Back to resultsStudy of Docetaxel Combined With Cirmtuzumab in Metastatic Castration Resistant Prostate Cancer
Primary Purpose
Metastatic Castration-resistant Prostate Cancer
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cirmtuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Castration-resistant Prostate Cancer focused on measuring Prostate cancer, Docetaxel, Wnt pathway, Cirmtuzumab, ROR1
Eligibility Criteria
Inclusion Criteria:
- Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate. Patients with neuroendocrine component are eligible.
- Participants must have castrate levels of serum testosterone < 50 ng/dL.
- Participants without orchiectomy must be maintained on luteinizing hormone releasing hormone (LHRH) agonist/antagonist.
- Participants must have received prior abiraterone and/or next generation androgen receptor antagonist (enzalutamide, apalutamide, or darolutamide) for hormone sensitive disease or CRPC. Prior docetaxel for hormone sensitive disease is permitted.
- Participants must have progressive disease. Patients with non-measurable disease are eligible.
- Eastern Cooperative Oncology Group performance status ≤1 (Karnofsky ≥80%).
- Patients must have normal organ and marrow function.
Exclusion Criteria:
- No pure small cell carcinoma.
- Prior treatment with cirmtuzumab.
- No prior treatment with docetaxel for CRPC.
- Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation. Treatment with cytotoxic chemotherapy within 3 weeks of treatment initiation. Treatment enzalutamide or other investigational prostate cancer directed therapy within 4 weeks of treatment initiation.
- Palliative radiation therapy to the bone or other sites within 2 weeks of treatment initiation.
- Imminent or established spinal cord compression based on clinical and/or imaging findings.
- Known active central nervous system metastases and/or carcinomatous meningitis.
- Uncontrolled intercurrent illness or clinically significant medical condition.
- Treatment with antimicrobial agent within 4 weeks of treatment initiation.
Sites / Locations
- University of California San DiegoRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cirmtuzumab + Docetaxel
Arm Description
There is only one treatment arm on this study. The combination of cirmtuzumab + docetaxel will be administered on one treatment arm. Treatment will cirmtuzumab will be administered initially as a loading dose alone on days 1, 15, and 29 of cycle 1. Following the loading, cirmtuzumab will be given on Day 1 of every 21-day cycle starting on Cycle 2 to up to Cycle 7 corresponding with concurrent docetaxel administration. Following discontinuation or completion of docetaxel, treatment with cirmtuzumab will be continued Day 1 of every 28 cycle until disease progression, toxicity or study withdrawal. Docetaxel will be administered on day 1 of every 21-day cycle starting Cycle 2 for up to 6 cycles.
Outcomes
Primary Outcome Measures
Recommended phase 2 dose of docetaxel combined with cirmtuzumab
Defined by CTCAE version 5 grading
Secondary Outcome Measures
Incidence of treatment-emergent adverse events
Defined by CTCAE version 5 grading
Total alkaline phosphatase response
Defined as a reduction of ≥30% from the baseline value, confirmed ≥4 weeks later.
Time to PSA progression
Defined by PCWG-3 criteria
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.
Radiographic progression free survival
Defined by PCWG-3 criteria for bone metastases and RECIST version 1.1 for soft tissue
Time to first subsequent anti-cancer therapy
Time from study discontinuation to initiation of subsequent systemic anti-cancer therapy or death
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
Overall survival
Time from enrollment to death or last follow up
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.
Full Information
NCT ID
NCT05156905
First Posted
December 1, 2021
Last Updated
October 11, 2022
Sponsor
University of California, San Diego
1. Study Identification
Unique Protocol Identification Number
NCT05156905
Brief Title
Study of Docetaxel Combined With Cirmtuzumab in Metastatic Castration Resistant Prostate Cancer
Official Title
A Phase 1b Trial Investigating Docetaxel Combined With Cirmtuzumab in Patients With Metastatic Castration Resistant Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 16, 2022 (Actual)
Primary Completion Date
February 2025 (Anticipated)
Study Completion Date
February 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Diego
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castration-resistant Prostate Cancer
Keywords
Prostate cancer, Docetaxel, Wnt pathway, Cirmtuzumab, ROR1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cirmtuzumab + Docetaxel
Arm Type
Experimental
Arm Description
There is only one treatment arm on this study. The combination of cirmtuzumab + docetaxel will be administered on one treatment arm. Treatment will cirmtuzumab will be administered initially as a loading dose alone on days 1, 15, and 29 of cycle 1. Following the loading, cirmtuzumab will be given on Day 1 of every 21-day cycle starting on Cycle 2 to up to Cycle 7 corresponding with concurrent docetaxel administration. Following discontinuation or completion of docetaxel, treatment with cirmtuzumab will be continued Day 1 of every 28 cycle until disease progression, toxicity or study withdrawal. Docetaxel will be administered on day 1 of every 21-day cycle starting Cycle 2 for up to 6 cycles.
Intervention Type
Drug
Intervention Name(s)
Cirmtuzumab
Other Intervention Name(s)
Docetaxel
Intervention Description
Cirmtuzumab will be given in combination with docetaxel.
Primary Outcome Measure Information:
Title
Recommended phase 2 dose of docetaxel combined with cirmtuzumab
Description
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
Secondary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events
Description
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
Title
Total alkaline phosphatase response
Description
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
Title
Time to PSA progression
Description
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
Title
Time to increase in the total alkaline phosphatase level
Description
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
Title
Radiographic progression free survival
Description
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
Title
Time to first subsequent anti-cancer therapy
Description
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
Title
Time to first symptomatic skeletal event
Description
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
Title
Overall survival
Description
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
Title
Composite clinical benefit
Description
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate. Patients with neuroendocrine component are eligible.
Participants must have castrate levels of serum testosterone < 50 ng/dL.
Participants without orchiectomy must be maintained on luteinizing hormone releasing hormone (LHRH) agonist/antagonist.
Participants must have received prior abiraterone and/or next generation androgen receptor antagonist (enzalutamide, apalutamide, or darolutamide) for hormone sensitive disease or CRPC. Prior docetaxel for hormone sensitive disease is permitted.
Participants must have progressive disease. Patients with non-measurable disease are eligible.
Eastern Cooperative Oncology Group performance status ≤1 (Karnofsky ≥80%).
Patients must have normal organ and marrow function.
Exclusion Criteria:
No pure small cell carcinoma.
Prior treatment with cirmtuzumab.
No prior treatment with docetaxel for CRPC.
Treatment with abiraterone, apalutamide, or darolutamide within 2 weeks of treatment initiation. Treatment with cytotoxic chemotherapy within 3 weeks of treatment initiation. Treatment enzalutamide or other investigational prostate cancer directed therapy within 4 weeks of treatment initiation.
Palliative radiation therapy to the bone or other sites within 2 weeks of treatment initiation.
Imminent or established spinal cord compression based on clinical and/or imaging findings.
Known active central nervous system metastases and/or carcinomatous meningitis.
Uncontrolled intercurrent illness or clinically significant medical condition.
Treatment with antimicrobial agent within 4 weeks of treatment initiation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rana R McKay, MD
Phone
858-822-6185
Email
rmckay@health.ucsd.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rana McKay
Organizational Affiliation
UCSD
Official's Role
Study Chair
Facility Information:
Facility Name
University of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rana R McKay, MD
Phone
858-822-6185
Email
rmckay@health.ucsd.edu
12. IPD Sharing Statement
Learn more about this trial
Study of Docetaxel Combined With Cirmtuzumab in Metastatic Castration Resistant Prostate Cancer
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