Study of Docetaxel Combined With Cirmtuzumab in Metastatic Castration Resistant Prostate Cancer

• ClinicalTrials.gov Identifier: NCT05156905
• Recruitment Status: Recruiting
• First Posted: December 14, 2021
• Last Update Posted: November 13, 2023
• Sponsor: University of California, San Diego
• Information provided by (Responsible Party): Rana Mckay, University of California, San Diego

Tracking Information

• First Submitted Date: December 1, 2021
• First Posted Date: December 14, 2021
• Last Update Posted Date: November 13, 2023
• Actual Study Start Date: June 16, 2022
• Estimated Primary Completion Date: February 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 5, 2022)

Recommended phase 2 dose of docetaxel combined with cirmtuzumab [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]

Defined by CTCAE version 5 grading

Original Primary Outcome Measures (submitted: December 1, 2021)

Composite clinical benefit [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]

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.

Current Secondary Outcome Measures (submitted: September 5, 2022)

• Incidence of treatment-emergent adverse events [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Defined by CTCAE version 5 grading
• Total alkaline phosphatase response [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Defined as a reduction of ≥30% from the baseline value, confirmed ≥4 weeks later.
• Time to PSA progression [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Defined by PCWG-3 criteria
• Time to increase in the total alkaline phosphatase level [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  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 [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Defined by PCWG-3 criteria for bone metastases and RECIST version 1.1 for soft tissue
• Time to first subsequent anti-cancer therapy [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Time from study discontinuation to initiation of subsequent systemic anti-cancer therapy or death
• Time to first symptomatic skeletal event [ 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 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 Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Time from enrollment to death or last follow up
• Composite clinical benefit [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  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.

Original Secondary Outcome Measures (submitted: December 1, 2021)

• Safety and tolerability [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Defined by CTCAE version 5 grading
• Total alkaline phosphatase response [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Defined as a reduction of ≥30% from the baseline value, confirmed ≥4 weeks later.
• Time to PSA progression [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Defined by PCWG-3 criteria
• Time to increase in the total alkaline phosphatase level [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  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 [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Defined by PCWG-3 criteria for bone metastases and RECIST version 1.1 for soft tissue
• Time to first subsequent anti-cancer therapy [ Time Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Time from study discontinuation to initiation of subsequent systemic anti-cancer therapy or death
• Time to first symptomatic skeletal event [ 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 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 Frame: Patients will be followed from study entry to death or date last known alive, assessed up to 36 months ]
  Time from enrollment to death or last follow up

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Castration-resistant Prostate Cancer

Intervention

Drug: Cirmtuzumab

Cirmtuzumab will be given in combination with docetaxel.

Other Name: Docetaxel

Study Arms

Experimental: Cirmtuzumab + Docetaxel

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: Drug: Cirmtuzumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 1, 2021): 32
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2026
• Estimated Primary Completion Date: February 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate. Patients with neuroendocrine component are eligible.
2. Participants must have castrate levels of serum testosterone < 50 ng/dL.
3. Participants without orchiectomy must be maintained on luteinizing hormone releasing hormone (LHRH) agonist/antagonist.
4. 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.
5. Participants must have progressive disease. Patients with non-measurable disease are eligible.
6. Eastern Cooperative Oncology Group performance status ≤1 (Karnofsky ≥80%).
7. Patients must have normal organ and marrow function.

Exclusion Criteria:

1. No pure small cell carcinoma.
2. Prior treatment with cirmtuzumab.
3. No prior treatment with docetaxel for CRPC.
4. 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.
5. Palliative radiation therapy to the bone or other sites within 2 weeks of treatment initiation.
6. Imminent or established spinal cord compression based on clinical and/or imaging findings.
7. Known active central nervous system metastases and/or carcinomatous meningitis.
8. Uncontrolled intercurrent illness or clinically significant medical condition.
9. Treatment with antimicrobial agent within 4 weeks of treatment initiation.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Rana R McKay, MD; 858-822-6185; rmckay@health.ucsd.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05156905
• Other Study ID Numbers: 19-1514
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Rana Mckay, University of California, San Diego
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, San Diego
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Rana McKay; UCSD

• PRS Account: University of California, San Diego
• Verification Date: November 2023