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[177Lu]Ludotadipep Treatment in Patients With Metastatic Castration-resistant Prostate Cancer.

Primary Purpose

Metastatic Castration-resistant Prostate Cancer

Status

Completed

Phase

Phase 1

Locations

Korea, Republic of

Study Type

Interventional

Intervention

[177Lu]Ludotadipep

About this trial

This is an interventional treatment trial for Metastatic Castration-resistant Prostate Cancer focused on measuring Prostate Cancer

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

The Catholic University of Korea, Seoul, St, Mary's Hospital, 222, Banpo-daero, Seocho-gu

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

50mCi

75mCi

100mCi

125mCi

150mCi

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Dose-limiting toxicity

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 Outcome Measures

PSA level assessment

Comparative assessment of the PSA level before and after administration of [177Lu]Ludotadipep

Radiological assessment

Comparative assessment of the locations and the quantitative change of a lesion on [18F]PSMA PET/CT before and after administration of [177Lu]Ludotadipep, and assessment of the treatment response by comparing the intake of the target lesion from an imaging test at each time point.

Biodistribution

Assessment of the absorption (uptake) into the blood, lungs, liver, spleen, pancreas, kidneys, muscle, stomach, and tumor based on the level obtained from SPECT/CT imaging at 2 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days) and additionally perform planar scan at visit 4.

Whole-body absorbed dose

Calculation of the whole-body absorbed dose by evaluating the absorbed dose into the adrenals, brain, gallbladder, intestine, stomach, heart, kidney, liver, muscle, lungs, pancreas, red marrow, skin, spleen, testes, thymus, thyroid, and urinary bladder.

Safety assessment by baseline symptoms

Assessment of adverse events occured from screening (Day -31) and 2nd screening(Day -31 ~ -20) before IP administration.

Safety assessment by adverse events

Assessment of adverse events occured from IP administration (visit 3,Day 0~3) until visit10 (Day87)

Number of participants with abnormal signs and symptom as assessed through physical examination

Number of participants with abnormal signs and symptom as assessed through physical examination from screening(Day -31 ~ -20) to visit10 (Day87)

Systolic and diastolic blood pressure (mm Hg)

Assessment of masured value using systolic and diastolic blood pressure (mm Hg) from screening(Day -31 ~ -20) to visit10 (Day87)

Body temperature (degrees Celsius)

Assessment of masured value using body temperature (degrees Celsius) from screening(Day -31 ~ -20) to visit10 (Day87)

Pulse rate (beats per minute)

Assessment of masured value using pulse rate (beats per minute) from screening(Day -31 ~ -20) to visit10 (Day87)

Number of participants with abnormal hematology values

Number of participants with abnormal hematology values ( WBC, WBC differential, Hemoglobin, Hematocrit, RBC, Platelet, free lutetium -at 3 minutes, 15 minutes, 30 minutes, 60 minutes, 180 minutes, 24 hours, 48 hours, and 72 hours after IP administration) from screening(Day -31 ~ -20) to visit10 (Day87) except 2nd screening(Day -19 ~ -1).

Number of participants with abnormal chemistry values

Assessment of masured value using chemistry( free PSA, glucose, Total bilirubin, AST/ALT, Alkaline phosphatase, BUN/ Creatinine, Sodium, Potassium, Chloride, CA, Phosphorus, Total Protein, Albumin) from screening(Day -31 ~ -20) to visit10 (Day87) except 2nd screening(Day -19 ~ -1).

Number of participants with abnormal urinalysis values

Assessment of masured value using urinalysis (Specific Gravity, Protein, pH, Glucose, Occult Blood, Ketone) from screening(Day -31 ~ -20) to visit10 (Day87) except 2nd screening(Day -19 ~ -1).

Full Information

NCT ID

NCT04509557

First Posted

July 7, 2020

Last Updated

October 19, 2022

Sponsor

FutureChem

1. Study Identification

Unique Protocol Identification Number

NCT04509557

Brief Title

[177Lu]Ludotadipep Treatment in Patients With Metastatic Castration-resistant Prostate Cancer.

Official Title

[177Lu]Ludotadipep Treatment in Patients With Metastatic Castration-resistant Prostate Cancer: Phase I Clinical Trial.

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Completed

Study Start Date

October 14, 2020 (Actual)

Primary Completion Date

June 30, 2022 (Actual)

Study Completion Date

June 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

FutureChem

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Castration-resistant Prostate Cancer

Keywords

Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

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).

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

50mCi

Arm Type

Experimental

Arm Description

Arm Title

75mCi

Arm Type

Experimental

Arm Description

Arm Title

100mCi

Arm Type

Experimental

Arm Description

Arm Title

125mCi

Arm Type

Experimental

Arm Description

Arm Title

150mCi

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

[177Lu]Ludotadipep

Intervention Description

Dose is 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). If DLT is observed in 2 or less of 6 subjects at each level, advance to the next step. If DLT is observed in 3 or more participants, no further subject will participate in the study at the relevant dose. Appropriateness of the dose elevation is evaluated 8-9 weeks after drug administration.

Primary Outcome Measure Information:

Title

Dose-limiting toxicity

Description

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.

Secondary Outcome Measure Information:

Title

PSA level assessment

Description

Comparative assessment of the PSA level before and after administration of [177Lu]Ludotadipep

Time Frame

screening(Day -31 ~ -20), , visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87)

Title

Radiological assessment

Description

Time Frame

2nd screeing(Day -19 ~ -1 ), visit7(Day31), visit9(Day59)

Title

Biodistribution

Description

Time Frame

2 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days) at visit3 (Day 0~3), visit 4(Day10)

Title

Whole-body absorbed dose

Description

Time Frame

2 hours, 24 hours (1 day), 48 hours (2 days), 72 hours (3 days) at visit3(Day 0~3)

Title

Safety assessment by baseline symptoms

Description

Assessment of adverse events occured from screening (Day -31) and 2nd screening(Day -31 ~ -20) before IP administration.

Time Frame

Screening(Day -31 ~ -20), 2nd screening(Day -19 ~ -1)

Title

Safety assessment by adverse events

Description

Assessment of adverse events occured from IP administration (visit 3,Day 0~3) until visit10 (Day87)

Time Frame

visit 3(Day 0 ~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87)

Title

Number of participants with abnormal signs and symptom as assessed through physical examination

Description

Number of participants with abnormal signs and symptom as assessed through physical examination from screening(Day -31 ~ -20) to visit10 (Day87)

Time Frame

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)

Title

Systolic and diastolic blood pressure (mm Hg)

Description

Assessment of masured value using systolic and diastolic blood pressure (mm Hg) from screening(Day -31 ~ -20) to visit10 (Day87)

Time Frame

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)

Title

Body temperature (degrees Celsius)

Description

Assessment of masured value using body temperature (degrees Celsius) from screening(Day -31 ~ -20) to visit10 (Day87)

Time Frame

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)

Title

Pulse rate (beats per minute)

Description

Assessment of masured value using pulse rate (beats per minute) from screening(Day -31 ~ -20) to visit10 (Day87)

Time Frame

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)

Title

Number of participants with abnormal hematology values

Description

Time Frame

Screening(Day -31 ~ -20), visit 3(Day 0~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87)

Title

Number of participants with abnormal chemistry values

Description

Time Frame

Screening(Day -31 ~ -20), visit 3(Day 0~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87)

Title

Number of participants with abnormal urinalysis values

Description

Assessment of masured value using urinalysis (Specific Gravity, Protein, pH, Glucose, Occult Blood, Ketone) from screening(Day -31 ~ -20) to visit10 (Day87) except 2nd screening(Day -19 ~ -1).

Time Frame

Screening(Day -31 ~ -20), visit 3(Day 0~3), visit4 (Day10), visit5 (Day17), visit6(Day24), visit7(Day31), visit8(Day45), visit9(Day59), visit10 (Day87)

10. Eligibility

Sex

Male

Gender Based

Yes

Gender Eligibility Description

Male patients aged 20 years or older.

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ji Youl Lee

Organizational Affiliation

The Catholic University of Korea

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Catholic University of Korea, Seoul, St, Mary's Hospital, 222, Banpo-daero, Seocho-gu

City

Seoul

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

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PubMed Identifier

16341066

Citation

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Citation

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Results Reference

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Citation

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Results Reference

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PubMed Identifier

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Citation

Maurer T, Eiber M, Schwaiger M, Gschwend JE. Current use of PSMA-PET in prostate cancer management. Nat Rev Urol. 2016 Apr;13(4):226-35. doi: 10.1038/nrurol.2016.26. Epub 2016 Feb 23.

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PubMed Identifier

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Citation

Haberkorn U, Eder M, Kopka K, Babich JW, Eisenhut M. New Strategies in Prostate Cancer: Prostate-Specific Membrane Antigen (PSMA) Ligands for Diagnosis and Therapy. Clin Cancer Res. 2016 Jan 1;22(1):9-15. doi: 10.1158/1078-0432.CCR-15-0820.

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[177Lu]Ludotadipep Treatment in Patients With Metastatic Castration-resistant Prostate Cancer.

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