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

Metastatic Castration-resistant Prostate Cancer Clinical Trial

Official title:

A Phase 1b Trial Investigating Docetaxel Combined With Cirmtuzumab in Patients With Metastatic Castration Resistant Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05156905
• Other study ID #: 19-1514
• Status: Recruiting
• Phase: Phase 1
• Start date: June 16, 2022
• Est. completion date: February 2026

Study information

• Verified date: November 2023
• Source: University of California, San Diego
• Contact: Rana R McKay, MD
• Phone: 858-822-6185
• Email: rmckay[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: February 2026
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Cirmtuzumab
Cirmtuzumab will be given in combination with docetaxel.

Locations

Country	Name	City	State
United States	University of California San Diego	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended phase 2 dose of docetaxel combined with cirmtuzumab	Defined by CTCAE version 5 grading	Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Secondary	Incidence of treatment-emergent adverse events	Defined by CTCAE version 5 grading	Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Secondary	Total alkaline phosphatase response	Defined as a reduction of =30% from the baseline value, confirmed =4 weeks later.	Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Secondary	Time to PSA progression	Defined by PCWG-3 criteria	Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Secondary	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.	Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Secondary	Radiographic progression free survival	Defined by PCWG-3 criteria for bone metastases and RECIST version 1.1 for soft tissue	Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Secondary	Time to first subsequent anti-cancer therapy	Time from study discontinuation to initiation of subsequent systemic anti-cancer therapy or death	Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Secondary	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	Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Secondary	Overall survival	Time from enrollment to death or last follow up	Patients will be followed from study entry to death or date last known alive, assessed up to 36 months
Secondary	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.	Patients will be followed from study entry to death or date last known alive, assessed up to 36 months