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Phase I Dose-escalation Study of Fractionated 177Lu-PSMA-617 for Progressive Metastatic CRPC

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ClinicalTrials.gov Identifier: NCT03042468
Recruitment Status : Recruiting
First Posted : February 3, 2017
Last Update Posted : August 3, 2020
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:
The purpose of this study is to find the highest dose level of the study drug, 177Lu-PSMA-617 that can be given without severe side effects for advanced prostate cancer.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: 177Lu-PSMA-617 Drug: 68Ga-PSMA-HBED-CC Phase 1 Phase 2

Detailed Description:

Phase I dose escalation study with 177Lu-PSMA-617 using dose fractionation regimen will be performed in patients with documented progressive metastatic CRPC. The cumulative 177Lu dose [100 mCi (3.7 GBq) - 600 mCi (22.2 GBq)] will be escalated in up to 6 different dose levels (3 + 3 study design). Additional 10 subjects will be enrolled at the MTD dose level to further assess safety and tolerability and to obtain a preliminary assessment of efficacy. The study will enroll adult males 18 years of age or older with documented progressive metastatic CRPC. The primary objectives are: - To determine the dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 - To determine the maximal tolerated and recommended phase II dose of 177Lu-PSMA-617 in a 2-week dose-fractionation regimen Subjects will receive the following study interventions:

  1. 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)
  2. 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging Subjects will be on this study from screening to end of study (day 85).

The treatment phase comprises of 8 visits over 12 weeks. Patients will be followed until death for survival assessment. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event. All tests and procedures performed on this study are routine and standard of care except: 68Ga-PSMA-HBED-CC PET/CT scan, administration of investigational agent 177Lu-PSMA-617, research blood samples (CTCs for research, cell-free DNA sample), and PSMA testing on archive tissue.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/ll Dose-escalation Study of Fractionated Dose 177Lu-PSMA-617 for Progressive Metastatic Castration Resistant Prostate Cancer
Study Start Date : December 2016
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: All subjects
  1. 177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)
  2. 68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging
Drug: 177Lu-PSMA-617
177Lu-PSMA-617 [50mCi (1.85GBq) - 300mCi (11.1GBq)] intravenous X2 doses, 2 weeks apart (Visit 1 and 2)

Drug: 68Ga-PSMA-HBED-CC
68Ga-PSMA-HBED-CC [5 ±2mCi or 185 ±74MBq] intravenous during screening and at 12 weeks with standard imaging




Primary Outcome Measures :
  1. Proportion of subjects with dose limiting toxicity (DLT) of fractionated dose of 177Lu-PSMA-617 by using 3+3 dose escalation will be used. [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  2. Cumulative maximum tolerated dose (MTD) and recommended phase II dose of 177Lu-PSMA-617 in a 2-wk dose-fractionation regimen by using a 3+3 dose escalation design [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]

Secondary Outcome Measures :
  1. The rate of PSA decline following fractionated 177Lu-PSMA-617, PSA response will be determined by comparing the PSA levels after therapy to the baseline, pre-treatment PSA. [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  2. Radiographic response rate measured by RECIST 1.1 with PCWG3 modifications [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  3. Radiographic progression-free survival measured by PCWG3 criteria [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  4. Changes in CTC count as measured by CellSearch and the rate of favorable CTC count and LDH at 12 weeks following fractionated 177Lu-PSMA-617 [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  5. Whole body distribution of 177Lu-PSMA-617 by performing planar/SPECT imaging of 177Lu-PSMA-617 at post-treatment follow up [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  6. Radiation dosimetry of 177Lu-PSMA-617 and correlate toxicity with radiation dosimetry by performing planar/SPECT imaging of 177Lu-PSMA-617 at post-treatment follow up [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  7. Change in Biochemical and radiographic progression-free survival (PFS) as measured by bone scan [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  8. Overall survival following fractionated 177Lu-PSMA-617 [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  9. Change in Biochemical and radiographic progression-free survival (PFS) as measured by Chest x-ray (CXR waived if CT/MRI includes chest) [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  10. Change in Biochemical and radiographic progression-free survival (PFS) as measured by CT/MRI of abdomen/pelvis [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  11. Change in adverse event rate response [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]

