68Ga-PSMA-R2 in Patients With Biochemical Relapse (BR) and Metastatic Prostate Cancer (mPCa)

Prostate Cancer Metastatic Clinical Trial

— PROfind  

Official title:

A Phase 1/2 Open-label, Multi-center, Safety and Tolerability Study of a Single Dose of 68Ga-PSMA-R2 in Patients With Biochemical Relapse (BR) and Metastatic Prostate Cancer (mPCa)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03490032
• Other study ID #: A206D-A01-001
• Secondary ID: CAAA502A12101
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 23, 2018
• Est. completion date: September 13, 2019

Study information

• Verified date: October 2020
• Source: Advanced Accelerator Applications
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was an open-label, multicenter, single dose, Phase I/II study to evaluate the safety and tolerability of a single administration of 3 mega Becquerel (MBq)/kg, but not less than 150 MBq and not more than 250 MBq, of 68^Ga-PSMA-R2 in adult male patients with biochemical relapse (BR) and metastatic prostate cancer (mPCa).

Description:

This study consisted of 2 parts.

• During the first part (Phase I) of the study, 6 subjects with biochemically recurrent prostate cancer (PCa) received the investigational product (IP) and remained at the site for approximately 6 hours post-administration in order to assess the PK, biodistribution versus time, and dosimetry for critical organs. Subjects received a single dose of 3 MBq/kg, (>=150 and =<250 MBq), of 68^Ga-PSMA-R2 intravenously. Serial blood and urine samples were collected for PK characterization and dosimetry and whole-body PET/CT were acquired at selected time points (0 to 4 hours) to determine organ and tumor absorbed doses. Safety assessments were conducted after IP administration on Day 1, and during follow-up on Days 7 and 28.

• In the second part of the study (Phase II), 2 groups of 12 subjects were enrolled (subjects with PCa in biochemical recurrence [PCa-BR], and subjects with prostate cancer in the metastatic stage [mPCa]). Based on the preliminary data analysis from the Phase I part of the study provided sufficient dosimetry data, all subjects underwent the whole body PET/CT imaging optimized for time (up to 2 time points) according to the data analysis from the Phase I part of the study.

This study was comprised of 4 clinical visits and conducted in 3 study periods: screening, administration/imaging, and safety follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: September 13, 2019
• Est. primary completion date: August 20, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males 18 years or older.

2. Signed and dated written informed consent by the subject prior to any study-specific procedures.

3. Histologically confirmed adenocarcinoma of the prostate, defined as follows:

1. Biochemical recurrence: defined as PSA is =0.2 ng/mL after radical prostatectomy or PSA nadir plus 2 ng/mL after radiation therapy with corresponding CT/MRI or bone scan revealing absence of local recurrence or metastatic lesions.

OR

2. Metastatic disease: defined as both, castration-sensitive or castration-resistant mPCa (presence of at least 1 metastatic lymph node, visceral metastasis and/or bone metastasis).

3. At least 2 weeks must have elapsed between last anticancer treatment administration and the administration of the imaging product, 68Ga-PSMA-R2.

4. Prior major surgery must be at least 12 weeks prior to study entry.

5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, with a life expectancy =6 months.

6. Adequate bone marrow reserve and organ function as demonstrated by complete blood count, and biochemistry in blood and urine at Screening:

1. Hemoglobin (Hb): >8 g/dL

2. Platelet count of >50.000/mm3

7. Serum creatinine <1.5*upper limit normal (ULN) or estimated glomerular filtration rate (eGFR) >50 mL/min based upon The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

8. For male subjects with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 28 days after IP administration.

Exclusion Criteria:

1. Pathological finding consistent with small cell, neuroendocrine carcinoma of the prostate or any other histologies different than adenocarcinoma.

2. Administered a radioisotope =<10 physical half-lives prior to the day of PET/CT.

3. Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, or need of indwelling/condom catheters.

4. Uncontrolled pain or incompatibility that results in subject's lack of compliance with imaging procedures.

5. Other known coexisting malignancies except non-melanoma skin or low grade superficial bladder cancer unless definitively treated and proven no evidence of recurrence for 5 years.

