[177Lu]Ludotadipep Treatment in Patients With Metastatic Castration-resistant Prostate Cancer: Phase I Clinical Trial.
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Dose-limiting toxicity
Study Overview
Brief Summary
The study aims to evaluate the stability and efficacy after administration of [177Lu]Ludotadipep in patients with metastatic castration resistant prostate cancer (mCRPC), with dose-escalation applied to determine the appropriate dose.
Detailed Description
[18F]PSMA PET/CT is conducted at the 2nd screening and only PSMA PET/CT positive patients can be enrolled (PSMA RADS 4 or more).
Dose is administered by differentiated into 5 groups (6 subjects each) and sequentially elevated starting from a low dose to a high dose (50±5 mCi, 75±8 mCi, 100±10 mCi, 125±13 mCi, 150±15 mCi).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Among prostate cancer patients with blood testosterone ≤50ng/dL, mCRPC patients showing radiological progression after standard taxene-based anticancer treatment and 2nd generation hormone agent (abiraterone, enzalutamed, or both)) treatment or patients who are not eligible for such standard medical treatment at the discretion of an investigator or patients who refuse such standard treatment
- •Patients who are positive on the [18F]PSMA PET/CT imaging
- •Subjects who were fully informed by an investigator of the study objectives, details, and characteristics of the study drug prior to study enrollment, and had an informed consent form signed by the subject or caretaker or legally acceptable representative
- •Male patients aged 20 years or older
- •Subjects who are sexually active and have a female partner of childbearing potential should meet the followings
- •Subjects should consent to practice contraception by continuously using a male condom from screening, throughout the study, and for at least 6 months after the last dose of the study drug
- •Subjects should never donate sperms from screening, throughout the study, and for at least 6 months after the last dose of the study drug
- •Subjects with a partner who is a woman of childbearing potential (including a pregnant or breastfeeding mother) should consent to maintain sexual abstinence or practice double contraception throughout the study * Double contraception: Corresponding to 2 or more of the followings - use of a condom, use of a non-hormonal intrauterine device, use of a diaphragm, use of a cervical cap, a sexual partner who has been vasectomized at least 3 months (as of the first screening visit) or a sexual partner medically diagnosed to be sterile
- •ECOG _ Performance score ≤2
- •Life expectancy ≥6 months
Exclusion Criteria
- •Subjects determined by an investigator to have a serious medical condition making study conduct difficult
- •Subjects corresponding to the following conditions 1) Glomerular filtration rate ≤40 ml/min, 2) hemoglobin level ≤10.0 g/dL, 3) white cell count ≤4.0 × 109/L, 4) platelet count ≤100 × 109/L, 5) total bilirubin level ≥1.5 x upper normal limit, 6) serum albumin level ≤3.0 g/dL, 7) active ischemic heart disease or heart failure (New York Heart Association Classification III-IV), 8) uncontrolled diabetes/hypertension, 9) hyperkalemia >6.0 mmol/L
- •Vulnerable subjects (the investigator involved in the study or his/her family, research staff or students of the investigator involved in the study)
- •Patients with a persistent malignancy other than the prostate cancer
- •Patients who participated in a therapeutic clinical trial within the past 30 days and administered an investigational product other than standard treatment
- •Patients are excluded if treatment other than the treatment provided in this study is determined more appropriate as determined by the investigator based on the patient and disease characteristics
Arms & Interventions
50mCi
Using a drug product for which dose is determined (50±5 mCi dose), dilute with 0.9% NaCl 5 mL and slowly i.v. inject over 10 minutes, with 500 mL of 0.9% NaCl slowly administered for hydration over approximately 90 minutes from 30 minutes before treatment to 60 minutes after treatment.
Intervention: [177Lu]Ludotadipep (Drug)
75mCi
Using a drug product for which dose is determined (75±8 mCi dose), dilute with 0.9% NaCl 5 mL and slowly i.v. inject over 10 minutes, with 500 mL of 0.9% NaCl slowly administered for hydration over approximately 90 minutes from 30 minutes before treatment to 60 minutes after treatment.
Intervention: [177Lu]Ludotadipep (Drug)
100mCi
Using a drug product for which dose is determined (100±10 mCi dose), dilute with 0.9% NaCl 5 mL and slowly i.v. inject over 10 minutes, with 500 mL of 0.9% NaCl slowly administered for hydration over approximately 90 minutes from 30 minutes before treatment to 60 minutes after treatment.
Intervention: [177Lu]Ludotadipep (Drug)
125mCi
Using a drug product for which dose is determined (125±13 mCi dose), dilute with 0.9% NaCl 5 mL and slowly i.v. inject over 10 minutes, with 500 mL of 0.9% NaCl slowly administered for hydration over approximately 90 minutes from 30 minutes before treatment to 60 minutes after treatment.
Intervention: [177Lu]Ludotadipep (Drug)
150mCi
Using a drug product for which dose is determined (150±15 mCi dose), dilute with 0.9% NaCl 5 mL and slowly i.v. inject over 10 minutes, with 500 mL of 0.9% NaCl slowly administered for hydration over approximately 90 minutes from 30 minutes before treatment to 60 minutes after treatment.
Intervention: [177Lu]Ludotadipep (Drug)
Outcomes
Primary Outcomes
Dose-limiting toxicity
Time Frame: From date of randomization (IP administration (0h, visit3, Day 0 ~ 3)) until the date of grade 4 neutropenia, grade 3 febrile neutropenia, other grade 3 or 4 non-hematological toxicity resulting from [177Lu]Ludotadipep, persisting for 5 days or more.
Dose-limiting toxicity is defined as CTCAE grade 4 thrombocytopenia (platelet count \<25x109/L), grade 4 neutropenia (absolute neutrophil count (ANC) \< 0.5 x 109), grade 3 febrile neutropenia (ANC \<1000/mm3 and temperature \>38.3℃ on at least 1 occasion or temperature ≥38℃ persisting for 1 hr), and other grade 3 or 4 non-hematological toxicity resulting from \[177Lu\]Ludotadipep, persisting for 5 days or more.
Secondary Outcomes
- Whole-body absorbed dose(2 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days) at visit3(Day 0~3))
- Safety assessment by baseline symptoms(Screening(Day -31 ~ -20), 2nd screening(Day -19 ~ -1))
- Biodistribution(2 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days) at visit3 (Day 0~3), visit 4(Day10))
- Number of participants with abnormal signs and symptom as assessed through physical examination(Screening(Day -31 ~ -20), 2nd screening(Day -19 ~ -1), visit 3(Day 0~3), visit4 (Day 10), visit5 (Day 17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87))
- Body temperature (degrees Celsius)(Screening(Day -31 ~ -20), 2nd screening(Day -19 ~ -1), visit 3(Day 0~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87))
- PSA level assessment(screening(Day -31 ~ -20), , visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87))
- Radiological assessment(2nd screeing(Day -19 ~ -1 ), visit7(Day31), visit9(Day59))
- Number of participants with abnormal chemistry values(Screening(Day -31 ~ -20), visit 3(Day 0~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87))
- Systolic and diastolic blood pressure (mm Hg)(Screening(Day -31 ~ -20), 2nd screening(Day -19 ~ -1), visit 3(Day 0~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87))
- Number of participants with abnormal urinalysis values(Screening(Day -31 ~ -20), visit 3(Day 0~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87))
- Safety assessment by adverse events(visit 3(Day 0 ~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87))
- Pulse rate (beats per minute)(Screening(Day -31 ~ -20), 2nd screening(Day -19 ~ -1), visit 3(Day 0~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87))
- Number of participants with abnormal hematology values(Screening(Day -31 ~ -20), visit 3(Day 0~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87))