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

Paused · Phase 1

Conditions studied: Metastatic Castration-resistant Prostate Cancer

In brief

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).

Key facts

Study ID

NCT05613894

Run by

University of Utah

People needed

33

Starts

2023-07-14

Expected to finish

2028-12-01

Last updated by the study team

2026-06-29

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

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
• Hepatic:
• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
• For subjects with Gilbert's disease: ≤ 3x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN).
• Renal:
• Urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g
• Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula Males: ((140-age)×weight[kg])/(serum creatinine [mg/dL]×72)
• Sexually active fertile patients and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 6 months after the last dose of study treatment in accordance with section 5.4.2.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

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.
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH)
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
• Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before the first dose of study treatment.
• Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion 14) for at least 1 week before first dose of study treatment.
• Uncontrolled hypertension defined as sustained blood pressure (BP) ≥ 150 mm Hg systolic or >90 mmHg diastolic despite optimal antihypertensive treatment.
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:

Where it is running

• Huntsman Cancer Institute at University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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