NCT04876651终止3 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 6
- 主要终点
- Comparison of radiographic progression-free survival (rPFS)
研究概览
简要总结
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).
详细描述
This multinational, multicenter, prospective, randomized, controlled, open label Phase 3 study is designed to investigate and confirm the benefits and risks associated with 177Lu DOTA rosopatamab administered together with SoC, as compared to the best SoC alone, in patients with PSMA-positive, metastatic castration-resistant PC (mCRPC) that has progressed despite prior treatment with a novel androgen axis drug (NAAD).
PSMA positivity will be defined by gallium-68 labeled PSMA-11 (68Ga-PSMA-11) positron emission tomography/computerized tomography (PET/CT) as at least one site of metastatic disease with intensity significantly greater than normal liver (i.e., standardized uptake value [SUV] max at least 1.5 times SUV of normal liver.
Approximately 392 eligible adult male will be part of this study. 387 patients will be randomized to one of two groups in a 2:1 ratio to receive one of the treatments below. 5 participants in New Zealand will be enrolled into a sub-study.
- 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.
In parallel to this, 5 participants in New Zealand site, will be enrolled into a sub-study to investigate the biodistribution, pharmacokinetics and dosimetry of 177Lu-DOTA-TLX591(m17). Participants will receive two doses of 177Lu-DOTA-TLX591(m17), 14 days apart.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Be a male, at least 18 years old, with metastatic adenocarcinoma of the prostate defined by histological / pathological confirmation of PC.
- •Be of ECOG Performance Status 0, 1, or 2 and have an estimated life expectancy of ≥6 months.
- •Have metastatic disease (≥1 metastatic lesions present on baseline CT, MRI, or bone scan imaging).
- •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).
- •In the mCRPC setting, must have received a minimum of 12 weeks of prior therapy with a NAAD, either enzalutamide or abiraterone plus prednisone.
- •Should have received one line of prior taxane therapy or have refused or be ineligible for taxanes
- •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:
- •Rising PSA values done in sequence at least 1 week apart and with a minimal starting value of 2.0 ng/mL.
- •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).
- •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.
- •Must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e., surgery, local radiotherapy, NAAD, chemotherapy, etc.).
- •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.
- •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.
- •Have the capacity to understand the study and be able and willing to comply with all protocol requirements.
- •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.
- •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).
排除标准
- •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.
- •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.
- •Uncontrolled pain.
- •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.
- •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.
- •Have received prior treatment with monoclonal antibody (mAb) J591 or HuJ591 or any other PSMA targeted therapy.
- •Have known allergies, hypersensitivity, or intolerance to the investigational drug or its excipients.
- •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.
- •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.
- •Have received other investigational therapy within 4 weeks of randomization.
- •Have known brain metastases or hepatic metastases.
- •Have a history of seizure and/or stroke within past 6 months.
- •Have clinical or radiologic findings indicative of impending cord compression or experience symptomatic cord compression.
- •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.
- •Have received treatment with any PARP inhibitors (i.e., Olaparib) or with any platinum based anti-neoplastic drugs.
- •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
研究组 & 干预措施
Group A
Experimental
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
干预措施: 177Lu-DOTA-rosopatamb (Other)
Group B
Active Comparator
Participants will receive the Standard of Care
干预措施: Standard of Care (Drug)
Biodistribution and Dosimetry Sub-Study
Experimental
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
干预措施: 177Lu-DOTA-rosopatamb (Other)
结局指标
主要结局
Comparison of radiographic progression-free survival (rPFS)
时间窗: 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).
次要结局
- Overall survival(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Time to a first Symptomatic Skeletal Event (SSE)(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Progression-free survival(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Health-related quality of life by ECOG(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Health-related quality of life by FACT-P(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Health-related quality of life by BPI-SF(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Tumour objective response rate (ORR)(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Adverse events of special interest (AESI)(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Time to radiographic soft tissue progression (TTSTP)(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- To determine whole body biodistribution (BD) of administered activity 177Lu-DOTATLX591(m17)(Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab)
- Health-related quality of life by EQ-5D-5L(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Assessment of changes in prostate specific antigen (PSA)(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Development of anti-drug antibodies (ADA) to 177Lu-DOTA-TLX591(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Neutralizing anti-drug antibodies (NAb) to 177Lu-DOTA-TLX591(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Biochemical response as indicated by PSA levels, lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Titer of anti-drug antibodies (ADA) to 177Lu-DOTA-TLX591(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Duration of positiveness in the development of anti-drug antibodies (ADA) to 177Lu-DOTA-TLX591(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
- Demonstrate comparability of whole body biodistribution dosimetry of the 177Lu-DOTA-TLX591(Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab)
- Demonstrate comparability of organ uptake dosimetry of the 177Lu-DOTA-TLX591(Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab)
- To determine organ radiation dosimetry of tracer levels of administered activity 177Lu-DOTATLX591(m17)(Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab)
- To determine pharmacokinetics (PK) of administered activity 177Lu-DOTATLX591(Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab)
- Demonstrate organ radiation dosimetry comparability of the 177Lu-DOTA-TLX591(Day 1 to day 23 after two administrations of 177Lu-DOTA-rosopatamab)
- Health-related quality of life by EORTC/QQ-C30(Day 1 to 5 years after two administrations of 177Lu-DOTA-rosopatamab)
研究者
研究点 (6)
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