Other Outcome Measures:
  1. Disease assessment with 68Ga-PSMA-HBED-CC PET/CT prior to and following investigational treatment [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  2. Semi-quantitative PSMA expression on Circulating Tumor Cells will be collected [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  3. Genomic DNA repair pathways in relationship to outcome following fractionated dose 177Lu-PSMA-617 by collecting archival pathology tissue. [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  4. Patient reported outcomes using the Brief Pain Inventory [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]
  5. Patient reported outcomes using Functional Assessment Cancer Therapy-Prostate [ Time Frame: at least 12 weeks of subsequent follow-up evaluations ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed adenocarcinoma of prostate
  2. Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria:

    • PSA progression
    • Objective radiographic progression in soft tissue
    • New bone lesions
  3. ECOG performance status of 0-2
  4. Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy.
  5. Have previously been treated with at least one of the following:

    • Androgen receptor signaling inhibitor (such as enzalutamide)
    • CYP 17 inhibitor (such as abiraterone acetate)
  6. Have previously received taxane chemotherapy, been determined to be ineligible for taxane chemotherapy by their physician, or refused taxane chemotherapy.
  7. Age > 18 years
  8. Patients must have normal organ and marrow function as defined below:

    • Absolute neutrophil count >2,000 cells/mm3
    • Hemoglobin ≥9 g/dL (independent of transfusion and/or growth factors within 1 month prior to registration)
    • Platelet count >150,000 x 109/uL (independent of transfusion and/or growth factors within 3 months prior to randomization)
    • Serum creatinine <1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
    • Serum total bilirubin <1.5 x ULN (unless due to Gilbert's syndrome in which case direct bilirubin must be normal
    • Serum AST and ALT <1.5 x ULN
  9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Use of investigational drugs or implantation of investigational medical device ≤4 weeks of Cycle 1, Day 1 or current enrollment in investigational drug or device study
  2. Prior systemic beta-emitting bone-seeking radioisotopes
  3. Brain metastases or leptomeningeal disease
  4. History of deep vein thrombosis and/or pulmonary embolus within 1 month of study entry
  5. Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study
  6. Radiation therapy for treatment of PCa ≤4 weeks of Day 1 Cycle 1
  7. Patients on stable dose of bisphosphonates or denosumab, which have been started no less than 4 weeks prior to treatment start, may continue on this medication, however patients are not allowed to initiate bisphosphonate/Denosumab therapy during the DLT-assessment period of the study.
  8. Having partners of childbearing potential and not willing to use a method of birth control deemed acceptable by the principle investigator and chairperson during the study and for 1 month after last study drug administration
  9. Currently active other malignancy other than non-melanoma skin cancer. Patients are considered not to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.
  10. Known history of known myelodysplastic syndrome

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): NCT03042468


Contacts
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Contact: GUONC Research Team guonc@med.cornell.edu

Locations
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United States, Louisiana
Tulane Cancer Center Clinic Not yet recruiting
New Orleans, Louisiana, United States, 70112
Contact: Patrick Cotogno    504-988-6542    pcotogno@tulane.edu   
Principal Investigator: Alton Sartor, MD         
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10021
Contact: GUONC Research Team       guonc@med.cornell.edu   
Principal Investigator: Scott T Tagawa, M.D.         
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
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Principal Investigator: Scott Tagawa, MD Weill Cornell Medicine
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Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT03042468    
Other Study ID Numbers: 1609017542
PSMA-617 ( Other Identifier: Weill Cornell Medical College )
First Posted: February 3, 2017    Key Record Dates
Last Update Posted: August 3, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Neoplasms
Prostatic Diseases