A Phase 2 Clinical Trial of Pembrolizumab in Combination With Carboplatin and Cabazitaxel in Aggressive Variant Metastatic Castration Resistant Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Prostate Cancer Metastatic
- Sponsor
- Fundacion Oncosur
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Safety - Adverse Events
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
It is a Phase 2 clinical trial of Pembrolizumab in combination with Carboplatin and Cabazitaxel in Aggressive Variant Metastatic Castration Resistant Prostate Cancer.
It is divided into two parts: an induction period of 6 cycles of 3 weeks each cycle of Pembrolizumab+Cabazitaxel+Carboplatino and a maintenance phase of 15 cycles of 6 weeks each cycle of Pembrolizumab.
Detailed Description
Aggressive variant prostate cancer is a clinically defined subset of metastatic castration resistant prostate cancers characterized by the absence of response to AR targeted agents and neuroendocrine features. The treatments that are currently available are not effective and represent an unmet clinical need. This subgroup has been molecularly characterized and associate loss of key tumor suppressors, including TP53, PTEN and RB, and neuroendocrine features. Carboplatin and cabazitaxel have demonstrated promising activity in this scenario although virtually all patients succumb to the disease. Pembrolizumab has demonstrated activity in neuroendocrine tumors. In this trial will be evaluated the activity and safety of pembrolizumab in combination with the most active chemotherapy regiment available to date in aggressive variant prostate cancer, carboplatin plus cabazitaxel
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male participants who are at least 18 years of age on the day of signing informed consent
- •Histologically confirmed diagnosis of adenocarcinoma and/or neuroendocrine carcinoma of the prostate will be enrolled in this study
- •Presence of metastatic disease documented on imaging studies (bone scan, computed tomography (CT) and/or magnetic resonance imaging (MRI) scans
- •At least one of the following Aggressive Variant Prostate Cancer (AVPC) Criteria
- •Histologically proven small cell (neuroendocrine) prostate cancer
- •Exclusive visceral metastases
- •Predominantly lytic bone metastases
- •Bulky lymph nodes (≥ 5 cm in longest dimension) or high-grade pelvic/prostatic masses
- •Low PSA (≤10 ng/ml) at initial presentation in the presence of extensive disease (≥20 metastases)
- •Elevated serum Lactate Dehydrogenase (LDH) (≥2 x ULN) or carcinoembryonic antigen (CEA) (≥2 x Upper limit (UL))
Exclusion Criteria
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), OX-40, CD137).
- •Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to informed consent signature.
- •Has received previous treatment with cabazitaxel or carboplatin.
- •Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (non-CNS) disease.
- •Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
- •Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- •Known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
- •Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
- •Has severe hypersensitivity (≥Grade 3) to pembrolizumab, carboplatin or cabazitaxel and/or any of its excipients.
Arms & Interventions
Study Arm
6 cycles of Pembrolizumab+Cabazitaxel+Carboplatin + 15 cycles of Pembrolizumab
Intervention: Pembrolizumab
Study Arm
6 cycles of Pembrolizumab+Cabazitaxel+Carboplatin + 15 cycles of Pembrolizumab
Intervention: Carboplatin
Study Arm
6 cycles of Pembrolizumab+Cabazitaxel+Carboplatin + 15 cycles of Pembrolizumab
Intervention: Cabazitaxel
Outcomes
Primary Outcomes
Safety - Adverse Events
Time Frame: through study completion, an average of 2 years
Incidence of adverse events (AEs) graded according to NCI-CTCAE v 5.0 criteria
Efficacy - Radiographic Progression-Free Survival rate
Time Frame: 6 months
To assess the safety of pembrolizumab in combination with carboplatin and cabazitaxel according to 6 months Radiographic Progression-Free Survival rate (rPFS) according to the Prostate Cancer Working Group 3 (PCWG3 ).
Secondary Outcomes
- Efficacy - PSA response(through study completion, an average of 2 years)
- Efficacy - overall survival(through study completion, an average of 2 years)
- Efficacy - progression-free survival(through study completion, an average of 2 years)
- Efficacy - Progression Free-Survival(12 months)
- Efficacy - Response rate(through study completion, an average of 2 years)
- Efficacy - PSA progression-free survival(through study completion, an average of 2 years)