Trial Title:
Dose-Escalation Study of Cabozantinib in Combination With Lutetium-177 (177Lu)-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer
NCT ID:
NCT05613894
Condition:
Metastatic Castration-resistant Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Pluvicto
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cabozantinib
Description:
(177Lu)-PSMA-617 will be administered every 6 weeks for up to 6 cycles per SOC. Oral
Cabozantinib taken daily at home.
Arm group label:
Dose Escalation (Part 1)
Arm group label:
Dose Expansion Cohort (Part 2)
Other name:
177Lu-PSMA-617
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).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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 have been previously treated with at least 2 cycles of a taxane containing
regimen (such as docetaxel or cabazitaxel).
- ≥ 1 PSMA-positive lesion and/or metastatic disease that is predominantly PSMA
positive and with no dominant PSMA-negative metastatic lesion.
- 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 ≥ 30 mL/min by Cockcroft-Gault formula
- 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.
- Patients must have a life expectancy >3 months.
Exclusion Criteria:
- 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:
- The subject has evidence of tumor invading the GI tract, active peptic
ulcer disease, inflammatory bowel disease (e.g., Crohn's disease),
diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis,
acute pancreatitis, acute obstruction of the pancreatic duct or common
bile duct, or gastric outlet obstruction.
- Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal
abscess within 6 months before first dose of study treatment.
- Note: Complete healing of an intra-abdominal abscess must be confirmed
before first dose of study treatment.
- Any other condition that would, in the Investigator's judgment, contraindicate
the subject's participation in the clinical study due to safety concerns or
compliance with clinical study procedures (e.g., infection/inflammation,
intestinal obstruction, unable to swallow medication, social/ psychological
issues, etc.)
- Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5
ml) of red blood, or other history of significant bleeding (e.g., pulmonary
hemorrhage) within 12 weeks before first dose of study treatment.
- Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease
manifestation.
- Lesions invading or encasing any major blood vessels
- Other clinically significant disorders that would preclude safe study participation.
- Serious non-healing wound/ulcer/bone fracture.
- Uncompensated/symptomatic hypothyroidism.
- Moderate to severe hepatic impairment (Child-Pugh B or C).
- Known history of COVID-19 unless the subject has clinically recovered from the
disease at least 30 days prior to first dose of study treatment.
- Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of
brain metastasis) within 2 weeks before first dose of study treatment or minor
surgeries within 10 days before first dose of study treatment.
- Subjects must have complete wound healing from major surgery or minor surgery before
first dose of study treatment.
--Subjects with clinically relevant ongoing complications from prior surgery are not
eligible.
- Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per
electrocardiogram (ECG) within 14 days before first dose of study treatment.
--Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional
ECGs at intervals of approximately 3 min must be performed within 30 min after the
initial ECG, and the average of these three consecutive results for QTcF will be
used to determine eligibility.
- Inability to swallow tablets
- Previously identified allergy or hypersensitivity to components of the study
treatment formulations.
- Known HIV infection with a detectable viral load within 6 months of the anticipated
start of treatment.
--Note: Subjects on effective antiretroviral therapy with an undetectable viral load
within 6 months of the anticipated start of treatment are eligible for this trial.
- Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination, radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), or
hepatitis C.
- Note: Subjects with a past or resolved HBV infection (defined as the presence of
hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects
positive for hepatitis C (HCV) antibody are eligible only if polymerase chain
reaction is negative for HCV RNA.
- Medical, psychiatric, cognitive, or other conditions that may compromise the
subject's ability to understand the subject information, give informed consent,
comply with the study protocol or complete the study.
- Subjects taking prohibited medications as described in Section 6.8.2. A washout
period of prohibited medications for a period of at least five half-lives or as
clinically indicated should occur before the start of treatment.
Gender:
Male
Gender based:
Yes
Gender description:
male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Huntsman Cancer Institute at University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Susan Sharry
Phone:
801-585-3453
Email:
susan.sharry@hci.utah.edu
Start date:
July 14, 2023
Completion date:
May 1, 2028
Lead sponsor:
Agency:
University of Utah
Agency class:
Other
Collaborator:
Agency:
Exelixis
Agency class:
Industry
Source:
University of Utah
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05613894
