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Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer (VISION)

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ClinicalTrials.gov Identifier: NCT03511664
Recruitment Status : Recruiting
First Posted : April 30, 2018
Last Update Posted : July 24, 2019
Sponsor:
Information provided by (Responsible Party):
Endocyte

Tracking Information
First Submitted Date  ICMJE April 13, 2018
First Posted Date  ICMJE April 30, 2018
Last Update Posted Date July 24, 2019
Actual Study Start Date  ICMJE May 23, 2018
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2018)
Overall Survival [ Time Frame: Every 6-8 weeks until end of treatment and every 3 months during long term follow up [up to 24 months ]
Overall survival (OS) in patients with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/standard of care
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03511664 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer
Official Title  ICMJE VISION: An International, Prospective, Open Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 in the Treatment of Patients With Progressive PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC)
Brief Summary

The primary objective of this study is to compare overall survival (OS) in patients with progressive PSMA-positive mCRPC who receive 177Lu-PSMA-617 in addition to best supportive/best standard of care versus patients treated with best supportive/best standard of care alone.

Key secondary objectives are an arm-to-arm comparison of the following:

  • Radiographic progression-free survival (rPFS)
  • Response Evaluation Criteria in Solid Tumors (RECIST) response
  • Time to a first symptomatic skeletal event (SSE)

Additional Secondary Objectives:

  • Safety and tolerability of 177Lu-PSMA-617
  • Health-related quality of life (HRQoL; EQ-5D-5L, FACT-P and Brief Pain Inventory - Short Form (BPI-SF))
  • Health economics
  • Progression-free survival (PFS) (radiographic, clinical, or prostate-specific antigen [PSA] progression-free survival)
  • Biochemical response as measured by PSA. Alkaline phosphatase [ALP] levels and lactate dehydrogenase [LDH] levels will also be measured.
Detailed Description

Patients with PSMA positive scans will be randomized in a 2:1 ratio to receive either 177Lu-PSMA-617 plus best supportive/best standard of care or to receive best supportive/best standard of care only. Best supportive/best standard of care will be determined by the treating physician/investigator but will exclude investigational agents, cytotoxic chemotherapy, other systemic radioisotopes, and hemi-body radiotherapy. Novel androgen axis drugs [NAADs] (such as abiraterone or enzalutamide) are allowed.

The study is open-label and patients will be monitored throughout the 6 to 10-month treatment period for survival, disease progression, and adverse events.

A long-term follow-up period will include the collection of survival and treatment updates, adverse events assessment, as well as blood for hematology and chemistry testing. During follow-up, patients will be contacted every 3 months (±1 month) via phone, email, or letter for 24 months or until the the overall censoring rate for survival reduces to a level identified in the SAP.

An End of Treatment visit should occur once a patient is to enter the long term follow up. This visit should occur approximately 30 days from the last dose of 177Lu-PSMA-617 or best supportive/best standard of care, but before the initiation of subsequent anti-cancer treatment, outside of what is allowed on study.

The planned enrollment for this study is 750 patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The study population includes patients with progressive PSMA-positive mCRPC who received at least one novel androgen axis drug [NAAD] (such as enzalutamide or abiraterone) and were previously treated with 1 to 2 taxane regimens. Patients treated with only 1 prior taxane regimen are eligible if the patient is unwilling or the patient's physician deems the patient unsuitable to receive a second regimen.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: 177Lu-PSMA-617
    Patients randomized to receive the investigational product will receive 7.4 GBq (±10%) 177Lu-PSMA-617 intravenously every 6 weeks (±1 week) for a maximum of 6 cycles. After 4 cycles, patients will be assessed for (1) evidence of response, (2) residual disease, and (3) tolerance to 177Lu-PSMA-617. If all 3 assessments are met the patient may receive an additional 2 cycles of 177Lu-PSMA-617.
  • Other: Best supportive/best standard of care
    Best supportive/best standard of care as defined by the local investigator
    Other Name: Comparator
Study Arms  ICMJE
  • Experimental: 177Lu-PSMA-617 plus BS/BSC
    Patients randomized to receive the investigational product will receive 7.4 GBq (±10%) 177Lu-PSMA-617 intravenously every 6 weeks (±1 week) for a maximum of 6 cycles. + Best supportive/best standard of care (BS/BSOC)
    Interventions:
    • Drug: 177Lu-PSMA-617
    • Other: Best supportive/best standard of care
  • BS/BSC alone
    Patients randomized to this arm will receive best supportive/best standard of care (BS/BSOC) as determined by the investigator
    Intervention: Other: Best supportive/best standard of care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 26, 2018)
750
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • To qualify for enrollment, patients must meet the following criteria:

    1. Patients must have the ability to understand and sign an approved ICF.
    2. Patients must have the ability to understand and comply with all protocol requirements.
    3. Patients must be ≥18 years of age.
    4. Patients must have an ECOG performance status of 0 to 2.
    5. Patients must have a life expectancy >6 months.
    6. Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.
    7. Patients must have a positive 68Ga-PSMA-11 PET/CT scan, as determined by the sponsor's central reader.
    8. Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L).
    9. Patients must have received at least one NAAD (such as enzalutamide and/or abiraterone).
    10. Patients must have been previously treated with at least 1, but no more than 2 previous taxane regimens. A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a patient has received only 1 taxane regimen, the patient is eligible if:

      1. The patient is not willing to receive a second taxane regimen, or
      2. The patient's physician deems him unsuitable to receive a second taxane regimen (e.g. frailty assessed by geriatric or health status evaluation or intolerance).
    11. Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria:

      1. Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL.
      2. Soft-tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions.
      3. Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria, Scher et al 2016).
    12. Patients must have≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained ≤28 days prior to beginning study therapy.
    13. Patients must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e. prior chemotherapy, radiation, immunotherapy, etc.).
    14. Patients must have adequate organ function:

      1. Bone marrow reserve:

        • White blood cell (WBC) count ≥2.5 x 109/L (2.5 x 10^9/L is equivalent to 2.5 x 10^3/µL and 2.5 x K/µL and 2.5 x 10^3/cumm and 2500/µL) OR absolute neutrophil count (ANC) ≥1.5 x 10^9/L (1.5 x 10^9/L is equivalent to 1.5 x 10^3/µL and 1.5 x K/µL and 1.5 x 10^3/cumm and 1500/µL)
        • Platelets≥ 100 x 10^9/L (100 x 10^9/L is equivalent to 100 x 10^3/µL and 100 x K/µL and 100 x 10^3/cumm and 100,000/µL)
        • Hemoglobin≥ 9 g/dL (9 g/dL is equivalent to 90 g/L and 5.59 mmol/L)
      2. Hepatic:

        • Total bilirubin ≤1.5 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤ 3 x ULN is permitted
        • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases
      3. Renal:

        • Serum creatinine ≤1.5 x ULN or creatinine clearance ≥50 mL/min
    15. Albumin >3.0 g/dL (3.0 g/dL is equivalent to 30 g/L)
    16. Patients on a stable bisphosphonate or denosumab regimen for ≥30 days prior to randomization are eligible.
    17. HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial.

      For patients who have partners of childbearing potential:

    18. Partner and/or patient must use a method of birth control with adequate barrier protection, deemed acceptable by the principle investigator during the study and for 3 months after last study drug administration.

Exclusion Criteria:

  • Patients who meet any of the following criteria will be excluded from the study:

    1. Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation within 6 months prior to randomization. Previous PSMA-targeted radioligand therapy is not allowed.
    2. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to day of randomization.
    3. Any investigational agents within 28 days prior to day of randomization.
    4. Known hypersensitivity to the components of the study therapy or its analogs.
    5. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
    6. Transfusion within 30 days of randomization.
    7. Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast).
    8. A superscan as seen in the baseline bone scan.
    9. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
    10. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation.
    11. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with adequately treated non-melanoma skin cancer, superficial bladder cancer and patients with prior history of malignancy who have been disease free for more than 3 years are eligible.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Prostate cancer
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Richard Messmann, MD 765-476-1070 rmessmann@endocyte.com
Contact: Wendy Perez 317-608-0590 wperez@endocyte.com
Listed Location Countries  ICMJE Belgium,   Canada,   Denmark,   France,   Netherlands,   Puerto Rico,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03511664
Other Study ID Numbers  ICMJE PSMA-617-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Endocyte
Study Sponsor  ICMJE Endocyte
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Richard Messmann, MD Endocyte
PRS Account Endocyte
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP