Trial Title:
Prime-boost Immunotherapeutic Trial in Men With Biochemical Recurrence After Definitive Local Therapy for Prostate Cancer
NCT ID:
NCT05617040
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Recurrence
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Phase 1 will follow a 3+3 design and determine the RP2R (dose level of both ChAdOx1-PCAQ
and MVA-PCAQ, and route of administration of MVA-PCAQ) that will be used in Phase 2.
Phase 2 will consist of 2 sequential stages. Stage 1 will enroll 19 additional
participants at the RP2R. If 4 or more participants treated at the RP2R have a PSA
response, Stage 2 will be opened to enrolment of up to 100 additional participants.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
ChAdOx1-PCAQ
Description:
Recombinant nonreplicating chimpanzee adenovirus Oxford 1 (ChAdOx1) vector encoding 4
prostate cancer antigens: prostate-specific antigen (PSA), prostatic acid phosphatase
(PAP), six-transmembrane epithelial antigen of prostate 1 (STEAP1), and an oncofoetal
antigen (5T4).
Intervention type:
Biological
Intervention name:
MVA-PCAQ
Description:
Replication-deficient recombinant Modified Vaccinia virus Ankara (MVA) vector encoding
the same prostate cancer antigens as ChAdOx1-PCAQ (prostate-specific antigen (PSA),
prostatic acid phosphatase (PAP), six-transmembrane epithelial antigen of prostate 1
(STEAP1), and an oncofoetal antigen (5T4))
Summary:
This is a multi-centre, Phase 1/2, open-label clinical trial of the VTP-850 prime-boost
immunotherapeutic in men with biochemical recurrence after definitive local therapy for
prostate cancer.
Detailed description:
This is a multi-center Phase 1/2 clinical trial to evaluate safety, PSA response, and
immunogenicity of the VTP850 prime-boost immunotherapeutic in men with biochemical
recurrence of prostate cancer (PCa) after definitive local therapy for PCa.
VTP-850 consists of 2 components: ChAdOx1-PCAQ and MVA-PCAQ. All participants will
receive ChAdOx1-PCAQ on Day 1 (prime) and MVA-PCAQ on Days 29 and 57 (boosts;
Intervention Period). Participants will be followed for 6 months or until start of new
therapy such as Androgen Deprivation Therapy (ADT) or until development of unequivocal
metastatic PCa (Short-term Follow-up Period). Participants who have a prostate-specific
antigen (PSA) response, defined as ≥50% reduction in serum PSA compared to baseline at
any time, measured twice consecutively, at least 2 weeks apart, during the 6 months
follow up will be followed for an additional 18 months, up to 24 months from first dose,
or until start of new therapy such as ADT or development of unequivocal metastatic PCa
(Long-term Follow-up Period).
Phase 1 (15-18 participants) will follow a 3+3 design to determine the recommended phase
2 regimen (RP2R; dose level of both ChAdOx1-PCAQ and MVA-PCAQ, and route of
administration of MVA-PCAQ (IM or IV)) that will be used in Phase 2.
Phase 2 will consist of 2 sequential stages. In Stage 1 of Phase 2, 19 additional
participants will be enrolled at the chosen Phase 2 regimen. If 4 or more of the 25
participants at the RP2R (including the Phase 1 participants who received the same dose
regimen) have a PSA response, Stage 2 will be opened to enrolment of up to 100 additional
participants.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Males aged 18 years and above at the time of signing the informed consent.
2. Histologically or cytologically confirmed adenocarcinoma of the prostate.
3. Has undergone primary therapy for prostate cancer (radical prostatectomy and/or
definitive external beam radiation and/or brachytherapy). Salvage external radiation
therapy (XRT) following radical prostatectomy >6 months prior to Day 1 is allowed.
4. No further local therapy to prostate or systemic therapy for prostate cancer and no
metastasis-directed therapy for PSA positron emission tomography (PET) positive
lesions planned within 4 months after the first dose of VTP-850.
5. Serum testosterone >175 ng/dL.
6. Nonmetastatic (M0) disease and no evidence of prostatic bed recurrence verified by
whole body bone scintigraphy and either CT or MRI. Note that a positive PSMA PET
does not exclude the participant if the conventional scans are negative.
7. Serum PSA of >0.3 ng/mL for participants with prior radical prostatectomy (with or
without salvage radiotherapy), or serum PSA of 2 ng/mL above nadir for participants
with prior external beam radiation or brachytherapy.
8. PSA doubling time ≤12 months.
9. Not planning to start ADT for at least 4 months after Day 1.
10. Eastern Cooperative Oncology Group (ECOG) Score 0 or 1.
11. Baseline laboratory parameters must meet the following criteria:
- Haemoglobin ≥110 g/L
- White cell count ≥2.0×10^9/L
- Absolute neutrophil count ≥1.5×10^9/L
- Lymphocytes ≥0.9×10^9/L
- Platelets ≥100×10^9/L
- Creatinine ≤1.5×upper limit of normal (ULN) OR calculated creatinine clearance
≥50 mL/min by the Cockcroft Gault formula
- Total bilirubin ≤1.5×ULN, (total bilirubin >1.5×ULN is acceptable if total
bilirubin is fractionated and direct bilirubin <35%)
- Alanine aminotransferase ≤1.5×ULN
- Aspartate aminotransferase ≤1.5×ULN
- Troponin T within normal range
- HbA1c <7 %
12. Agrees to the following during the trial for at least 65 days after the last dose of
VTP-850:
- Refrain from donating sperm PLUS, either
- Be abstinent from heterosexual intercourse as their preferred and usual
lifestyle (abstinent on a long-term and persistent basis) and agree to remain
abstinent OR
- Agrees to use a male condom when having sexual intercourse with a woman of
childbearing potential, and should also be advised of the benefit for a female
partner to use a highly effective method of contraception as a condom may break
or leak.
