Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03490032
Recruitment Status : Completed
First Posted : April 6, 2018
Results First Posted : November 17, 2020
Last Update Posted : November 17, 2020
Sponsor:
Information provided by (Responsible Party):
Advanced Accelerator Applications

Brief 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).

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Drug: [68Ga]-PSMA-R2 Phase 1 Phase 2

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Phase I: characterize PK and dosimetry Phase II: diagnostic potential in 2 groups

  1. Prostate Cancer in biochemical relapse, and
  2. Metastatic Prostate Cancer
Masking: None (Open Label)
Primary Purpose: Diagnostic
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)
Actual Study Start Date : May 23, 2018
Actual Primary Completion Date : August 20, 2019
Actual Study Completion Date : September 13, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Biochemically Recurrent Prostate Cancer (PCa-BR) (Phase I)
All eligible participants received recommended dose of [68Ga]-PSMA-R2 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq].
Drug: [68Ga]-PSMA-R2
radio-labelled PSMA ligand

Experimental: Biochemically Recurrent Prostate Cancer (PCa-BR) (Phase II)
All eligible participants received recommended dose of [68Ga]-PSMA-R2 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq].
Drug: [68Ga]-PSMA-R2
radio-labelled PSMA ligand

Experimental: Metastatic Prostate Cancer (mPCa) (Phase II)
All eligible participants received recommended dose of [68Ga]-PSMA-R2 of 3 Mega Becquerel (MBq)/Kg (+/- 10%) [but not more than 250 and not less than 150 MBq].
Drug: [68Ga]-PSMA-R2
radio-labelled PSMA ligand




Primary Outcome Measures :
  1. Number of Participants With Treatment Emergent Adverse Events [ Time Frame: dosing through 28 days post-dose ]
    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.


Secondary Outcome Measures :
  1. Phase I: Decay Corrected Tissue Time-activity Curves (TACs) From 68Ga-PSMA-R2 PET/CT Images in Normal Organs [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 (20-30 min post-injection, 1 hour, 2 hours and 3-4 hours post-injection) ]
    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.

  2. Phase I: Urinary Excretion of [68Ga]-PSMA-R2 [ Time Frame: 0 to 6 hours post-dose ]
    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.

  3. Phase I: Half-life of 68Ga-PSMA-R2 in Blood [ Time Frame: 0 to 6 hours post-dose ]
    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.

  4. Phase I: Non-decay Corrected Tissue Time-activity Curves (TACs) From 68Ga-PSMA-R2 PET/CT Images in Normal Organs [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 (20-30 min post-injection, 1 hour, 2 hours and 3-4 hours post-injection) ]
    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.

  5. Phase I: Residence Times in Normal Organs [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 ]
    Residence times of radiation in normal organs were summarized with descriptive statistics.

  6. Phase I: Absorbed Dose of 68Ga-PSMA-R2 [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 ]
    Absorbed radiation dose of 68Ga-PSMA-R2 in target organs were summarized with descriptive statistics.

  7. Phase I: Whole-body Dose of 68Ga-PSMA-R2 [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 ]
    The whole-body dose of 68Ga-PSMA-R2 was summarized with descriptive statistics.

  8. Phase I: Effective Dose of 68Ga-PSMA-R2 [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 ]
    The effective dose of 68Ga-PSMA-R2 was summarized with descriptive statistics.

  9. Standard Uptake Value (SUV) Mean and Max in Lesions Detected by PET Scans by Timepoint [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection) ]
    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.

  10. Tumor to Background Ratio (TBR) of Lesions Detected by PET Scans by Timepoint [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection) ]
    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.

  11. Standard Uptake Value (SUV) Mean and Max in Lesions Detected by PET Scans and Also Detected by Conventional Scans by Timepoint [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection) ]
    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.

  12. Tumor to Background Ratio (TBR) of Lesions Detected by PET Scans and Also Detected by Conventional Scans by Timepoint [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection) ]
    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.

  13. Standard Uptake Value (SUV) Mean and Max in Lesions Detected by PET Scans and Not Detected by Conventional Scans by Timepoint [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection) ]
    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.

  14. Tumor to Background Ratio (TBR) of Lesions Detected by PET Scans and Not Detected by Conventional Scans by Timepoint [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection) ]
    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.

  15. Patient Level Agreement of 68Ga-PSMA-R2 PET Imaging Relative to Conventional Techniques in Prostate Cancer Patients [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour, 2 hours post-injection) ]

    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.

  16. Burden of Tumor Lesions Measured by 68Ga-PSMA-R2 PET (1hr) Scan Compared With Standard Imaging Modality, by Location (Overall) [ Time Frame: 68Ga-PSMA-R2 PET imaging acquired at Day 1 (1 hour post-injection) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03490032


Locations
Layout table for location information
United States, Arizona
Pheonix Molecular Imaging Center
Phoenix, Arizona, United States, 85040
United States, California
University of California, San Francisco (UCSF)
San Francisco, California, United States, 94158
United States, Connecticut
Smilow Cancer Center at Yale New Haven
New Haven, Connecticut, United States, 06510
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
National Institutes of Health, Warren Grant Magnusen Clinical Center
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Advanced Accelerator Applications
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Advanced Accelerator Applications:
Statistical Analysis Plan  [PDF] June 29, 2020
Study Protocol  [PDF] February 22, 2018

Layout table for additonal information
Responsible Party: Advanced Accelerator Applications
ClinicalTrials.gov Identifier: NCT03490032    
Other Study ID Numbers: A206D-A01-001
CAAA502A12101 ( Other Identifier: Novartis )
First Posted: April 6, 2018    Key Record Dates
Results First Posted: November 17, 2020
Last Update Posted: November 17, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Advanced Accelerator Applications:
Prostatic Neoplasms
Cancer of Prostate
Cancer of the Prostate
Neoplasms, Prostate
Prostate Cancer
Prostatic Cancer
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
PSMA
Prostate-specific membrane antigen
Gallium radioisotope 68
68Ga-PSMA-R2
68Ga-PSMA ligand
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases