Overview
Multicenter Phase 3 study of 177Lu-TLX250 in adult participants with CAIX-expressing advanced, relapsed or recurrent clear cell renal cell carcinoma (ccRCC). Part 1 will evaluate two dosing regimens to determine the recommended Phase 3 dose (RP3D). Part 2 will compare 177Lu-TLX250 with investigator's choice of monotherapy aligned with Australian standard-of-care.
Description
This is a randomized, open-label, multi-center 3 study evaluating the safety and efficacy of 177Lu-TLX250, a CAIX-targeting radioligand therapy, in adult participants with advanced, relapsed or recurrent clear cell renal cell carcinoma (ccRCC).
The study consists of two parts:
• Part 1 (Phase 2a - Dose Optimization): Participants will be randomized to receive one of two dosing regimens of 177Lu-TLX250.
The objective of Part 1 is to determine the recommended Phase 3 dose (RP3D) for use in Part 2.
Eligibility
Inclusion Criteria:
- Women, age 60 years and older.
- Medically documented pure stress urinary incontinence on physical exam or urodynamic testing.
- Normal mammogram within the last 12 months
- Endometrial thickness of ≤4 mm in women with an intact uterus assessed by endometrial ultrasound.
- Ability and willingness to provide informed consent.
Exclusion Criteria:
- • Medically documented urge or mixed urinary incontinence (stress and urge) on physical exam or urodynamic testing.
- Participating in pelvic floor muscle training (PFMT) therapy currently or in the past 3 months
- Previous pelvic surgery (i.e., hysterectomy, pelvic organ prolapse repair, mid-urethral sling placement, injection of urethral bulking agents) or radiation treatment to the pelvis.
- History of ≥ Grade 3 pelvic organ prolapse
- Neurologic disorder causing UI or bladder dysfunction (i.e., multiple sclerosis, Parkinson's disease, stroke, cerebral palsy, spinal cord injury)
- Current urinary tract infection
- History of breast or endometrial cancer
- Use of systemic estrogen therapy in the past 3 months
- Baseline hematocrit \>48%, serum creatinine \>2.5 mg/dL; HbA1c \>8.0%; BMI \>40 kg/m2
- Uncontrolled hypertension defined as an average of two blood pressure readings of greater than 160/100.
- Subjects who are on insulin therapy will be excluded.
- Uncontrolled congestive heart failure
- Myocardial infarction, acute coronary syndrome, revascularization surgery or stroke within 6 months
- History of pulmonary embolism, deep vein thrombosis or a genetic thromboembolic disorder
- History of bipolar disorder, schizophrenia or untreated major depression
- Presence of metallic implants (pacemakers, aneurysm clips, etc.) that preclude the patient from undergoing MRI
