Nivolumab in Prostate Cancer With DNA Repair Defects (ImmunoProst Trial)

• Register: ClinicalTrials.gov
• Last refreshed on: 7 September 2021
• Main ID: NCT03040791
• Date of registration: 27/01/2017
• Prospective Registration: Yes
• Primary sponsor: Hospital Moinhos de Vento
• Public title: Nivolumab in Prostate Cancer With DNA Repair Defects (ImmunoProst Trial) ImmunoProst
• Scientific title: Nivolumab in Prostate Cancer With DNA Repair Defects (ImmunoProst Trial)
• Date of first enrolment: June 1, 2018
• Target sample size: 38
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03040791
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Brazil

Contacts

• Name: Pedro Isaacsson, MD
• Affiliation: Hospital Moinhos de Vento

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the prostate with tumor tissue available
for molecular analyses. If archival tissue for biomarker analysis is not available
then the patient must be willing to have a further biopsy to obtain tumor tissue for
histological diagnosis.

2. Metastatic Castrate-resistant prostate cancer (mCRPC), defined by:

- Disease progression despite androgen deprivation therapy (ADT) and may present as
either a continuous rise in serum prostate-specific antigen (PSA) levels, the
progression of pre-existing disease, and/or the appearance of new metastases.

- Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0
nM). If the patient is being treated with GnRH or LHRH agonists or antagonists
(patient who have not undergone orchiectomy), this therapy should be maintained.

3. Documented prostate cancer progression, during treatment with Docetaxel, as assessed
by the investigator with one of the following:

- PSA progression is defined according the PCWG3 criteria: PSA increase, that is =
50% and = 2 ng/mL above the nadir, and which is confirmed by a second value = 3
weeks later (confirmed the rising trend).

- Radiographic progression of visceral lesions or soft tissue disease by modified
RECIST 1.1 criteria.

- Progression of bone metastasis is defined according the Appendix B: Prostate
Cancer Clinical Trials Working Group 3 (Adapted) two or more documented new bone
lesions on a bone scan with or without PSA progression. Confirmation of ambiguous
results by other imaging modalities (eg, CT or MRI) is obligatory. If Docetaxel
chemotherapy is used more than once, this will be considered as one regimen.

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2 Appendix A:
Performance Status Criteria

5. Life expectancy > 24 weeks.

6. Age = 18 years

7. At least 28 days since the completion of any prior anti-cancer therapy (except for
LHRH agonists or antagonists), including chemotherapy (taxane-based). Additionally,
clinically relevant treatment toxicities should have resolved to grade 1 or less prior
to start study treatment.

8. For hormonal treatment must be followed the guideline below:

- No antiandrogens are allowed during the study period. The use of antiandrogens
before study entry is permitted, but at least 28 days since the completion of
prior antiandrogen are required (washout period).

- Corticosteroids dose > Prednisolone 10 mg/day (or equivalent) are allowed only if
clinically indicated for medical conditions. At least 28 days since the
completion of prior corticotherapy are required (washout period).

9. Agreeable to have all the biomarker studies including the fresh tumor biopsies if
needed.

10. Patients must have adequate organ function within 1 weeks prior enrollment to and
evidenced by:

- Hemoglobin = 9.0 g/dL

- WBC > 2.000/mm3

- Absolute neutrophil count = 1.500/mm3

- Platelet count = 100.000/mm3

- Creatinine Clearance = 30 mL/min. Creatinine Clearance (CrCl) must be calculated
at screening using the Cockcroft-Gault formula:

- Bilirubin < 3 x upper limit of normal (ULN) except for patients with known
Gilbert's syndrome.

- Aspartate transaminase (AST) (SGOT) < 3.0 x ULN.

- Alanine transaminase (ALT) (SGPT) < 3.0 x ULN.

- No cardiac disease defined by as active angina, symptomatic congestive heart
failure, or myocardial infarction within previous six months.

Exclusion Criteria:

- Patients with any active known or suspected autoimmune disease. Patients with
vitiligo, type I diabetes mellitus, controlled autoimmune hypothyroidism, psoriasis
not requiring systemic treatment, or other conditions under control are permitted to
enroll.

- Patients with conditions that needs systemic corticosteroids dose > Prednisolone 10
mg/day (or equivalent) or other immunosuppressive medications within 28 days prior to
the first dose of study drug. Inhaled steroids are permitted if necessary.

- Patients with any known active chronic liver disease.

- Patients who have prior history of malignancy treated with curative intention in the
past 2 years with the exception of basal cell carcinoma and squamous cell carcinoma of
the skin, which were allowed in any case. Patients with other malignancies that do not
fulfill the prior criteria could be considered for recruitment if they do not
represent a competitive cause of death and have a low potential to progress to
metastatic progression. Patients in this condition may be enrolled in the trial if
approved after review by principal investigator.

- Known history of testing positive for human immunodeficiency virus (HIV), known
acquired immunodeficiency syndrome (AIDS), or any positive test for hepatitis B or
hepatitis C virus representing acute or chronic disease.

- Preceding treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody, or any
other antibody or drug specifically targeting T-cell co-stimulation or checkpoint
pathways.

- Major surgery less than 28 days prior to the first dose of study drug.

- Radiation therapy less than 14 days prior to the first dose of study drug.



Age minimum: 18 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Prostate Cancer

Intervention(s)

Drug: Nivolumab

Primary Outcome(s)

PSA response rate [Time Frame: through study completion, an average of 1 year]

Secondary Outcome(s)

Overall survival [Time Frame: through study completion, an average of 1 year]

Time to PSA progression [Time Frame: through study completion, an average of 1 year]

Radiological progression-free survival (rPFS) [Time Frame: through study completion, an average of 1 year]

Progression free survival (PFS) [Time Frame: through study completion, an average of 1 year]

PSA Response Rate at 6 and 12 months [Time Frame: through study completion, an average of 1 year]

Time to Radiographic Progression [Time Frame: through study completion, an average of 1 year]

Secondary ID(s)

64121317.4.1001.5330

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Bristol-Myers Squibb