Back to resultsStudy of [177Lu] Lu-XT033 Injection in Patients With Metastatic Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Phase I:[177Lu]Lu-XT033 Injection
Phase II:[177Lu]Lu-XT033 Injection
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate Cancer, [177Lu]Lu-XT033 Injection
Eligibility Criteria
Inclusion Criteria: Patients must have the ability to understand and sign an approved informed consent form (ICF). Patients must be >= 18 and <＝80 years of age. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients must have a life expectancy >6 months. Patients must have histological, pathological, and/or cytological confirmation of prostate cancer. Patients must be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive。 Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L). Patients must have received at least one NAAD (such as enzalutamide and/or abiraterone)； Patients must have been previously treated with at least 1, but no more than 2 previous taxane regimens. Patients must have progressive mCRPC. Patients must have adequate organ function。 Subjects of childbearing potential voluntarily use an effective method of contraception, such as condoms, oral or injectable contraceptives, Intra-uterine device（IUD）,etc., during treatment and within 6 months of the last use of the trial drug. Exclusion Criteria: Previous treatment with any of the following within 6 months of enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed. Known other malignancies. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy within 28 days prior to day of enrollment. Known hypersensitivity to the components of the study therapy or its analogs. A superscan as seen in the baseline bone scan. Patients with a history of Central Nervous System (CNS) metastases. Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or other severe complications.
Sites / Locations
- Peking University Cancer Hospital
- Fudan University Shanghai Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Phase I:[177Lu]Lu-XT033 Injection
Phase II:[177Lu]Lu-XT033 Injection
Arm Description
During dose verification phase,Patients received [177Lu]Lu-XT033 Injection 1.11Gbq（30mCi）/1.85Gbq（50mCi）intravenously every 8 weeks (+/- 1 week) for a maximum of 6 cycles.
During dose expansion phase,patients received [177Lu]Lu-XT033 Injection at R2PD based on phase I.
Outcomes
Primary Outcome Measures
For phase I:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])of [177Lu]Lu-XT033 on dose 1.11Gbq and 1.85Gbq
To evaluate the safety and tolerability of [177Lu]Lu-XT033 Injection assessed from the number and incidence of patients with adverse events using CTCAE v5.0 and physical examination, electrocardiogram and laboratory abnormality, etc
For phase I：Whole body and organ uptake of [177Lu]Lu-XT033 Injection
Quantitate the absorbed radiation doses (expressed as Gy/MBq) of administered [177Lu]Lu-XT033 to kidneys, liver, lungs, spleen, bone/red marrow and salivary glands.
For phase I：Maximum plasma concentration (Cmax) of Lutetium [Lu 177] Lu-XT033 in patients.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
For phase I：Time of observed drug concentration occurrence (Tmax) of Lutetium [Lu 177] Lu-XT033 in patients.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
For phase I：Area Under plasma concentration-time Curve from time 0 to 168 hours (AUC0-168) of Lutetium [Lu 177] Lu-XT033 in patients.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC0-168 will be listed and summarized using descriptive statistics.
For phase II:Prostate-specific Antigen 50 (PSA50) Response
PSA50 response was defined as the proportion of participants who had a >= 50% decrease in PSA from baseline confirmed by a PSA measurement >= 4 weeks later.
Secondary Outcome Measures
For phase I:Prostate-specific Antigen 50 (PSA50) Response
PSA50 response was defined as the proportion of participants who had a >= 50% decrease in PSA from baseline confirmed by a PSA measurement >= 4 weeks later.
For phase I/II:Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level(PCWG3)
Best percentage change from baseline in PSA level was defined as the maximum percent decrease at any time post-baseline.
For phase I/II:Time to PSA progression
PSA progression was defined as: 1) Where a decline from baseline was documented, date that a >= 25% increase in PSA and an absolute increase of 2 ng/mL or more from the nadir was documented and confirmed by a second consecutive value obtained at least 3 weeks later. Rises in PSA within the first 12 weeks of the date of first dose were ignored; 2) Where no decline from baseline was documented, PSA progression was defined as a >= 25% increase from the baseline value along with an increase in absolute value of 2 ng/mL or more after 12 weeks from the date of first dose (without confirmation) as specified in the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines.
For phase I/II:Radiographic Progression-free Survival (rPFS)
Radiographic progression-free survival (rPFS) was defined as the time (in months) from the date of enrollment to the date of radiographic disease progression per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria or death due to any cause.
For phase I/II:Overall Response Rate (ORR)
Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR was based on RECIST 1.1 response for patients with measurable disease at baseline.
For phase I/II: Duration of Response (DOR)
Duration of Response (DOR) was defined as the duration between the date of first documented Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) and the date of first documented radiographic progression or death due to any cause .
For phase I/II:Disease Control Rate (DCR)
Disease control rate (DCR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) according to RECIST v1.1.
For phase I/II:Health related quality of life(HRQOL)
Patient evaluation with questionnaires regarding Quality of Life .
For phase I/II:Time to First Symptomatic Skeletal Event (SSE)
Time to first Symptomatic Skeletal Event (SSE) was defined as the time (in months) from the date of enrollment to the date of the SSE or death from any cause. The SSE date was the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause.
For phase I/II:Overall Survival (OS)
Overall Survival (OS) was defined as the time (in months) from the date of enrollment to the date of death due to any cause. If the patient was not known to have died, then OS was censored. The censoring date was date of the last study visit, or contact, until the cut-off date.
For phase II:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])of [177Lu]Lu-XT033
To evaluate the safety and tolerability of [177Lu]Lu-XT033 Injection assessed from the number and incidence of patients with adverse events using CTCAE v5.0 and physical examination, electrocardiogram and laboratory abnormality, etc
Full Information
NCT ID
NCT06081686
First Posted
August 25, 2023
Last Updated
October 7, 2023
Sponsor
Sinotau Pharmaceutical Group
1. Study Identification
Unique Protocol Identification Number
NCT06081686
Brief Title
Study of [177Lu] Lu-XT033 Injection in Patients With Metastatic Prostate Cancer
Official Title
Phase I/II Study to Evaluate the Safety and Tolerability, Radiation Dosimetry and Pharmacokinetics, and Efficacy of [177Lu] Lu-XT033 Injection in Patients With Metastatic Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sinotau Pharmaceutical Group
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This was a multicenter, open-label, phase I/II study to evaluate the safety and tolerability, radiation dosimetry and pharmacokinetic characteristics, and efficacy of [177Lu] Lu-XT033 injection in patients with metastatic prostate cancer, including a phase I study and a phase II extension study.
Detailed Description
The study for each participant consisted of a Screening period, a Treatment period and a Follow-up period.
In phase I,Six subjects were enrolled in the 1.11 Gbq (30 mCi) group of [177Lu] Lu-XT033 Injection. The last subject in this group completed the 4-week observation period after the first dose, With the consent of the Safety Monitoring Committee (SRC), 6 subjects were enrolled in the 1.85 Gbq (50 mCi) group. Both groups used 8 ± 1 weeks as the dosing interval for a total of 4 doses.In phase II,Subjects who met the inclusion and exclusion criteria were treated with [177Lu] Lu-XT033 injection at the recommended phase II dose（RP2D）.After Cycle 4 treatment and prior to Cycle 5 treatment, the investigator assessed the following criteria to determine whether:
The patient showed evidence of response (i.e. radiological, PSA, clinical benefit)
The patient had signs of residual disease on CT with contrast/MRI or bone scan
The patient had shown good tolerance to the [177Lu] Lu-XT033 Injection
If the patient met all of the criteria above and agreed to continue with additional treatment of [177Lu] Lu-XT033, the Investigator could administer 2 additional cycles. A maximum of 6 cycles of [177Lu] Lu-XT033 as allowed.
All subjects continued to undergo safety, tolerability, and efficacy assessments until the study-specified visit occurred or the subject was lost to follow-up or death whichever came first.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Prostate Cancer, [177Lu]Lu-XT033 Injection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase I:[177Lu]Lu-XT033 Injection
Arm Type
Experimental
Arm Description
During dose verification phase,Patients received [177Lu]Lu-XT033 Injection 1.11Gbq（30mCi）/1.85Gbq（50mCi）intravenously every 8 weeks (+/- 1 week) for a maximum of 6 cycles.
Arm Title
Phase II:[177Lu]Lu-XT033 Injection
Arm Type
Experimental
Arm Description
During dose expansion phase,patients received [177Lu]Lu-XT033 Injection at R2PD based on phase I.
Intervention Type
Drug
Intervention Name(s)
Phase I:[177Lu]Lu-XT033 Injection
Intervention Description
Six subjects were enrolled in the 1.11 Gbq (30 mCi) group of [177Lu] Lu-XT033 Injection. The last subject in this group completed the 4-week observation period after the first dose, With the consent of the Safety Monitoring Committee (SRC), 6 subjects were enrolled in the 1.85 Gbq (50 mCi) group. Both groups used 8 ± 1 weeks as the dosing interval .
Intervention Type
Drug
Intervention Name(s)
Phase II:[177Lu]Lu-XT033 Injection
Intervention Description
Patients received [177Lu]Lu-XT033 Injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles.
Primary Outcome Measure Information:
Title
For phase I:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])of [177Lu]Lu-XT033 on dose 1.11Gbq and 1.85Gbq
Description
To evaluate the safety and tolerability of [177Lu]Lu-XT033 Injection assessed from the number and incidence of patients with adverse events using CTCAE v5.0 and physical examination, electrocardiogram and laboratory abnormality, etc
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase I：Whole body and organ uptake of [177Lu]Lu-XT033 Injection
Description
Quantitate the absorbed radiation doses (expressed as Gy/MBq) of administered [177Lu]Lu-XT033 to kidneys, liver, lungs, spleen, bone/red marrow and salivary glands.
Time Frame
From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
Title
For phase I：Maximum plasma concentration (Cmax) of Lutetium [Lu 177] Lu-XT033 in patients.
Description
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Time Frame
From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
Title
For phase I：Time of observed drug concentration occurrence (Tmax) of Lutetium [Lu 177] Lu-XT033 in patients.
Description
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Time Frame
From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
Title
For phase I：Area Under plasma concentration-time Curve from time 0 to 168 hours (AUC0-168) of Lutetium [Lu 177] Lu-XT033 in patients.
Description
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC0-168 will be listed and summarized using descriptive statistics.
Time Frame
From the first subject enrolled to one week after the last subject completed the first dosing,assessed up to approximately 12 months
Title
For phase II:Prostate-specific Antigen 50 (PSA50) Response
Description
PSA50 response was defined as the proportion of participants who had a >= 50% decrease in PSA from baseline confirmed by a PSA measurement >= 4 weeks later.
Time Frame
Through study completion, assessed up to 2 years.
Secondary Outcome Measure Information:
Title
For phase I:Prostate-specific Antigen 50 (PSA50) Response
Description
PSA50 response was defined as the proportion of participants who had a >= 50% decrease in PSA from baseline confirmed by a PSA measurement >= 4 weeks later.
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase I/II:Best Percentage Change From Baseline in Prostate-specific Antigen (PSA) Level(PCWG3)
Description
Best percentage change from baseline in PSA level was defined as the maximum percent decrease at any time post-baseline.
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase I/II:Time to PSA progression
Description
PSA progression was defined as: 1) Where a decline from baseline was documented, date that a >= 25% increase in PSA and an absolute increase of 2 ng/mL or more from the nadir was documented and confirmed by a second consecutive value obtained at least 3 weeks later. Rises in PSA within the first 12 weeks of the date of first dose were ignored; 2) Where no decline from baseline was documented, PSA progression was defined as a >= 25% increase from the baseline value along with an increase in absolute value of 2 ng/mL or more after 12 weeks from the date of first dose (without confirmation) as specified in the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines.
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase I/II:Radiographic Progression-free Survival (rPFS)
Description
Radiographic progression-free survival (rPFS) was defined as the time (in months) from the date of enrollment to the date of radiographic disease progression per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria or death due to any cause.
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase I/II:Overall Response Rate (ORR)
Description
Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR was based on RECIST 1.1 response for patients with measurable disease at baseline.
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase I/II: Duration of Response (DOR)
Description
Duration of Response (DOR) was defined as the duration between the date of first documented Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) and the date of first documented radiographic progression or death due to any cause .
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase I/II:Disease Control Rate (DCR)
Description
Disease control rate (DCR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) according to RECIST v1.1.
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase I/II:Health related quality of life(HRQOL)
Description
Patient evaluation with questionnaires regarding Quality of Life .
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase I/II:Time to First Symptomatic Skeletal Event (SSE)
Description
Time to first Symptomatic Skeletal Event (SSE) was defined as the time (in months) from the date of enrollment to the date of the SSE or death from any cause. The SSE date was the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause.
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase I/II:Overall Survival (OS)
Description
Overall Survival (OS) was defined as the time (in months) from the date of enrollment to the date of death due to any cause. If the patient was not known to have died, then OS was censored. The censoring date was date of the last study visit, or contact, until the cut-off date.
Time Frame
Through study completion, assessed up to 2 years.
Title
For phase II:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])of [177Lu]Lu-XT033
Description
To evaluate the safety and tolerability of [177Lu]Lu-XT033 Injection assessed from the number and incidence of patients with adverse events using CTCAE v5.0 and physical examination, electrocardiogram and laboratory abnormality, etc
Time Frame
Through study completion, assessed up to 2 years.
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have the ability to understand and sign an approved informed consent form (ICF).
Patients must be >= 18 and <＝80 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Patients must have a life expectancy >6 months.
Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.
Patients must be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive。
Patients must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L).
Patients must have received at least one NAAD (such as enzalutamide and/or abiraterone)； Patients must have been previously treated with at least 1, but no more than 2 previous taxane regimens.
Patients must have progressive mCRPC.
Patients must have adequate organ function。
Subjects of childbearing potential voluntarily use an effective method of contraception, such as condoms, oral or injectable contraceptives, Intra-uterine device（IUD）,etc., during treatment and within 6 months of the last use of the trial drug.
Exclusion Criteria:
Previous treatment with any of the following within 6 months of enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed.
Known other malignancies.
Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy within 28 days prior to day of enrollment.
Known hypersensitivity to the components of the study therapy or its analogs.
A superscan as seen in the baseline bone scan.
Patients with a history of Central Nervous System (CNS) metastases.
Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, or other severe complications.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shan Zhang
Phone
010-52805710
Email
zhangshan@sinotau.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dingwei Ye
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Zhi Yang
Organizational Affiliation
Peking University Cancer Hospital & Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University Cancer Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100042
Country
China
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
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Study of [177Lu] Lu-XT033 Injection in Patients With Metastatic Prostate Cancer
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