The purpose of this study is to examine the safety and efficacy of cirmtuzumab in combination with standard of care docetaxel in patients with metastatic castration resistant prostate cancer. Docetaxel is a taxane chemotherapy which has been shown to prolong survival in men with castration resistant prostate cancer. Cirmtuzumab is a monoclonal antibody that targets the receptor called ROR1 of the non-canonical Wnt pathway and is suspected to contribute to prostate cancer growth and progression.
This study seeks to targeting the non-canonical Wnt pathway with an antibody against ROR1. ROR1 is an attractive target given its low expression in non-malignant tissues and its role in proliferation and survival in prostate cancer. From preclinical data in a variety of tumor types, blockade of ROR1 inhibits cell growth and cirmtuzumab has shown efficacy in clinical trials with CLL. Preclinical data suggests that ROR1 is upregulated in chemotherapy resistant cells and treatment with cirmtuzumab and a taxane achieved higher cytotoxic response than both agents alone, supporting the use of the combination of cirmtuzumab and a taxane. Based on the biological rationale behind cirmtuzumab and preclinical activity with docetaxel, this is an open label, phase 2 clinical trial to evaluate the safety and efficacy of cirmtuzumab in combination with docetaxel for the treatment of metastatic, castrate resistant prostate adenocarcinoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Cirmtuzumab will be given in combination with docetaxel.
University of California San Diego
La Jolla, California, United States
Recommended phase 2 dose of docetaxel combined with cirmtuzumab
Defined by CTCAE version 5 grading
Time frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Incidence of treatment-emergent adverse events
Defined by CTCAE version 5 grading
Time frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Total alkaline phosphatase response
Defined as a reduction of ≥30% from the baseline value, confirmed ≥4 weeks later.
Time frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Time to PSA progression
Defined by PCWG-3 criteria
Time frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Time to increase in the total alkaline phosphatase level
Defined as an increase of ≥25% from baseline at ≥12 weeks, in patients with no decrease from baseline, or as an increase of ≥25% above the nadir, confirmed ≥3 weeks later, in patients with an initial decrease from baseline.
Time frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Radiographic progression free survival
Defined by PCWG-3 criteria for bone metastases and RECIST version 1.1 for soft tissue
Time frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
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Time to first subsequent anti-cancer therapy
Time from study discontinuation to initiation of subsequent systemic anti-cancer therapy or death
Time frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Time to first symptomatic skeletal event
Time to first symptomatic pathologic fracture, radiation to the bone given symptomatic bone metastasis, surgery to the bone given symptomatic bone metastasis, or symptomatic spinal cord compression
Time frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Overall survival
Time from enrollment to death or last follow up
Time frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Composite clinical benefit
Composite endpoint of clinical benefit defined as any one of the following: PSA response by PCWG3 criteria, objective response rate by RECIST version 1.1, and stable disease \> 6 months by RECIST version 1.1.
Time frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months