Back to results

Vaccination in Prostate Cancer (VANCE)

Primary Purpose

Prostate Cancer

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

ChAdOx1.5T4

MVA.5T4

Cyclophosphamide

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria(Radical Prostatectomy patients):

Males aged 18 years and older
Histologically confirmed prostate cancer diagnosed on biopsy within 6 months
Clinically localised, low or intermediate risk prostate cancer, i.e.:
- Gleason score ≤ 7
- Local tumour stage ≤T2c
- No evidence of metastases (Nx/N0 and Mx/M0)
- PSA ≤ 20 ng/ml
Scheduled for and considered fit for radical prostatectomy
Absence of any indication to perform urgent surgery that would not allow administration of the vaccine during the 12 week period prior to radical prostatectomy
No invasive treatment for prostatic disease within the last 2 years
Subject is free of clinically apparent/active autoimmune disease (no prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave's Disease, Hashimoto's Thyroiditis, Multiple Sclerosis, and Insulin Dependent Diabetes Mellitus). Note subjects with Non-Insulin Dependent Diabetes Mellitus can be included.
Subject has adequate bone marrow function as defined by an Absolute Lymphocyte Count (ALC) ≥ 500/µL, Absolute Neutrophil Count (ANC) >1200/µL, Platelet Count >100,000/µL.
Subject must practice a reliable form of contraception (barrier or vasectomy) while they are being treated with vaccines and another effective method of birth control must also be used by their partner

Inclusion Criteria (Active Surveillance patients)

Males aged 18 and older
Histologically confirmed prostate cancer diagnosed on biopsy within 6 months
Clinically localised, low or intermediate risk prostate cancer, i.e.:
- Gleason score ≤ 7
- Local tumour stage ≤T2c
- No evidence of metastases (Nx/N0 and Mx/M0)
- PSA ≤ 20 ng/ml
Stable disease on Active Surveillance for a minimum of 12 months previously
Suitable to remain on Active Surveillance at time of last clinical assessment
No invasive treatment for prostatic disease within the last 2 years
Subject is free of clinically apparent/active autoimmune disease (no prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave's Disease, Hashimoto's Thyroiditis, Multiple Sclerosis, and Insulin Dependent Diabetes Mellitus). Note subjects with Non-Insulin Dependent Diabetes Mellitus can be included.
Subject has adequate bone marrow function as defined by an Absolute Lymphocyte Count (ALC) ≥ 500/µL, Absolute Neutrophil Count (ANC) >1200/µL, Platelet Count >100,000/µL.
Subject must practice a reliable form of contraception (barrier or vasectomy) while they are being treated with vaccines and another effective method of birth control must also be used by their partner

Exclusion Criteria:

Diagnosis of any cancer other than prostate cancer within the last 5 years (except basal cell carcinoma)
Any suspicion of metastatic cancer
Any Gleason grade 5 component in the prostatic biopsies
Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period
Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
Seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) or HIV
Any confirmed or suspected immunosuppressive or immunodeficient state, asplenia, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled/topical steroids are allowed)
Platelet count >400,000/μL; Monocytes >80,000/μL; Hemoglobin <11g/dL
Known allergy to neomycin
History of allergic response to previous vaccinia vaccinations
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
History of hypersensitivity and haemorrhagic cystitis
Any history of anaphylaxis
Suspected or known current injecting drug or alcohol abuse (as defined by an alcohol intake of greater than 42 units per week)
History of a serious psychiatric condition or other circumstance s that may be associated with not understanding or complying with the study protocol

Sites / Locations

University of Oxford
Royal Hallamshire Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

CHAMVA standard regime

CHAMVA+CTX standard regime

MVA standard regime

MVA+CTX standard regime

CHAMVA accelerated regime

CHAMVA+CTX accelerated regime

CHAMVA accelerated regime AS

CHAMVA+CTX accelerated regime AS

Arm Description

ChAdOx1.5T4 prime followed by two boost of MVA.5T4 vaccine at 4 week intervals until radical prostatectomy

One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by two boost of MVA.5T4 at 4 week intervals until radical prostatectomy.

Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy

One week of low dose cyclophosphamide pre-conditioning before each vaccination.Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy

ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.

One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.

ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.

One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.

Outcomes

Primary Outcome Measures

Vaccine safety and immunogenicity

Development or increase in anti-5T4 cellular and humoral responses in patients treated with CHAMVA or CHAMVA + CTX

Secondary Outcome Measures

Cellular and humoral immune response with CHAMVA

Development or increase in anti-5T4 cellular and humoral responses in patients treated with the CHAMVA vaccination regimes

Cellular and humoral immune response with MVA

Development or increase in anti-5T4 cellular and humoral response in patients treated with the MVA vaccination regimes.

PSA level change secondary to vaccination

PSA level decrease in patients treated with CHAMVA or MVA vaccination at week 4,8 or 12.

MRI or Gleason score change secondary to vaccination

Reduction of tumour burden or Gleason score at weeks 4, 8 or 12.

Regulatory T-cell response

Change in the frequency of regulatory T-cells measured in blood or tumour samples from patients treated with metronomic cyclophosphamide compared to patients not receiving cyclophosphamide

Full Information

NCT ID

NCT02390063

First Posted

March 10, 2015

Last Updated

February 7, 2020

Sponsor

University of Oxford

1. Study Identification

Unique Protocol Identification Number

NCT02390063

Brief Title

Vaccination in Prostate Cancer (VANCE)

Official Title

A Randomized Phase I Study to Determine the Safety and Immunogenicity of ChAd-MVA Vaccination Compared to MVA Alone With and Without Low Dose Cyclophosphamide in Low and Intermediate Risk Localised Prostate Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

June 2015 (undefined)

Primary Completion Date

May 15, 2018 (Actual)

Study Completion Date

May 15, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Oxford

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a clinical trial of a new treatment for prostate cancer that is a type of vaccine that could be a new way to treat cancer. A vaccine that could alert the immune system to the presence of cancer cells in the body may enable the immune system to target and kill those cells effectively. This vaccine is intended to work by making the immune system kill cells that have a special protein (called 5T4) that is present on the surface of cancer cells. The vaccine is made up of two recombinant viruses ("ChAdOx1" and "MVA") that have been designed to produce the 5T4 protein and have been modified so that they are weakened and cannot reproduce themselves within the body like normal viruses. Once injected into the body, these viruses make the 5T4 protein and help the body's immune system to learn to target this protein and destroy cancer cells. This is a first-in-human study to evaluate the safety and immunogenicity of ChAdOx1.5T4-MVA.5T4 vaccination regime. It is evaluated in neo-adjuvant setting in low and intermediate risk localised prostate cancer patients who have either decided to have their prostate removed or are stable on active surveillance.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Factorial Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CHAMVA standard regime

Arm Type

Experimental

Arm Description

ChAdOx1.5T4 prime followed by two boost of MVA.5T4 vaccine at 4 week intervals until radical prostatectomy

Arm Title

CHAMVA+CTX standard regime

Arm Type

Experimental

Arm Description

One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by two boost of MVA.5T4 at 4 week intervals until radical prostatectomy.

Arm Title

MVA standard regime

Arm Type

Active Comparator

Arm Description

Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy

Arm Title

MVA+CTX standard regime

Arm Type

Active Comparator

Arm Description

One week of low dose cyclophosphamide pre-conditioning before each vaccination.Three MVA.5T4 vaccinations at 4 week intervals until radical prostatectomy

Arm Title

CHAMVA accelerated regime

Arm Type

Experimental

Arm Description

ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.

Arm Title

CHAMVA+CTX accelerated regime

Arm Type

Experimental

Arm Description

One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later until radical prostatectomy.

Arm Title

CHAMVA accelerated regime AS

Arm Type

Experimental

Arm Description

ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.

Arm Title

CHAMVA+CTX accelerated regime AS

Arm Type

Experimental

Arm Description

One week of low dose cyclophosphamide pre-conditioning before each vaccination. ChAdOx1.5T4 prime followed by one boost of MVA.5T4 one week later. Patients continue on active surveillance.

Intervention Type

Biological

Intervention Name(s)

ChAdOx1.5T4

Intervention Description

A recombinant simian adenovirus encoding human tumour-associated antigen 5T4

Intervention Type

Biological

Intervention Name(s)

MVA.5T4

Intervention Description

A recombinant replication deficient Modified Vaccinia Ankara virus encoding human tumour-associated antigen 5T4

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

CTX, CY, Cytoxan

Intervention Description

Metronomic cyclophosphamide (50mg bd)

Primary Outcome Measure Information:

Title

Vaccine safety and immunogenicity

Description

Development or increase in anti-5T4 cellular and humoral responses in patients treated with CHAMVA or CHAMVA + CTX

Time Frame

Up to 52 weeks

Secondary Outcome Measure Information:

Title

Cellular and humoral immune response with CHAMVA

Description

Development or increase in anti-5T4 cellular and humoral responses in patients treated with the CHAMVA vaccination regimes

Time Frame

Up to 52 weeks

Title

Cellular and humoral immune response with MVA

Description

Development or increase in anti-5T4 cellular and humoral response in patients treated with the MVA vaccination regimes.

Time Frame

Up to 52 weeks

Title

PSA level change secondary to vaccination

Description

PSA level decrease in patients treated with CHAMVA or MVA vaccination at week 4,8 or 12.

Time Frame

Participants will be followed for the duration of the study, up to 52 weeks

Title

MRI or Gleason score change secondary to vaccination

Description

Reduction of tumour burden or Gleason score at weeks 4, 8 or 12.

Time Frame

Participants will be followed for the duration of the study, up to 52 weeks

Title

Regulatory T-cell response

Description

Change in the frequency of regulatory T-cells measured in blood or tumour samples from patients treated with metronomic cyclophosphamide compared to patients not receiving cyclophosphamide

Time Frame

Participants will be followed for the duration of the study, up to 52 weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria(Radical Prostatectomy patients): Males aged 18 years and older Histologically confirmed prostate cancer diagnosed on biopsy within 6 months Clinically localised, low or intermediate risk prostate cancer, i.e.: Gleason score ≤ 7 Local tumour stage ≤T2c No evidence of metastases (Nx/N0 and Mx/M0) PSA ≤ 20 ng/ml Scheduled for and considered fit for radical prostatectomy Absence of any indication to perform urgent surgery that would not allow administration of the vaccine during the 12 week period prior to radical prostatectomy No invasive treatment for prostatic disease within the last 2 years Subject is free of clinically apparent/active autoimmune disease (no prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave's Disease, Hashimoto's Thyroiditis, Multiple Sclerosis, and Insulin Dependent Diabetes Mellitus). Note subjects with Non-Insulin Dependent Diabetes Mellitus can be included. Subject has adequate bone marrow function as defined by an Absolute Lymphocyte Count (ALC) ≥ 500/µL, Absolute Neutrophil Count (ANC) >1200/µL, Platelet Count >100,000/µL. Subject must practice a reliable form of contraception (barrier or vasectomy) while they are being treated with vaccines and another effective method of birth control must also be used by their partner Inclusion Criteria (Active Surveillance patients) Males aged 18 and older Histologically confirmed prostate cancer diagnosed on biopsy within 6 months Clinically localised, low or intermediate risk prostate cancer, i.e.: Gleason score ≤ 7 Local tumour stage ≤T2c No evidence of metastases (Nx/N0 and Mx/M0) PSA ≤ 20 ng/ml Stable disease on Active Surveillance for a minimum of 12 months previously Suitable to remain on Active Surveillance at time of last clinical assessment No invasive treatment for prostatic disease within the last 2 years Subject is free of clinically apparent/active autoimmune disease (no prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave's Disease, Hashimoto's Thyroiditis, Multiple Sclerosis, and Insulin Dependent Diabetes Mellitus). Note subjects with Non-Insulin Dependent Diabetes Mellitus can be included. Subject has adequate bone marrow function as defined by an Absolute Lymphocyte Count (ALC) ≥ 500/µL, Absolute Neutrophil Count (ANC) >1200/µL, Platelet Count >100,000/µL. Subject must practice a reliable form of contraception (barrier or vasectomy) while they are being treated with vaccines and another effective method of birth control must also be used by their partner Exclusion Criteria: Diagnosis of any cancer other than prostate cancer within the last 5 years (except basal cell carcinoma) Any suspicion of metastatic cancer Any Gleason grade 5 component in the prostatic biopsies Participation in another research study involving an investigational product in the 30 days preceding enrolment, or planned use during the study period Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate Seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) or HIV Any confirmed or suspected immunosuppressive or immunodeficient state, asplenia, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled/topical steroids are allowed) Platelet count >400,000/μL; Monocytes >80,000/μL; Hemoglobin <11g/dL Known allergy to neomycin History of allergic response to previous vaccinia vaccinations History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products History of hypersensitivity and haemorrhagic cystitis Any history of anaphylaxis Suspected or known current injecting drug or alcohol abuse (as defined by an alcohol intake of greater than 42 units per week) History of a serious psychiatric condition or other circumstance s that may be associated with not understanding or complying with the study protocol

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Freddie Hamdy

Organizational Affiliation

Oxford University Hospitals NHS Trust

Official's Role

Study Chair

Facility Information:

Facility Name

University of Oxford

City

Oxford

ZIP/Postal Code

OX3 7DQ

Country

United Kingdom

Facility Name

Royal Hallamshire Hospital

City

Sheffield

ZIP/Postal Code

S10 2IF

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

32591433

Citation

Cappuccini F, Bryant R, Pollock E, Carter L, Verrill C, Hollidge J, Poulton I, Baker M, Mitton C, Baines A, Meier A, Schmidt G, Harrop R, Protheroe A, MacPherson R, Kennish S, Morgan S, Vigano S, Romero PJ, Evans T, Catto J, Hamdy F, Hill AVS, Redchenko I. Safety and immunogenicity of novel 5T4 viral vectored vaccination regimens in early stage prostate cancer: a phase I clinical trial. J Immunother Cancer. 2020 Jun;8(1):e000928. doi: 10.1136/jitc-2020-000928.

Results Reference

derived

Learn more about this trial

Vaccination in Prostate Cancer (VANCE)

We'll reach out to this number within 24 hrs