Dose-Escalation Study of Cabozantinib in Combination With Lutetium-177 (177Lu)-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer

NCT05613894 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCI157278
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, phase 1b dose-escalation study of cabozantinib in combination with 177Lu-PSMA-617 in subjects with mCRPC. The primary hypothesis is that cabozantinib with 177Lu-PSMA will be safe and have efficacy in patients with mCRPC. The dose-escalation phase (Part 1) will assess the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period and identify the MTD and/or recommended dose and schedule for the subsequent expansion phase (Part 2).

Conditions

Metastatic Castration-resistant Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• The rate of dose-limiting toxicities (DLTs) during the DLT evaluation period

  To determine the maximum tolerated dose (MTD) and recommended dose and schedule for the subsequent Expansion Stage of daily oral administration of cabozantinib in subjects with metastatic castration-resistant prostate cancer (mCRPC) when taken in combination with 177Lu-PSMA-617

  28 days

• The proportion of patients without progression as defined by PCWG3-modified RECIST 1.1 at 24 weeks.

  To evaluate preliminary efficacy by estimating the progression-free survival (PFS) at 24 weeks (PFS24w) as assessed by per PCWG3-modified RECIST v1.1

  24 weeks

Secondary Outcomes (8)

• The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NCI CTCAE, version 5.0), seriousness, duration, and relationship to study treatment.

  up to 2 years

• ORR, defined as the proportion of subjects with measurable disease achieving a confirmed PR and CR as defined by PCWG3-modified RECIST 1.1.

  3 years

• DoR, defined as the interval of time from the date of initial documented response (PR or better per PCWG3-modified RECIST 1.1) to the time of progression from the best response, the start of a new therapy, or death from any cause.

  up to 3 years

• rPFS as assessed by PCWG3-modified RECIST 1.1 from start of therapy to the time of radiographic progression or death from any cause.

  up to 3 years

• The proportion of patients without progression as defined by PCWG3-modified RECIST 1.1 at 38 weeks.

  38 weeks

Study Arms (2)

Dose Escalation (Part 1)

EXPERIMENTAL

Part 1 will assess the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period and identify the MTD and/or recommended dose and schedule

Drug: Cabozantinib

Dose Expansion Cohort (Part 2)

EXPERIMENTAL

Expansion Phase to assess identified MTD and schedule from Part 1.

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

(177Lu)-PSMA-617 will be administered every 6 weeks for up to 6 cycles per SOC. Oral Cabozantinib taken daily at home.

Also known as: 177Lu-PSMA-617

Dose Escalation (Part 1); Dose Expansion Cohort (Part 2)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subject aged ≥ 18 years.
• Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology.
• Prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\<50 ng/dL or \<1.7 nmol/L).
• Prior treatment with at least one prior Novel Hormone Therapy (NHT), defined as second-generation anti-androgen therapies that include, but are not limited to, abiraterone acetate, enzalutamide, apalutamide, and darolutamide.
• Must be eligible for therapy with 177Lu-PSMA-617 and have ≥ 1 PSMA-positive lesion per treating investigator.
• Must have progressive mCRPC per the treating investigator.
• ECOG Performance Status ≤ 1.
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor support
• White blood cell count ≥ 3000/µL.
• Platelet count ≥ 100,000/µL
• Hemoglobin ≥ 9g/dL
• Serum albumin ≥ 2.5 g/dl
• PT/INR or partial thromboplastin time (PTT) test \< 1.3x the laboratory ULN

You may not qualify if:

• Receiving other investigational anti-cancer agents.
• Prior treatment with cabozantinib
• Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation within 6 months prior to randomization.
• Previous PSMA-targeted radioligand therapy
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment.
• Systemic treatment with radionuclides within 6 weeks before first dose of study treatment.
• Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis).
• Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment.
• Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment.
• Major surgery within 4 weeks prior to starting study drug, minor surgery within 10 days, or subjects who have not fully recovered from major surgery.
• Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the breast.

Sponsors & Collaborators

• University of Utah: lead
• Exelixis: collaborator

Study Sites (1)

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Interventions

cabozantinib; Pluvicto

Study Officials

• Umang Swami, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susan Sharry

CONTACT

801-585-3453; susan.sharry@hci.utah.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A standard 3+3 dose escalation design will be used to identify the MTD and/or recommended dose and schedule for the subsequent expansion phase. The study will test 2 dose levels of cabozantinib with the option to dose reduce to dose level -1.

Study Record Dates

• First Submitted: November 4, 2022
• First Posted: November 14, 2022
• Study Start: July 14, 2023
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2028
• Last Updated: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)