Trial Title:
Adenosine Signaling Modulation and Immune Checkpoint Inhibition With Hormone Sensitive Oligometastatic Prostate Cancer
NCT ID:
NCT05915442
Condition:
Oligometastatic Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Quemliclustat
Conditions: Keywords:
Adenosine Signaling
AB680
AB928
AB122
Quemliclustatm
Etrumadenant
Zimberelimab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
Simon Two-Stage design: In the first stage, trial will enroll 14 patients. If two or more
patients show progression at 6 months, the study is terminated at the end of stage I.
However, if 13 of the 14 remain free from progressive disease at 6 months, then the study
would move onto the second stage. In this stage, n=9 additional patients will be
enrolled, for a total of 23 total. If 21 of the 23 patients remain progression-free at 6
months, then the null hypothesis is rejected, and we will consider the addition of
quemliclustat, etrumadenant, and zimberelimab to SBRT worthy of further study.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Quemliclustat
Description:
100mg IV once every two weeks
Arm group label:
Treatment with quemliclustatm, etrumadenant, zimberelimab and SBRT
Other name:
AB680
Intervention type:
Drug
Intervention name:
Etrumadenant
Description:
150 mg orally (PO) once a day (QD)
Arm group label:
Treatment with quemliclustatm, etrumadenant, zimberelimab and SBRT
Other name:
AB928
Intervention type:
Drug
Intervention name:
Zimberelimab
Description:
240 mg IV once every two weeks starting within 1 week of completing metastasis-directed
SBRT
Arm group label:
Treatment with quemliclustatm, etrumadenant, zimberelimab and SBRT
Other name:
AB122
Intervention type:
Radiation
Intervention name:
Stereotactic Body Radiation Therapy
Description:
Standard of care metastasis-directed hypofractionated radiotherapy treatment starting 4
weeks (+/- 1 week) of starting Etrumadenant and Quemliclustat
Arm group label:
Treatment with quemliclustatm, etrumadenant, zimberelimab and SBRT
Other name:
SBRT
Summary:
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.
Detailed description:
The optimal therapeutic approach to men with oligometastatic (1-3 or 1-5 sites of
metastatic disease) prostate cancer is ever more important as advanced imaging
technologies are becoming standard of care, providing clinicians with the tools to
accurately diagnose and localize oligometastatic prostate cancer. Hence, methods to
improve the local curative potential of stereotactic body radiation therapy (SBRT) is a
timely and important opportunity. In addition, previous data suggest that the adenosine
A2A pathway may be a particularly attractive avenue for intervention in the context of
radiation, thus influencing multiple suppressive populations within the tumor
microenvironment (TME).
Immunotherapy based on the PD-1/PD-L1 signaling axis is a mainstay of therapy across
multiple types of malignancies. This study aims to evaluate the effectiveness of a PD-1
inhibitor (zimberelimab) in combination with a selective dual antagonist of A2aR and A2bR
(etrumadenant) and an anti-CD73 (quemliclustat). Immune checkpoint inhibitors and
targeted inhibitors of the adenosine signaling axis modulate the TME and aspects of the
systemic immune system to overcome tumor-induced immune suppression and improve responses
to therapy.
This study aims to determine the effect of etrumadenant, quemliclustat and zimberelimab
[experimental] when given with ablative radiation (SBRT)[standard of care] on the
oligoprogressive disease (hormone sensitive oligometastatic prostate cancer), defined by
being free from radiographic progression of irradiated target metastases and PSA
(prostate surface antigen) response at 6 months. PSA response, local control,
progression-free survival (PFS), treatment response, ADT-free survival, time-to-pain, and
safety and tolerability will also be measured. By employing a Simon Two-Stage design, the
trial will test whether or not etrumadenant + quemliclustat and zimberelimab combined
with ablative radiation (SBRT) will improve PFS compared to SBRT alone (ORIOLE).
Criteria for eligibility:
Criteria:
Inclusion 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.
Highly effective contraceptive measures include:
- 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.
Exclusion Criteria:
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.
Gender:
Male
Minimum age:
18 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Columbia University Irving Medical Center / NewYork-Presbyterian Hospital
Address:
City:
New York
Zip:
10032
Country:
United States
Status:
Recruiting
Contact:
Last name:
Research Nurse Navigator
Phone:
212-342-5162
Email:
cancerclinicaltrials@cumc.columbia.edu
Investigator:
Last name:
Catherine S. Spina, MD, PhD
Email:
Principal Investigator
Start date:
July 1, 2023
Completion date:
December 2028
Lead sponsor:
Agency:
Catherine Spina
Agency class:
Other
Collaborator:
Agency:
Arcus Biosciences, Inc.
Agency class:
Industry
Source:
Columbia University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05915442
