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177Lu-DOTA-rosopatamab With Best Standard of Care (SoC) for the Second Line of Treatment for Metastatic Castrate-resistant Prostate Cancer, Which Expresses PSMA (PROSTACT)

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ClinicalTrials.gov Identifier: NCT04876651
Recruitment Status : Not yet recruiting
First Posted : May 6, 2021
Last Update Posted : October 6, 2021
Sponsor:
Information provided by (Responsible Party):
Telix International Pty Ltd

Brief Summary:
This multinational, multicenter, prospective, randomized, controlled, open label Phase 3 study is designed to investigate and confirm the benefits and risks associated with the PSMA-targeted antibody, 177Lu DOTA rosopatamab administered together with Standard of Care (SoC), as compared to the best SoC alone. The phase 3 will be conducted in patients with metastatic castration-resistant PC (mCRPC) that expresses PSMA and has progressed despite prior treatment with a novel androgen axis drug (NAAD).

Condition or disease Intervention/treatment Phase
Metastatic Prostate Cancer Other: 177Lu-DOTA-rosopatamb Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 387 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Approximately 387 eligible patients will be randomized to one of two groups in a 2:1 ratio to receive one of the following treatments:

  • Group A: Two single intravenous (IV) injections of 76 mCi each (equivalent to a 45 mCi/m2 dose in a standard 1.7m2 individual) of 177Lu-DOTA- rosopatamab, given 14 days apart, plus best SoC
  • Group B: Best SoC.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multinational, Multicenter, Prospective, Randomized, Controlled, Open Label Phase 3 Study With Best Standard of Care With and Without 177Lu-DOTA-rosopatamab for Patients With PSMA Expressing Metastatic Castration-resistant Prostate Cancer Progressing Despite Prior Treatment With a Novel Androgen Axis Drug
Estimated Study Start Date : March 15, 2022
Estimated Primary Completion Date : June 1, 2024
Estimated Study Completion Date : June 1, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Group A
Two single intravenous (IV) injections of 76 mCi each (equivalent to a 45 mCi/m2 dose in a standard 1.7m2 individual) of 177Lu-DOTA- rosopatamab, given 14 days apart, plus best Standard of Care
Other: 177Lu-DOTA-rosopatamb
Two single intravenous (IV) injections of 76 mCi each (equivalent to a 45 mCi/m2 dose in a standard 1.7m2 individual) of 177Lu-DOTA- rosopatamab, given 14 days apart, plus best SoC
Other Name: 177Lu-TLX591

Active Comparator: Group B
Participants will receive the Standard of Care
Other: 177Lu-DOTA-rosopatamb
Two single intravenous (IV) injections of 76 mCi each (equivalent to a 45 mCi/m2 dose in a standard 1.7m2 individual) of 177Lu-DOTA- rosopatamab, given 14 days apart, plus best SoC
Other Name: 177Lu-TLX591




Primary Outcome Measures :
  1. Comparison of radiographic progression-free survival (rPFS) [ Time Frame: Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab ]
    Radiographic progression-free survival (rPFS) defined as the time from randomization to disease progression confirmed by central independent radiology review according to RECIST 1.1 (for soft tissue disease) and/or PCWG3 criteria (for bone disease), or death (whichever occurs first).


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab ]
    Overall survival (OS), determined from randomization, until death from any cause

  2. Tumour objective response rate (ORR) [ Time Frame: Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab ]
    Tumor response in terms of objective response rate (ORR) (malignant soft tissue response and overall radiological response [malignant soft tissue response by RECIST 1.1 and overall radiological response by RECIST 1.1 and PCWG3]).

  3. Time to a first Symptomatic Skeletal Event (SSE) [ Time Frame: Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab ]
    Time to a first SSE, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-vertebral), or occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention

  4. Progression-free survival [ Time Frame: Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab ]
    PFS defined as the time from randomization to disease progression confirmed by radiology, clinical or PSA progression, or death (whichever occurs first).

  5. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab ]
    Assessment of AEs graded by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0, vital signs (systolic and diastolic blood pressures, respiratory rate, pulse rate, and body temperature), ECGs, and evaluation of laboratory parameters (biochemistry, hematology, coagulation, and urinalysis).

  6. Number of participants with Grade 4 hematological abnormalities and bleeding events. [ Time Frame: Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab ]
    Assessment of any Grade 4 hematological abnormalities and bleeding events.

  7. Changes in ECOG Performance scale [ Time Frame: Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab ]
    Quality of Life is to be evaluated using the ECOG Performance Scale, Functional Assessment of Cancer Therapy-Prostate (FACT-P), and Brief Pain Inventory - Short Form (BPI-SF) questionnaires

  8. Assessment of changes in prostate specific antigen (PSA) [ Time Frame: Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab ]
    Percentage change from baseline in PSA level, PSA response, and PSA response duration



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
Criteria

Inclusion Criteria:

  1. Be a male, at least 18 years old, with metastatic adenocarcinoma of the prostate defined by histological / pathological confirmation of PC.
  2. Be of ECOG Performance Status 0, 1, or 2 and have an estimated life expectancy of ≥6 months.
  3. Have metastatic disease (≥1 metastatic lesions present on baseline CT, MRI, or bone scan imaging).
  4. Have castration-resistant PC (defined as disease progressing despite castration by orchiectomy or ongoing use of luteinizing hormone-releasing hormone [LHRH]) and must have a castrate level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L).
  5. In the mCRPC setting, must have received a minimum of 12 weeks of prior therapy with a NAAD, either enzalutamide or abiraterone plus prednisone.
  6. Should have received one line of prior taxane therapy or have refused or be ineligible for taxanes
  7. Have a disease that is progressing at study entry, despite a castrate testosterone level (<50 ng/dL or <1.7 nmol/L), by the demonstration of at least one of the following:

    1. Rising PSA values done in sequence at least 1 week apart and with a minimal starting value of 2.0 ng/mL.
    2. Progressive disease or new lesion(s) in the viscera or lymph nodes as per RECIST1.1 or in bone as per Prostate Cancer Working Group 3 [PCWG3; Scher et al., 2016]). Any ambiguous results are to be confirmed by other imaging modality (e.g., CT or MRI scan).
  8. Have disease that is PSMA positive, as demonstrated by a 68Ga-PSMA11 PET/CT scan and confirmed as eligible by the Sponsor's central reader (patient must have at least one site of metastatic disease with SUVmax ≥1.5 times the SUV of normal liver). If the disease meets the criteria for PSMA positivity, but there is one or more soft tissue lesion of ≥ 2 cm that is not PSMA positive, then the patient is to be excluded on the grounds that there is substantial disease which might not respond to the therapy.
  9. Must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e., surgery, local radiotherapy, NAAD, chemotherapy, etc.).
  10. Can be receiving a bisphosphonate or denosumab regimen provided that the patient has been receiving and tolerating this treatment for ≥30 days prior to randomization.
  11. Have adequate organ function at Screening:

    a. Bone marrow: i. Platelets ≥150×109/L. ii. Absolute neutrophil count >1.5×109/L. iii. Hemoglobin ≥10g/dL (no red blood cell transfusion in the previous 4 weeks).

    b. Liver function: i. Total bilirubin < 1.5×the upper limit of normal (ULN). For patients with known Gilbert's Syndrome <3×ULN is permitted. ii. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <3×ULN OR <5×ULN for patients with liver metastases. c. Renal function: i. Serum/plasma creatinine <1.5×ULN or creatinine clearance ≥50 mL/min determined using the Cockcroft & Gault formula.

  12. Have the capacity to understand the study and be able and willing to comply with all protocol requirements.
  13. Patients must comply with the radiation protection rules (including hospital admissions and isolation) that are used by the treating institution in order to protect their contacts and the general public, especially if a female partner of the patient is or could be pregnant.
  14. Must agree to practice adequate precautions to prevent pregnancy in a partner and to avoid potential problems associated with radiation exposure to the unborn child (Refer to Clinical Trials Facilitation Group, 2020: Recommendations related to contraception and pregnancy testing in clinical trials Version 1.1, CTFG, 2020).

Exclusion Criteria:

  1. Are unable to understand or are unwilling to sign a written informed consent document or to follow investigational procedures in the opinion of the Investigator.
  2. Have PC associated with pathological findings consistent with small cell or any histology other than adenocarcinoma of the prostate. If there are minor elements of neuroendocrine histology, this is acceptable.
  3. Uncontrolled pain.
  4. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, patients with a prior history of malignancy that has been adequately treated and who have been disease-free for more than 3 years are eligible, as are patients with adequately treated non-melanoma skin cancer, and superficial bladder cancer.
  5. Are at increased risk of hemorrhage or bleeding, or with a recent history of a thrombolytic event (e.g., deep vein thrombosis [DVT]/ pulmonary embolism [PE]) and have been administered long-term anti-coagulant or anti-platelet agents.
  6. Have received prior treatment with monoclonal antibody (mAb) J591 or HuJ591 or any other PSMA targeted therapy.
  7. Have known allergies, hypersensitivity, or intolerance to the investigational drug or its excipients.
  8. Have received prior systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy, or biological therapy) and/or radiation therapy within 4 weeks of randomization OR if any significant AEs have not resolved to National Cancer Institute (NCI) AE Criteria ≤2; OR are receiving other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
  9. Have received prior treatment with radioisotopes, including but not limited to: 89Strontium, 153Samarium, 186Rhenium, 188Rhenium, 223Radium, or hemi-body irradiation within 6 months prior to randomization.
  10. Have received other investigational therapy within 4 weeks of randomization.
  11. Have known brain metastases or hepatic metastases.
  12. Have a history of seizure and/or stroke within past 6 months.
  13. Have clinical or radiologic findings indicative of impending cord compression or experience symptomatic cord compression.
  14. Have a serious active or sub-clinical infection or angina pectoris (New York Heart Association [NYHA] Class III or IV), significantly prolonged QT interval or other serious illness(es) involving the cardiac, respiratory, central nervous system, renal, hepatic or hematological organ systems, which might impair the ability to complete this study or could interfere with determination of causality of any adverse effects experienced in this study, or which require treatment that could interact with study treatment, particularly with enzalutamide.
  15. Have received treatment with any PARP inhibitors (i.e., Olaparib) or with any platinum based anti-neoplastic drugs.
  16. Have a known alteration in breast cancer genes (BRCA) BRCA1, BRCA2, or Ataxia Telangiectasia Mutated Gene (ATM) gene and are eligible to receive Olaparib therapy according to their institution's SoC

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): NCT04876651


Contacts
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Contact: Nat Lenzo, MD +61 02 8236 3300 nat.lenzo@genesiscare.com
Contact: Tracey Brown, PhD 0412010104 tracey.brown@telixpharma.com

Locations
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Australia, Western Australia
Diagnostic Nuclear Imaging at Hollywood Private Hospital
Perth, Western Australia, Australia, 6009
Contact: Nat Lenzo, MD    +61 02 8236 3300    nat.lenzo@genesiscare.com   
GenesisCare SJOG Medical Centre, Murdoch WA
Perth, Western Australia, Australia, 6150
Contact: Nat Lenzo, MD    +61 02 8236 3300    nat.lenzo@genesiscare.com   
Sponsors and Collaborators
Telix International Pty Ltd
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Responsible Party: Telix International Pty Ltd
ClinicalTrials.gov Identifier: NCT04876651    
Other Study ID Numbers: 177Lu-TLX591-002
First Posted: May 6, 2021    Key Record Dates
Last Update Posted: October 6, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Telix International Pty Ltd:
prostate cancer
177Lu-DOTA-TLX591
progression free survival
overall survival
safety
gallium-68 labeled PSMA-11 (68Ga-PSMA-11) PET/CT Scan
novel androgen axis drug
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases