Back to resultsA Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, Dosimetry, and Anti-tumor Activity of Ga-68-NGUL / Lu-177-DGUL in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Refractory to Standard Therapy
Primary Purpose
Prostate Cancer, mCRPC
Status
Recruiting
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Lu-177-DGUL
Ga-68-NGUL
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring PSMA
Eligibility Criteria
Inclusion Criteria:
- Male patients of 19 years or older
- Patients with metastatic diseases due to adenocarcinoma of the prostate as confirmed
- Patients whose blood testosterone levels at the screening visit meet the castration criteria(< 50 ng/dL)
- Patients with advanced metastatic castration-resistant prostate cancer who have failed standard treatment or no longer have standard treatment available
- Those who are maintaining androgen deprivation therapy (ADT) regardless of the type
- Patients receiving bone resorption treatment who have maintained a stable dose for at least 4 weeks prior to baseline
- Patients with positive lesions on Ga-68-NGUL PET scan
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Patients with an expected survival of 6months or more
- Patients with confirmed adequate hematological function, renal and hepatic function according to the following criteria
- Patients who have voluntarily consented to participate in this clinical trial and signed the informed consent form
Exclusion Criteria:
- Patients with hematologic malignancy, including lymphoma and solid cancers other than prostate cancer, within 3 years prior to baseline
- Patients who have received chemotherapy, biotherapy, or immunotherapy for prostate cancer treatment within 4 weeks prior to baseline
- Patients who have received radiation chemotherapy or radiation therapy within 12 weeks prior to baseline
- Patients who have received high-dose chemotherapy requiring hematopoietic stem cell therapy within 2 years prior to baseline
- Those who had previously received PSMA-targeted treatment or received radiopharmaceutical treatment, such as radium-223, within 6 months prior to baseline
- Patients with symptomatic central nervous system metastases
- Patients with unsuitable medical history or surgical/procedural history
- Patients with severe drug hypersensitivity and a history of hypersensitivity to the investigational product and similar drugs
- Patients receiving concomitant nephrotoxic drugs
- Patients with severe claustrophobia that is not controlled with anti-anxiety medications
- Patients with hypersensitivity reactions to components of the investigational product
- If the partner is a female of childbearing potential, patients who do not intend to abstain from abstinence or use appropriate contraceptive methods for at least 3 months after the end of the clinical trial period and investigational product administration
- Patients who have been administered with other investigational products or treated with clinical investigational devices within 4 weeks prior to baseline
- Patients who cannot participate in the clinical trial as determined by other investigators
Sites / Locations
- Seoul National University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Phase 1 Part A(Healthy/Disease group)
Phase 1 : Part B(Low dose)
Phase 1 : Part B(High dose)
Phase 2
Arm Description
Subjects are administered intravenously a single dose of 2MBq/kg of Ga-68-NGUL.
Subjects with positive lesions for Ga-68-NGUL are administered intravenously with low dose of Lu-177-DGUL.
Subjects with positive lesions for Ga-68-NGUL are administered intravenously with high dose of Lu-177-DGUL.
Subjects with positive lesions for Ga-68-NGUL are administered intravenously with Lu-177-DGUL with the determined RP2D.
Outcomes
Primary Outcome Measures
Objective Response Rate(ORR) according to RECIST 1.1
ORR is defined as the proportion of participants with best overall response of complete response or partial response according to RECIST 1.1
Secondary Outcome Measures
PSA response rate(> 50% reduction compared to PSA before treatment)
defined as the proportion of subjects who achieved a PSA response, which is considered a reduction of > 50% from baseline prior to treatment
PSA % change
defined as the % change of PSA level compared to baseline.
PSA progression-free survival (PSA PFS)
from the date of first administration of Lu-177-DGUL, the time point at which PSA progression is confirmed or the time point of death is collected, whichever comes first.
Objective Response Rate(ORR) according to mPERCIST
defined as the proportion of participants with best overall response of complete response or partial response according to RECIST 1.1
Best overall response(BOR) according to RECIST 1.1 and mPERCIST criteria
defined as the best response among all responses at each time point from the start date of Lu-177-DGUL administration.
Waterfall plot according to best PSA response
% change in PSA with the highest percentage decrease in PSA values from baseline.
Disease Control Rate(DCR) according to RECIST 1.1 and mPERCIST criteria
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.
Duration of Response(DOR) according to RECIST 1.1 and mPERCIST criteria
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.
PSA Doubling time
defined as the date of doubling time of PSA level from baseline.
Radiological progression-free survival (rPFS)
defined the date of first radiological evaluation of disease progression from the first day of administration of Lu-177-DGUL or the time of death, whichever comes first.
Waterfall plot according to tumor change rate
The size of the target lesion (according to RECIST v1.1) and SUVpeak (according to mPERCIST) % change compared to the baseline are plotted as a waterfall plot
Overall survival (OS)
defined as the date from the first day of administration of Lu-177-DGUL to death
Pain intensity (NRS) and opioid analgesic use
Quality of life (QOL): EORTC QLQ-C30, EORTC QLQ-PR25, EQ-5D-5L
Full Information
NCT ID
NCT05547061
First Posted
September 13, 2022
Last Updated
September 22, 2022
Sponsor
Cellbion Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05547061
Brief Title
A Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, Dosimetry, and Anti-tumor Activity of Ga-68-NGUL / Lu-177-DGUL in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Refractory to Standard Therapy
Official Title
A Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, Dosimetry, and Anti-tumor Activity of Ga-68-NGUL / Lu-177-DGUL in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Refractory to Standard Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 12, 2021 (Actual)
Primary Completion Date
August 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cellbion Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This clinical trial is an open-label, single-arm, single-center, escalation (Phase 1 Part B only), rater-blind (Phase 2 only), phase 1/2 trial to evaluate the diagnostic validity/safety of Ga-68-NGUL and efficacy/safety of Lu-177-DGUL on the anti-tumor activity that aims to simultaneously evaluate diagnostic and therapeutic validity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, mCRPC
Keywords
PSMA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
73 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 Part A(Healthy/Disease group)
Arm Type
Experimental
Arm Description
Subjects are administered intravenously a single dose of 2MBq/kg of Ga-68-NGUL.
Arm Title
Phase 1 : Part B(Low dose)
Arm Type
Experimental
Arm Description
Subjects with positive lesions for Ga-68-NGUL are administered intravenously with low dose of Lu-177-DGUL.
Arm Title
Phase 1 : Part B(High dose)
Arm Type
Experimental
Arm Description
Subjects with positive lesions for Ga-68-NGUL are administered intravenously with high dose of Lu-177-DGUL.
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
Subjects with positive lesions for Ga-68-NGUL are administered intravenously with Lu-177-DGUL with the determined RP2D.
Intervention Type
Drug
Intervention Name(s)
Lu-177-DGUL
Intervention Description
Lu-177-DGUL(150mCi, 200mCi) intravenous 4 doses, 6weeks apart
Intervention Type
Drug
Intervention Name(s)
Ga-68-NGUL
Intervention Description
Ga-68-NGUL(2MBq/kg) intravenous during screening and every 12 weeks after the first administration of Lu-177-DGUL
Primary Outcome Measure Information:
Title
Objective Response Rate(ORR) according to RECIST 1.1
Description
ORR is defined as the proportion of participants with best overall response of complete response or partial response according to RECIST 1.1
Time Frame
From randomization until radiographic progression or death from any cause, whichever comes first. assessed up to 36 months
Secondary Outcome Measure Information:
Title
PSA response rate(> 50% reduction compared to PSA before treatment)
Description
defined as the proportion of subjects who achieved a PSA response, which is considered a reduction of > 50% from baseline prior to treatment
Time Frame
baseline up to 24 weeks
Title
PSA % change
Description
defined as the % change of PSA level compared to baseline.
Time Frame
baseline up to 24 weeks
Title
PSA progression-free survival (PSA PFS)
Description
from the date of first administration of Lu-177-DGUL, the time point at which PSA progression is confirmed or the time point of death is collected, whichever comes first.
Time Frame
From randomization until radiographic progression or death from any cause, whichever comes first. assessed up to 36 months
Title
Objective Response Rate(ORR) according to mPERCIST
Description
defined as the proportion of participants with best overall response of complete response or partial response according to RECIST 1.1
Time Frame
baseline up to 24 weeks
Title
Best overall response(BOR) according to RECIST 1.1 and mPERCIST criteria
Description
defined as the best response among all responses at each time point from the start date of Lu-177-DGUL administration.
