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177Lu-PSMA-R2 in Patients With PSMA Positive Progressive, Metastatic, Castration Resistant Prostate Cancer (PROter)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03490838
Recruitment Status : Recruiting
First Posted : April 6, 2018
Last Update Posted : April 11, 2019
Information provided by (Responsible Party):
Advanced Accelerator Applications

Brief Summary:
This Phase 1/2 study is intended to investigate the safety, tolerability, and radiation dosimetry of 177Lu-PSMA-R2 and further assess preliminary efficacy data in patients with metastatic castration-resistant prostate cancer (mCRPC). The Phase 1 portion of the study will determine the recommended dose of 177Lu-PSMA-R2 for radio-ligand therapy (RLT) of mCRPC, and the Phase 2 portion will expand into approximately 60 patients documenting the preliminary activity (anti-tumor response) of repeated treatments administered, continuing safety assessments and collecting QoL data.

Condition or disease Intervention/treatment Phase
Prostatic Neoplasm Drug: 177Lu-PSMA-R2 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1 dose escalation: patients enrolled in parallel to one of three dose groups Phase 2 dose expansion: single group, enrolled after Phase 1 dose escalation completed
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-label, Multi-center, Dose-escalation Study of Safety, Tolerability, Pharmacokinetics, Dosimetry, and Response to Repeat Dosing of 177Lu-PSMA-R2 Radio-ligand Therapy in Patients With Prostate Specific Membrane Antigen (PSMA) Positive (68Ga-PSMA-R2) Progressive Metastatic Castration-resistant Prostate Cancer, Following Previous Systemic Treatment
Actual Study Start Date : May 24, 2018
Estimated Primary Completion Date : June 24, 2022
Estimated Study Completion Date : June 24, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Phase I: Dose Escalation Cohort 1
3.70 GBq (100 mCi) x 3 times = 11.10 GBq
Drug: 177Lu-PSMA-R2
radio-ligand therapy

Experimental: Phase I: Dose Escalation Cohort 2
7.40 GBq (200 mCi) x 3 times = 22.2 GBq
Drug: 177Lu-PSMA-R2
radio-ligand therapy

Experimental: Phase I: Dose Escalation Cohort 3
9.25 GBq (250 mCi) x 3 times = 27.75 GBq
Drug: 177Lu-PSMA-R2
radio-ligand therapy

Experimental: Phase II: Dose Expansion Cohort
Dose to be chosen from Phase I
Drug: 177Lu-PSMA-R2
radio-ligand therapy

Primary Outcome Measures :
  1. Phase 1: Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: dosing through 5-years post-treatment ]
  2. Phase 1: Maximum Tolerated Dose (MTD) [ Time Frame: Days 1 through 8 post-treatment ]
  3. Phase 1: Dose Limiting Toxicity (DLT) [ Time Frame: Days 1 through 8 post-treatment ]
  4. Phase 1: Characterization of Recommended Phase 2 Dose [ Time Frame: Days 1 through 8 post-treatment ]
  5. Phase 1: Biodistribution [ Time Frame: Days 1 through 8 post-treatment ]
  6. Phase 1: Pharmacokinetic Profile - systemic exposure [ Time Frame: Days 1 through 8 post-treatment ]
  7. Phase 1: Pharmacokinetic Profile - clearance [ Time Frame: Days 1 through 8 post-treatment ]
  8. Phase 1: Pharmacokinetic Profile - volume of distribution [ Time Frame: Days 1 through 8 post-treatment ]
  9. Phase 1: Pharmacokinetic Profile - terminal half life [ Time Frame: Days 1 through 8 post-treatment ]
  10. Phase 1: Radiation Dosimetry [ Time Frame: Days 1 through 8 post-treatment ]
  11. Phase 2: radiographic progression-free survival (rPFS) per PCa working group 3 (PCWG3) [ Time Frame: up to 5 years post-treatment ]

Secondary Outcome Measures :
  1. Phase 1: PSA response [ Time Frame: weeks 7, 13, and 19 and up to 5 years post-treatment ]
  2. Phase 1: Time to PSA progression [ Time Frame: 5 years post-treatment ]
  3. Phase 1: rPFS per PCWG3 [ Time Frame: 5 years post-treatment ]
  4. Phase 1: Overall Survival (OS) [ Time Frame: 5 years post-treatment ]
  5. Phase 2: Treatment-Emergent Adverse Events [ Time Frame: dosing up to 5 years post-treatment ]
  6. Phase 2: PSA response [ Time Frame: weeks 7, 13, 19 and up to 5 years post-treatment ]
  7. Phase 2: Time to PSA progression [ Time Frame: 5 years post-treatment ]
  8. Phase 2: Overall Survival [ Time Frame: 5 years post-treatment ]

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.

