 3. Spinal cord compression or impending spinal cord compression. 4. Pulmonary and/or liver metastases \> 1.0cm in largest dimension. 5. History of malignancy other than prostate cancer within 2 years prior to screening, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as nonmelanoma skin carcinoma or ductal carcinoma in situ. 6. Use of other investigational agents or treatment protocol. 7. Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment with the exception of patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study. 8. Inability to swallow medications. 9. Malabsorption condition that would alter the absorption of orally administered medications. 10. Grade ≥ 3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment. 11. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. 12. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. 13. Positive total hepatitis B core antibody (HBcAb) test at screening. Patients can be eligible if positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV test will be performed only for participants who have a positive total HBcAb test. Due to safety concerns related to viral activation, development of a secondary malignancy, as well as the potential for increased treatment-related toxicity, eligible participants must not have evidence of chronic viral infection at screening. 14. Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had: 1. Oral treatment with strong inhibitors of breast cancer resistance protein (BCRP) (e.g., cyclosporin A, eltrombopag) or BRCP substrates with a narrow therapeutic window, administered orally (e.g., prazosin, rosuvastatin) within 4 weeks or 5 drug-elimination half-lives of the drug (whichever is longer) prior to initiation of study treatment. 2. Oral treatment with strong inhibitors of P-glycoprotein (P-gp) substrates (e.g., itraconazole, quinidine, verapamil, dronedarone, ranolazine) or P-gp with a narrow therapeutic window, administered orally (e.g., digoxin) within 4 weeks or 5 drug-elimination half-lives of the drug (whichever is longer) prior to initiation of study treatment. 3. Treatment with known strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) or strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment. 4. Treatment with known strong UDP-glucuronosyltransferases (UGTs) of UGT1A1, 1A4, 1A9 and 2B4 inhibitors (e.g., atazanavir) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment. 5. Treatment with known sensitive substrates of BSEP within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment. 6. Treatment with known sensitive substrates of OCT2 within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment. 7. Treatment with known sensitive substrates of MATE1 within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment. 15. Immunosuppression (e.g., solid organ transplant on immunosuppression). 16. No known HIV, or active with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV). 17. Active autoimmune disease. 18. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 19. Inability to lie flat to tolerate computed tomography (CT) simulation study and oligometastasis-directed stereotactic body radiotherapy (SBRT). 20. Use of any live vaccines against infectious diseases within 28 days of first dose of investigational products. 21. Refusal to sign informed consent.

Inclusion Criteria

Exclusion Criteria

1. Patient must have histologically confirmed adenocarcinoma of the prostate.
2. Patient's primary prostate cancer tumor treated with surgery and/or radiation (+/- ADT).
3. Patients must have one to three asymptomatic metastatic tumors of the bone or soft tissue that developed in the preceding 6 months that are \< 5cm or \< 250 cm3.
4. Prostate-specific antigen (PSA) \> 0.5 ng/mL but \< 50ng/ml
5. PSA doubling time (PSADT) \< 15 months (using all available PSA values from time of relapse)
6. Testosterone \> 125 ng/mL
7. Age ≥18 years.
8. Patient must have life expectancy \> 12 months.
9. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
10. Normal organ and marrow function as defined below:
* leukocytes ≥3,000/mcL
* absolute neutrophil count ≥1,500/mcL
* platelets ≥100,000/mcL
* total bilirubin within normal institutional limits
* aspartate transaminase (AST)(serum glutamic-oxaloacetic transaminase (SGOT))/alanine transaminase (ALT)(serum glutamic-pyruvic transaminase (SGPT) ) ≤2.5 × institutional upper limit of normal creatinine, within normal institutional limits
11. Male participants with female partners of childbearing potential are required to use highly effective contraceptive measures which include condom use. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. A female partner of is considered a woman of childbearing potential (WOCBP) following menarche and until becoming postmenopausal unless permanently sterile.
* Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
* A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
* Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
* Progestogen only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
* Intrauterine device
* Intrauterine hormone-releasing system
* Surgical sterilization
* The male participant is vasectomized (with documented medical confirmation of surgical success) and is the sole sexual partner of the WOCBP participant
* Female partner of the male participant has undergone bilateral tubal ligation
* Complete sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant.
12. Male participants should refrain from donating sperm for 180 days after the last dose of the study drugs.
13. Patient must have the ability to understand and the willingness to sign written informed consent.

1. Patient may not have had prior systemic therapy, with the exception of androgen deprivation therapy (ADT) associated with treatment of the primary prostate tumor or with salvage radiation therapy. The ADT could not exceed 3-years in duration and must have occurred greater than 6 months before time of enrollment.
2. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
3. Spinal cord compression or impending spinal cord compression.
4. Pulmonary and/or liver metastases \> 1.0cm in largest dimension.
5. History of malignancy other than prostate cancer within 2 years prior to screening, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as nonmelanoma skin carcinoma or ductal carcinoma in situ.
6. Use of other investigational agents or treatment protocol.
7. Treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment with the exception of patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
8. Inability to swallow medications.
9. Malabsorption condition that would alter the absorption of orally administered medications.
10. Grade ≥ 3 hemorrhage or bleeding event within 28 days prior to initiation of study treatment.
11. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
12. Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
13. Positive total hepatitis B core antibody (HBcAb) test at screening. Patients can be eligible if positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV test will be performed only for participants who have a positive total HBcAb test. Due to safety concerns related to viral activation, development of a secondary malignancy, as well as the potential for increased treatment-related toxicity, eligible participants must not have evidence of chronic viral infection at screening.
14. Due to the potential risk for drug-drug interactions with etrumadenant, participants must not have had:
1. Oral treatment with strong inhibitors of breast cancer resistance protein (BCRP) (e.g., cyclosporin A, eltrombopag) or BRCP substrates with a narrow therapeutic window, administered orally (e.g., prazosin, rosuvastatin) within 4 weeks or 5 drug-elimination half-lives of the drug (whichever is longer) prior to initiation of study treatment.
2. Oral treatment with strong inhibitors of P-glycoprotein (P-gp) substrates (e.g., itraconazole, quinidine, verapamil, dronedarone, ranolazine) or P-gp with a narrow therapeutic window, administered orally (e.g., digoxin) within 4 weeks or 5 drug-elimination half-lives of the drug (whichever is longer) prior to initiation of study treatment.
3. Treatment with known strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) or strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
4. Treatment with known strong UDP-glucuronosyltransferases (UGTs) of UGT1A1, 1A4, 1A9 and 2B4 inhibitors (e.g., atazanavir) within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment.
5. Treatment with known sensitive substrates of BSEP within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment.
6. Treatment with known sensitive substrates of OCT2 within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment.
7. Treatment with known sensitive substrates of MATE1 within 4 weeks or 5 half-lives of the drug, whichever is longer, prior to the initiation of study treatment.
15. Immunosuppression (e.g., solid organ transplant on immunosuppression).
16. No known HIV, or active with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV).
17. Active autoimmune disease.
18. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
19. Inability to lie flat to tolerate computed tomography (CT) simulation study and oligometastasis-directed stereotactic body radiotherapy (SBRT).
20. Use of any live vaccines against infectious diseases within 28 days of first dose of investigational products.
21. Refusal to sign informed consent.

Contacts and Locations

Study Contact

Catherine S. Spina, MD, PhD

CONTACT

212-305-7406

css2190@cumc.columbia.edu

Research Nurse Navigator

CONTACT

212-342-5162

cancerclinicaltrials@cumc.columbia.edu

Principal Investigator

Catherine S. Spina, MD, PhD

PRINCIPAL_INVESTIGATOR

Columbia University

Study Locations (Sites)

Columbia University Irving Medical Center / NewYork-Presbyterian Hospital

New York, New York, 10032

United States

Collaborators and Investigators

Sponsor: Catherine Spina

Catherine S. Spina, MD, PhD, PRINCIPAL_INVESTIGATOR, Columbia University

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 Date2023-07-01

Study Completion Date2028-12

Study Record Updates

Study Start Date2023-07-01

Study Completion Date2028-12

Terms related to this study

Keywords Provided by Researchers

Adenosine Signaling
AB680
AB928
AB122
Quemliclustatm
Etrumadenant
Zimberelimab

Additional Relevant MeSH Terms

Oligometastatic Prostate Cancer