6. Subject with known incompatibility to CT scans.

7. Any evidence of severe or uncontrolled systemic or psychiatric diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol, or active infection including human immunodeficiency virus (HIV) and untreated hepatitis B, hepatitis C. Screening for chronic conditions was not required.

8. Subjects who have received any investigational agent within the last 28 days were excluded from participation in this study.

9. Any acute toxicity due to prior chemotherapy and/or radiotherapy that has not resolved according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Studies.

10. Known allergy, hypersensitivity, or intolerance to the IP or its excipients.

11. Subject unlikely to comply with study procedures, restrictions and requirements and judged by the investigator to be unsuitable for study participation.

Related Conditions & MeSH terms

• Prostate Cancer Metastatic
• Prostatic Neoplasms

Intervention

Drug:
• [68Ga]-PSMA-R2
radio-labelled PSMA ligand

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	National Institutes of Health, Warren Grant Magnusen Clinical Center	Bethesda	Maryland
United States	Smilow Cancer Center at Yale New Haven	New Haven	Connecticut
United States	Pheonix Molecular Imaging Center	Phoenix	Arizona
United States	University of California, San Francisco (UCSF)	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Advanced Accelerator Applications

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Emergent Adverse Events	Treatment-emergent adverse events (TEAEs) were collected from first dosing (single administration, Day 1) up to last follow-up visit or until the event has resolved to baseline grade or better or the event was assessed stable by the investigator or the patient was lost to follow-up or withdrew consent. The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.	dosing through 28 days post-dose
Secondary	Phase I: Decay Corrected Tissue Time-activity Curves (TACs) From 68Ga-PSMA-R2 PET/CT Images in Normal Organs	PET/CT scans were performed at approximately 20 to 30 min and at 1, 2, 3 to 4 hours postinjection. Time activity curves (TACs) for various organs (Brain, Heart Wall, Kidney, Lacrimal Gland, Liver, Lungs, Salivary Gland, Spleen and Thyroid) were produced as decay-corrected tissue of injected activity (mSv/MBq) per organ. Only descriptive analysis performed.	68Ga-PSMA-R2 PET imaging acquired at Day 1 (20-30 min post-injection, 1 hour, 2 hours and 3-4 hours post-injection)
Secondary	Phase I: Urinary Excretion of [68Ga]-PSMA-R2	Urine samples were collected (up to 6 hours after dosing) for activity-based pharmacokinetics characterization. The apparent systemic clearance for the analyte in urine (Cl) was summarized with descriptive statistics.	0 to 6 hours post-dose
Secondary	Phase I: Half-life of 68Ga-PSMA-R2 in Blood	Serial blood samples were collected (up to 6 hours after dosing) for activity-based pharmacokinetics characterization. The half-life (T^1/2) for the analyte in blood was summarized with descriptive statistics.	0 to 6 hours post-dose
Secondary	Phase I: Non-decay Corrected Tissue Time-activity Curves (TACs) From 68Ga-PSMA-R2 PET/CT Images in Normal Organs	PET/CT scans were performed at approximately 20 to 30 min and at 1, 2, 3 to 4 hours postinjection. Time activity curves (TACs) for the various organs were produced as non-decay-corrected fraction of injected activity (mSv/MBq) per organ. Only descriptive analysis performed.	68Ga-PSMA-R2 PET imaging acquired at Day 1 (20-30 min post-injection, 1 hour, 2 hours and 3-4 hours post-injection)
Secondary	Phase I: Residence Times in Normal Organs	Residence times of radiation in normal organs were summarized with descriptive statistics.	68Ga-PSMA-R2 PET imaging acquired at Day 1
Secondary	Phase I: Absorbed Dose of 68Ga-PSMA-R2	Absorbed radiation dose of 68Ga-PSMA-R2 in target organs were summarized with descriptive statistics.	68Ga-PSMA-R2 PET imaging acquired at Day 1
Secondary	Phase I: Whole-body Dose of 68Ga-PSMA-R2	The whole-body dose of 68Ga-PSMA-R2 was summarized with descriptive statistics.	68Ga-PSMA-R2 PET imaging acquired at Day 1
Secondary	Phase I: Effective Dose of 68Ga-PSMA-R2	The effective dose of 68Ga-PSMA-R2 was summarized with descriptive statistics.	68Ga-PSMA-R2 PET imaging acquired at Day 1