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

Inclusion Criteria:

  • Male patients, 18 years of age or older
  • Signed and dated written ICF by the patient or legally acceptable representative prior to any study-specific procedures
  • Histologically confirmed adenocarcinoma of the prostate
  • Serum testosterone levels < 50 ng/L after surgical or continued chemical castration
  • Metastatic disease documented by CT/MRI or bone scan (not older than 28 days at enrollment) revealing at least one metastatic lymph-node, visceral metastasis and/or bone metastasis
  • Positive 68Ga-PSMA-R2 PET/CT scan for central eligibility assessment. Patients who receive 68Ga-PSMA-R2 as part of separate clinical protocol are eligible (must meet all study eligibility criteria)
  • Documented disease progression on or after prior systemic treatment administered for the advanced disease including CYP 17 inhibitors and/or androgen-pathway inhibitors (i.e. abiraterone and/or enzalutamide when available) and no more than one line of chemotherapy for the advanced disease, or patients who were ineligible (unfit) to receive chemotherapy. Disease progression defined as increasing serum PSA (per PCWG3), radiological progression or ≥ 2 new bone lesions. (Chemical castration is required unless surgically orchiectomized.)
  • At least 28 days elapsed between last anti-cancer treatment administration and the initiation of study treatment (except for Luteinizing Hormone-releasing Hormone [LHRH] or Gonadotropin-releasing Hormone [GnRH]), or resolution of all previous treatment related toxicities to CTCAE version 4.03 grade of ≤ 1 (except for chemotherapy induced alopecia and grade 2 peripheral neuropathy or grade 2 urinary frequency which are allowed). Prior major surgery must be at least 12 weeks prior to study entry.
  • Eastern cooperative oncology group (ECOG) performance status of 0-2 with a life expectancy ≥ 6 months
  • Adequate bone marrow reserve and organ function as demonstrated by complete blood count, and biochemistry in blood and urine at baseline

    1. Platelet count of >100 x109/L
    2. White blood cell (WBC) count 3,000/mL
    3. Neutrophil count of > 1,500/mL
    4. Hemoglobin ≥ 10 g/dL
    5. Serum creatinine < 1.5 x upper limit normal (ULN) or estimated glomerular filtration rate (GFR) > 50 mL/min based upon Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Patients with estimated GFR between 50 - 60 mL/min at baseline will require a 99mTc-DTPA GFR test and only patients with non-obstructive pathology will be included in the study.
    6. Total bilirubin < 3 x ULN (except if confirmed history of Gilbert's disease)
    7. Baseline serum albumin > 30 g/L
    8. Aspartate aminotransferase (AST) < 3 times the ULN
  • For male patients with partners of childbearing potential, agreement to use barrier contraceptive method (condom) and to continue its use for 6 months from receiving the last dose of IP

Exclusion Criteria:

  • Pathological finding consistent with small cell, neuroendocrine carcinoma of the prostate or any other histology different than adenocarcinoma
  • Previously administered chemotherapy or 223Ra-therapy within the context of diffuse bone or bone-marrow involvement (i.e. "superscan" defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake [>20 bone lesions] in relation to soft tissues along with absent or faint activity in the genitourinary tract due to diffuse bone/ bone marrow metastases)
  • Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters
  • Spinal cord compression or brain metastases
  • Uncontrolled pain that results in patient's lack of compliance with the imaging procedures
  • Uncontrolled cardiovascular history, defined as:

    • Congestive heart failure (New York Heart Association [NYHA] II, III, IV)
    • Mean resting corrected QT interval (QTc) >450 millisecond (msec), obtained from 3 ECGs recordings, using the screening clinic ECG machine-derived QTc value.
    • Any clinically relevant abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250 msec).
    • Any factor increasing the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives, or any concomitant medication known to prolong the QT interval.
  • Other known co-existing malignancies except non-melanoma skin cancer unless definitively treated and proven no evidence of recurrence for 5 years.
  • History of deep vein thrombosis and/or pulmonary embolism within 4 weeks of enrollment.
  • Known incompatibility to CT or PET scans.
  • 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 patient to participate in the trial or which would jeopardize compliance with the protocol
  • Active infection including human immunodeficiency virus (HIV) and untreated hepatitis B, and hepatitis C. Screening for chronic conditions is not required.
  • Patients who have received any investigational treatment agent within the last 28 days.
  • Known allergies, hypersensitivity, or intolerance to the IP or its excipients
  • Known history of myelodysplastic syndrome/leukemia at any time
  • Patient is unlikely to comply with study procedures, restrictions and requirements and judged by the Investigator that the patient is not suitable for participation in the study.

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 identifier (NCT number): NCT03490838

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Contact: Sally Parascandola 212-430-2231

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United States, Arizona
Pheonix Molecular Imaging Center Active, not recruiting
Phoenix, Arizona, United States, 85040
United States, California
Stanford Hospital and Clinics Recruiting
Palo Alto, California, United States, 94305
Contact: Andrei Iagaru         
United States, Connecticut
Yale University, Smilow Cancer Hospital Recruiting
New Haven, Connecticut, United States, 06520
Contact: Daniel Petrylak, MD         
United States, Louisiana
Tulane Medical Center Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Alton Sartor         
United States, Wisconsin
University of Wisconsin Clinical Science Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Steve Cho, MD         
Sponsors and Collaborators
Advanced Accelerator Applications
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Study Director: Darhsan Dalal, MD Advanced Accelerator Applications

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Responsible Party: Advanced Accelerator Applications Identifier: NCT03490838     History of Changes
Other Study ID Numbers: A206T-G01-001
First Posted: April 6, 2018    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases