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

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Cirmtuzumab

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
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • University Of California San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

Drug: Cirmtuzumab; Cirmtuzumab will be given in combination with docetaxel.; Other Names: Docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Study Chair: Rana McKay, UCSD

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2022
• Primary Completion (Actual): October 1, 2024
• Study Completion (Actual): October 1, 2024

Study Registration Dates

• First Submitted: December 1, 2021
• First Submitted That Met QC Criteria: December 1, 2021
• First Posted (Actual): December 14, 2021

Study Record Updates

• Last Update Posted (Estimated): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 5, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Docetaxel; Prostate cancer; ROR1; Wnt pathway; Cirmtuzumab
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: 19-1514

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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