Secondary	Standard Uptake Value (SUV) Mean and Max in Lesions Detected by PET Scans by Timepoint	Targeting properties of 68Ga-PSMA-R2 were evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET/CT imaging (4 scans). The SUVmean and SUVmax (g/mL) of each lesion were calculated and reported by lesion location with summary statistics at all imaging time points.	68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection)
Secondary	Tumor to Background Ratio (TBR) of Lesions Detected by PET Scans by Timepoint	Targeting properties of 68Ga-PSMA-R2 were evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET/CT imaging (4 scans). The lesion Tumor to Background Ratio (TBR) was defined as SUVmax(lesion) / SUVmean(gluteal or thigh) was calculated and reported by lesion location with summary statistics at all imaging time points.	68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection)
Secondary	Standard Uptake Value (SUV) Mean and Max in Lesions Detected by PET Scans and Also Detected by Conventional Scans by Timepoint	Targeting properties of 68Ga-PSMA-R2 were evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET/CT imaging (4 scans). The SUVmean and SUVmax (g/mL) of each lesion were calculated and reported by lesion location with summary statistics at all imaging time points.	68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection)
Secondary	Tumor to Background Ratio (TBR) of Lesions Detected by PET Scans and Also Detected by Conventional Scans by Timepoint	Targeting properties of 68Ga-PSMA-R2 were evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET/CT imaging (4 scans). The lesion Tumor to Background Ratio (TBR) was defined as SUVmax(lesion) / SUVmean(gluteal or thigh) was calculated and reported by lesion location with summary statistics at all imaging time points.	68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection)
Secondary	Standard Uptake Value (SUV) Mean and Max in Lesions Detected by PET Scans and Not Detected by Conventional Scans by Timepoint	Targeting properties of 68Ga-PSMA-R2 were evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET/CT imaging (4 scans). The SUVmean and SUVmax (g/mL) of each lesion were calculated and reported by lesion location with summary statistics at all imaging time points.	68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection)
Secondary	Tumor to Background Ratio (TBR) of Lesions Detected by PET Scans and Not Detected by Conventional Scans by Timepoint	Targeting properties of 68Ga-PSMA-R2 were evaluated by semi-quantitatively assessing radiotracer uptake at lesion level, identified via PET/CT imaging (4 scans). The lesion Tumor to Background Ratio (TBR) was defined as SUVmax(lesion) / SUVmean(gluteal or thigh) was calculated and reported by lesion location with summary statistics at all imaging time points.	68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection)
Secondary	Patient Level Agreement of 68Ga-PSMA-R2 PET Imaging Relative to Conventional Techniques in Prostate Cancer Patients	The subject-level positive percent agreement, negative percent agreement, and overall percent agreement was calculated based on the number of subjects with at least 1 positive lesion detected by conventional scan or at least 1 positive lesion detected by PET scan. These percent agreements were calculated as follows: Positive percent agreement: a/(a+c) × 100; Negative percent agreement: d/(b+d) × 100; Overall percent agreement: (a+d)/(a+b+c+d) × 100; Where: a = number of subjects with at least 1 positive lesion detected by conventional scan and at least 1 positive lesion detected by PET scan; b = number of subjects with at least 1 positive lesion detected by PET scan that was not correlated with conventional scan; c = number of subjects with at least 1 positive lesion detected by conventional scan that was not correlated with PET scan; d = number of subjects with no lesions detected by conventional scan or PET scan.	68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection)
Secondary	Burden of Tumor Lesions Measured by 68Ga-PSMA-R2 PET (1hr) Scan Compared With Standard Imaging Modality, by Location (Overall)	The differences of number of positive lesions, number of positive lesions detected by PET scan and/or conventional scan and the location of positive lesions were summarized with descriptive statistics.	68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour post-injection)