13. Agrees to comply with all scheduled visits, VTP-850 administration plan, laboratory
tests, lifestyle considerations and other trial procedures
Exclusion Criteria:
1. Any other prior malignancy within the past 5 years except for basal cell or squamous
epithelial carcinomas of the skin that have been resected with no evidence of
metastatic disease for 3 years.
2. Unstable medical condition, drug or alcohol abuse, or medical or psychiatric
condition that in the opinion of the investigator would affect the safety of the
participant or the evaluation of the data or interfere with adherence to the trial
requirements.
3. Significant history of or current cardiovascular, respiratory, renal,
gastrointestinal, endocrinological, haematological or neurological disorders
constituting a risk when taking the trial intervention or interfering with the
interpretation of data; cardiac event or heart failure in the previous 6 months.
4. Current or chronic history of liver disease. This includes but is not limited to:
hepatitis virus infections, cirrhosis, drug- or alcohol-related liver disease, non
alcoholic steatohepatitis, autoimmune hepatitis, hemochromatosis, Wilson's disease,
α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing
cholangitis or any other liver disease considered clinically significant by the
investigator. (Note that history of hepatitis C infection, Gilbert's syndrome or non
alcoholic fatty liver not associated with steatohepatitis are not exclusions. In
line with Exclusion Criterion 10, active hepatitis C infection is exclusionary.)
5. Active autoimmune disease that has required systemic treatment in past 2 years with
use of disease modifying agents, chronic corticosteroids (>14 days) or
immunosuppressive drugs. Hormone replacement therapy (e.g., thyroxine, insulin or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is allowed.
6. History of severe allergy to eggs or history of severe reaction to any previous
vaccination that required medical attention.
7. Medical history that could increase the participant's risk of reaction to a vaccine,
including but not limited to capillary leak syndrome, transverse myelitis, multiple
sclerosis, Guillain Barré syndrome, significant thrombocytopenia, thrombosis with
thrombocytopenia syndrome (also termed vaccine-induced thrombotic thrombocytopenia),
heparin-induced thrombocytopenia, or hereditary angioedema, acquired angioedema or
idiopathic angioedema.
8. Any immunocompromised state, or history of solid organ or stem cell transplantation.
9. Active infection requiring parenteral antibiotic therapy or causing fever
(temperature ≥38.0˚C) within 7 days prior to Day 1, or unexplained fever
(temperature ≥38.0˚C) within 7 days prior to Day 1.
10. Known history of infection with hepatitis B virus, or human immunodeficiency virus,
or active hepatitis C virus infection (antibody and RNA positive).
11. Received XRT following radical prostatectomy within 6 months prior to Day 1.
12. Received ADT outside of the initial primary therapy
13. Prior chemotherapy or immunotherapy (including vaccines or checkpoint inhibitors) or
experimental agent or participation in a clinical trial for prostate cancer with the
exception of those taking part as primary treatment option.
14. Received a vaccine with adenovirus vector within 3 months prior to Day 1.
15. Received any live vaccine within 30 days prior to Day 1, or planned vaccination to
occur within 3 months after Day 1.
16. Received any non-live/inactivated vaccine within 14 days of Day 1 or planned
non-live vaccination to occur within 10 weeks after Day 1.
17. Administration of immunoglobulins and/or any blood products within 28 days prior to
Day 1.
18. Condition requiring systemic treatment with corticosteroids or other
immunosuppressive medications within 14 days of first dose of VTP-850. Note that
adrenal replacement doses are permitted. Inhaled and topical corticosteroids are
allowed.
19. Received an investigational product or investigational surgical procedure in the 3
months prior to Day 1 or planned use during the trial period, or participation at
any time in clinical trial for prostate cancer with exception of those taking part
as primary treatment.
20. Any significant cardiovascular conditions per the investigator within 6 months
before study entry including but not limited to: myocardial infarction, stroke, New
York Heart Association class III or IV heart failure, thromboembolic events, major
cardiovascular or cerebrovascular procedures, history of cardiac valvular disease or
other structural heart disease or any other condition that in the investigator's
opinion puts the participant at unacceptable risk to enter the study.
21. Participant with QT interval corrected for heart rate (QTc) determined using
Fridericia's formula (QTcF; QTcF = QT/[R-R interval {RR}^0.33]) > 470 msec and any
other ECG findings deemed clinically significant at screening.
22. Uncontrolled hypertension that, in the opinion of the Investigator, puts participant
at increased risk of a cardiovascular event at the time of screening.
23. Uncontrolled dyslipidemia that, in the opinion of the Investigator, puts participant
at increased risk of cardiovascular event at the time of screening.
Gender:
Male
Gender based:
Yes
Gender description:
Male participants only
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Facility:
Name:
Columbia University Irving Medical Center
Address:
City:
New York
Zip:
10032
Country:
United States
Facility:
Name:
Cornell University
Address:
City:
New York
Zip:
10065-4805
Country:
United States
Facility:
Name:
Fox Chase Cancer Center
Address:
City:
Philadelphia
Zip:
19111
Country:
United States
Facility:
Name:
Carolina Urologic Research Center
Address:
City:
Myrtle Beach
Zip:
29572
Country:
United States
Facility:
Name:
University of Virginia Health System
Address:
City:
Charlottesville
Zip:
22908
Country:
United States
Facility:
Name:
Fred Hutchinson Cancer Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Start date:
January 30, 2023
Completion date:
April 2027
Lead sponsor:
Agency:
Barinthus Biotherapeutics
Agency class:
Industry
Source:
Barinthus Biotherapeutics
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05617040