Time Frame
baseline up to 24 weeks
Title
Waterfall plot according to best PSA response
Description
% change in PSA with the highest percentage decrease in PSA values from baseline.
Time Frame
baseline up to 24 weeks
Title
Disease Control Rate(DCR) according to RECIST 1.1 and mPERCIST criteria
Description
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
baseline up to 24 weeks
Title
Duration of Response(DOR) according to RECIST 1.1 and mPERCIST criteria
Description
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
From randomization until radiographic progression or death from any cause, whichever comes first. assessed up to 36 months
Title
PSA Doubling time
Description
defined as the date of doubling time of PSA level from baseline.
Time Frame
From randomization until radiographic progression or death from any cause, whichever comes first. assessed up to 36 months
Title
Radiological progression-free survival (rPFS)
Description
defined the date of first radiological evaluation of disease progression from the first day of administration of Lu-177-DGUL or the time of death, whichever comes first.
Time Frame
From randomization until radiographic progression or death from any cause, whichever comes first. assessed up to 36 months
Title
Waterfall plot according to tumor change rate
Description
The size of the target lesion (according to RECIST v1.1) and SUVpeak (according to mPERCIST) % change compared to the baseline are plotted as a waterfall plot
Time Frame
baseline up to 24 weeks
Title
Overall survival (OS)
Description
defined as the date from the first day of administration of Lu-177-DGUL to death
Time Frame
From randomization until radiographic progression or death from any cause, whicheve. assessed up to 36 months.
Title
Pain intensity (NRS) and opioid analgesic use
Time Frame
baseline up to 24 weeks
Title
Quality of life (QOL): EORTC QLQ-C30, EORTC QLQ-PR25, EQ-5D-5L
Time Frame
baseline up to 24 weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male patients of 19 years or older
Patients with metastatic diseases due to adenocarcinoma of the prostate as confirmed
Patients whose blood testosterone levels at the screening visit meet the castration criteria(< 50 ng/dL)
Patients with advanced metastatic castration-resistant prostate cancer who have failed standard treatment or no longer have standard treatment available
Those who are maintaining androgen deprivation therapy (ADT) regardless of the type
Patients receiving bone resorption treatment who have maintained a stable dose for at least 4 weeks prior to baseline
Patients with positive lesions on Ga-68-NGUL PET scan
Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Patients with an expected survival of 6months or more
Patients with confirmed adequate hematological function, renal and hepatic function according to the following criteria
Patients who have voluntarily consented to participate in this clinical trial and signed the informed consent form
Exclusion Criteria:
Patients with hematologic malignancy, including lymphoma and solid cancers other than prostate cancer, within 3 years prior to baseline
Patients who have received chemotherapy, biotherapy, or immunotherapy for prostate cancer treatment within 4 weeks prior to baseline
Patients who have received radiation chemotherapy or radiation therapy within 12 weeks prior to baseline
Patients who have received high-dose chemotherapy requiring hematopoietic stem cell therapy within 2 years prior to baseline
Those who had previously received PSMA-targeted treatment or received radiopharmaceutical treatment, such as radium-223, within 6 months prior to baseline
Patients with symptomatic central nervous system metastases
Patients with unsuitable medical history or surgical/procedural history
Patients with severe drug hypersensitivity and a history of hypersensitivity to the investigational product and similar drugs
Patients receiving concomitant nephrotoxic drugs
Patients with severe claustrophobia that is not controlled with anti-anxiety medications
Patients with hypersensitivity reactions to components of the investigational product
If the partner is a female of childbearing potential, patients who do not intend to abstain from abstinence or use appropriate contraceptive methods for at least 3 months after the end of the clinical trial period and investigational product administration
Patients who have been administered with other investigational products or treated with clinical investigational devices within 4 weeks prior to baseline
Patients who cannot participate in the clinical trial as determined by other investigators
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
bora Jeong
Email
bora.jeong@cellbion.co.kr
First Name & Middle Initial & Last Name or Official Title & Degree
hee jeong SEO
Email
elenaseo@cellbion.co.kr
Facility Information:
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03127
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheol Kwak
12. IPD Sharing Statement
Learn more about this trial
A Phase 1/2 Clinical Trial to Evaluate the Safety, Tolerability, Dosimetry, and Anti-tumor Activity of Ga-68-NGUL / Lu-177-DGUL in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Refractory to Standard Therapy
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