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

Condition: Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03040791

Sponsor: Hospital Moinhos de Vento

Phase: Phase 2


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

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.

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