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TENDU Vaccine in Patients With Relapse After Primary Radical Prostatectomy

Phase 1
Completed
Conditions
Prostate Cancer
Interventions
Biological: TENDU
Registration Number
NCT04701021
Lead Sponsor
Ultimovacs ASA
Brief Summary

This is a phase I, dose selection study of safety and effect of different doses of TENDU vaccine, a therapeutic peptide conjugate vaccine, in patients with relapse after primary radical prostatectomy.

Detailed Description

This is a open label dose selection study to investigate the safety, tolerability, immune response and preliminary clinical effect of different doses of the TENDU vaccine. TENDU is a synthetic therapeutic peptide conjugate vaccine intended for treatment of prostate cancer.

The patients enrolled in this study is adults with documented progressive disease after radical prostatectomy and who are eligible for salvage radiotherapy and short-term (6 months) androgen deprivation therapy.

All patients taking part at the study must be vaccinated with a Boostrix vaccine (including tetanus antigen) one week prior to the first TENDU vaccine treatment.

Three different doses, 40, 400 and 960 μg of the TENDU vaccine are to be investigated.

The vaccine is administrated by subcutaneous injections with one injection per drug substance (four separate injections) consecutively. The TENDU vaccine will be given four times during a treatment period lasting for 6 weeks and followed up for 6 months after the last treatment.

In total between 12 to 18 patients will be enrolled with a 3+3 design in each dose cohort. The first patient will receive the lowest dose of the TENDU vaccine, and after the treatment is completed, a safety evaluation will be done to evaluate enrolment of the next patients in this cohort. If one patient develops a dose limiting toxicity at a specific dose, an additional three patients are to be enrolled into that same dose cohort, and on the recommended dose an addition of 3 patients will be enrolled.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
12
Inclusion Criteria
  1. Males ≥18 years of age

  2. PSA rise >0.2 ng/mL less than 18 months following radical prostatectomy (RP) and pathological ISUP Grade 4-5 (Gleason score >7), or persisting PSA >0.1 ng/mL six weeks after RP and short PSA-DT, eligible for salvage radiotherapy and short term androgen deprivation therapy

  3. ECOG performance status 0 or 1

  4. Adequate organ function as indicated by the following laboratory values:

    • White blood cell count ≥ 2,500/μL
    • Absolute neutrophil count ≥ 1,000/μL
    • Platelets ≥ 100,000/μL
    • Haemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
    • Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
    • Serum total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN
    • AST and ALT ≤ 2.5 x ULN
  5. Patients with potential to father children must use an acceptable contraceptive method

  6. Written informed consent prior to any study-specific evaluations

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Exclusion Criteria
  1. History of hematologic or primary solid tumor malignancy other than prostate cancer with remission less than 3 years prior study enrolment.
  2. Metastatic disease assessed by PSMA PET/CT
  3. Hypersensitivity to the active substance or any of its excipients
  4. Current use of androgen deprivation therapy or radiotherapy to the pelvis
  5. Known history or any evidence of active, non-infectious pneumonitis
  6. History of New York Heart Association class 3-4 congestive heart failure or history of myocardial infarction within 6 months of starting study treatment
  7. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule.
  8. Active infection requiring systemic therapy
  9. Diagnosis of immunodeficiency
  10. Any use of immunosuppressive (cytotoxic chemotherapy, systemic steroids) or immunomodulating agents within 8 weeks of study entry.
  11. Hepatitis B or Hepatitis C or Human Immunodeficiency Virus positive
  12. Expected to require any other form of systemic or localized antineoplastic therapy during the study
  13. Received any other investigational therapy within 4 weeks of the first dose of study treatment
  14. Any medical, psychological, social or neurological condition that would make it difficult for the patient to participate in the study and comply with the study procedures, restrictions, and requirements
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TENDUTENDUThree different doses of the TENDU vaccine are to be investigated: 40, 400 and 960μg.
Primary Outcome Measures
NameTimeMethod
Assessment of safety and tolerability of TENDU vaccineTime from enrollment until 6 months after last dose

Frequency and severity of Adverse Events (AEs) graded according to CTCAE version 5.0.

Secondary Outcome Measures
NameTimeMethod
Assessment of Immunological responseTime from enrollment until 6 months after last dose

To evaluate the immunological response against the prostate specific peptides in the patients at baseline and after TENDU vaccinations.

Assessment of anti-tetanus protein and anti-MTTE titersTime from enrollment until 6 months after last dose

To evaluate the preliminary anti-tumor activity of the TENDU vaccine in patients pre- and post the vaccination with Boostrix (including tetanus antigen) and the TENDU vaccinations by evaluation of anti-tetanus protein and anti-MTTE titers.

Assessment of Anti-tumor activityTime from enrollment until 6 months after last dose

To evaluate the preliminary anti-tumor activity of the TENDU vaccine according to changes in the PSA, PAP, PSMA and PET/CT.

Trial Locations

Locations (1)

Oslo University Hospital, The Norwegian Radium Hospital

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Oslo, Norway

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