Chemotherapy, Immunotherapy and PARP Inhibitor for the Treatment of Metastatic Aggressive Variant Prostate Cancer

About the Study

This study will look at how well the combination of chemotherapy drugs (such as cabazitaxel and carboplatin), a PARP inhibitors (niraparib), and an immunotherapy agents (cetrelimab) works for treating people with a rare type of prostate cancer known as aggressive variant prostate cancer (AVPC). The research will compare the benefits of giving niraparib with or without cetrelimab, after treatment with chemotherapy.

Type of Study

This is a two-arm, randomized, open-label study.

• Participants will be placed into one of two study groups by chance, neither the participants nor the researchers choose the group into which the participants are placed. Participants will be told which group they have been assigned to. 
• Participants will have treatment in two phases during this study. During Phase 1, the induction phase, participants will all receive the same treatment with chemotherapy and immunotherapy. Phase 2, the maintenance phase will begin after participants have completed chemotherapy and immunotherapy. During Phase 2, participants in each group will receive different treatment. 
  • Group 1 will receive treatment with a PARP inhibitor.  
  • Group 2 will receive treatment with a PARP inhibitor combined with an immunotherapy.

What the Study Involves

Induction phase

• Patients in both groups will receive the chemotherapy agents cabazitaxel intravenously (IV) and carboplatin IV on day 1.
• Beginning in cycle 2, all patients will also receive the immunotherapy cetrelimab IV on day 1.
• Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Maintenance phase

• Group 1
  • Participants will take niraparib orally each day on days 1-28.
  • Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Group 2
  • Participants will receive cetrelimab IV on day 1.
  • Participants will take niraparib orally each day on days 1-28.
  • Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Study participants will be followed up to 5 years.

Study Site

• Houston, Texas
  MD Anderson Cancer Center   
  Contact: Ana Aparicio by phone: 713-563-6969 or by email: [email protected]    
  Lead Researcher: Ana Aparicio 

Men age 18 years or older who meet the following criteria:

• Has metastatic prostate cancer, with evidence of disease progression
• Meets at least one of the following criteria of AVPC:
  • Small cell (neuroendocrine) prostate cancer.
  • Exclusive visceral metastases.
  • Mostly lytic bone metastases identified by plain x-ray or CT scan
  • Bulky lymph node enlargement or high-grade tumor mass in prostate/pelvis.
  • Low PSA (10 ng/mL or less) at initial diagnosis and high volume (20 or more) bone metastases.
  • Developed castration resistance a short time after beginning hormonal therapy.
  • Tumor mutation or loss of function in at least two of the following three genes: TP53, RB1 and PTEN.
• Must provide tissue samples at specified timepoints during the study.
• Surgical or chemical castration, with baseline testosterone levels of 50 ng/dL or less.

Check clinicaltrials.gov for additional eligibility. 

• Had prior treatment for castration-resistant prostate cancer with carboplatin, cisplatin, cabazitaxel, PARP-inhibitor or an anti-PD1 or anti-PDL1 inhibitor
• Received more than one treatment of chemotherapy
• Not recovered from adverse events, major surgery, or radiation for the treatment of prostate cancer
• An additional malignancy (other than the one treated in this study) which has a >= 30% probability of recurrence within 24 months
• Active or prior documented autoimmune or inflammatory disorders (Contact the Study Team for a list of exceptions)