Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer
Purpose
The primary objective of this study was to compare the two alternate primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) in patients with progressive prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA-617 in addition to best supportive/best standard of care (BSC/BSoC) versus patients treated with best supportive/best standard of care alone.
Condition
- Prostate Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Patients must have the ability to understand and sign an approved informed consent form (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 Eastern Cooperative Oncology Group (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 be 68Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan positive, and eligible as determined by the sponsor's central reader. 8. Patients must have a castrate level of serum/plasma 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: a. The patient's physician deems him unsuitable to receive a second taxane regimen (e.g. frailty assessed by geriatric or health status evaluation, intolerance, etc.). 11. Patients must have progressive mCRPC. Documented progressive mCRPC will be based on at least 1 of the following criteria: 1. Serum/plasma 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: a. Bone marrow reserve: - White blood cell (WBC) count >= 2.5 x 10^9/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) b. 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 c. Renal: - Serum/plasma 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) [Inclusion #16 has been removed] 17. HIV-infected patients who are healthy and have a low risk of AIDS-related outcomes are included in this trial. 18. For patients who have partners of childbearing potential: 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 6 months after last study drug administration. 19. The best standard of care/ best supportive care options planned for this patient: 1. Are allowed by the protocol 2. Have been agreed to by the treating investigator and patient 3. Allow for the management of the patient without 177Lu-PSMA-617
Exclusion Criteria
- Previous treatment with any of the following within 6 months of randomization: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. 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 for the sole purpose of making a subject eligible for study inclusion. 7. Patients with a history of Central Nervous System (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, known 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. 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, superficial bladder cancer.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- The study population included 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 containing regimens. Patients treated with only 1 prior taxane regimen were eligible if the patient was unwilling or the patient's physician deemed the patient unsuitable to receive a second regimen.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 177Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC) |
Patients randomized to receive the investigational product received 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) might be used |
|
|
Other Best supportive/best standard of care (BS/BSOC) alone |
Patients randomized to this arm received best supportive/best standard of care (BS/BSOC) as determined by the investigator |
|
More Details
- Status
- Completed
- Sponsor
- Endocyte
Study Contact
Detailed Description
The study for each participant consisted of a Screening period, a Treatment period and a Follow-up period. Screening and randomization: During the screening period of up to 28 days before starting randomized treatment, each participant was assessed for PSMA positivity by gallium (68Ga) gozetotide imaging PET/scan per the pre-defined read rules, by the Sponsor's central reader. Only patients with PSMA-positive metastatic PC and meeting all other inclusion/exclusion criteria were randomized in a 2:1 ratio to receive either 177Lu-PSMA-617 plus BSC/BSoC or BSC/BSoC only. Randomized patients were stratified on the following factors: LDH level (=< or > 260 UI/L), presence of liver metastases (Yes or No), eastern cooperative oncology group (ECOG) score (0-1 or 2) and inclusion of NAAD in the BSC/BSoC (at time of randomization (Yes or No)). Protocol- specified BSC/BSoC for each patient was initiated by the investigating physician prior to patient randomization and maintained throughout the study. On-study changes to BSC/BSoC were allowed and at the discretion of the investigating physician. Randomized treatment: "Randomized treatment" in this study referred to 177Lu-PSMA- 617+BSC/BSoC (investigational arm) and BSC/BSoC only (control arm). Patients randomized to the investigational arm began 177Lu-PSMA-617 administration within 28 days after randomization (C1D1). These patients received 7.4 gigabecquerel (GBq) (+/- 10%) 177Lu-PSMA-617 once every 6 weeks (+/- 1 week) for a maximum of 6 cycles while receiving BSC/BSoC. After Cycle 4 treatment and prior to Cycle 5 treatment, the investigator assessed the following criteria to determine whether: - The patient showed evidence of response (i.e., radiological, PSA, clinical benefit). - The patient had signs of residual disease on CT with contrast/MRI or bone scan. - The patient had shown good tolerance to the 177Lu-PSMA-617 treatment. If the patient met all the criteria above and agreed to continue with additional treatment of 177Lu-PSMA-617, the Investigator could administer 2 additional cycles. A maximum of 6 cycles of 177Lu-PSMA-617 as allowed. If the patient did not meet any of the criteria or did not agree to additional 177Lu-PSMA-617 treatment, then no additional doses of 177Lu-PSMA- 617 were administered after Cycle 4. After the last cycle of 177Lu-PSMA- 617, patients continued to be treated with BSC/BSoC as long as the investigator felt they were clinically benefiting (regardless of radiographic progressive disease based on Investigator's assessment per PCWG3 criteria) or until they required a treatment regimen not allowed on this study. For both treatment arms, the cycle duration for Cycle 1-6 was 6 weeks and for Cycle 7 and beyond, was 12 weeks. From Cycle 7 onwards, all patients from both treatment arms only received BSC/BSoC. End of treatment: The EOT visit was scheduled approximately 30 days after the last dose of 177Lu-PSMA-617 or the date of the BSC/BSoC EOT decision (whichever occurred later), but before the initiation of subsequent anti-cancer treatment, outside of what was allowed on study. Long-term follow-up: Patients who consented to be followed for long-term status updates, entered the long-term follow-up period after the EOT visit. The long-term follow-up included the collection of radiographic images (if a patient discontinued for reasons other than radiographic progression), OS, information about new treatments along with the patient's response to these treatments, AE assessment, and results of hematology and chemistry testing. During the follow-up, patients are contacted every 3 months (+/-1 month) via phone, email, or letter until the end of long-term the follow-up period (24 months after the first patient enters long-term follow-up) or until 508 deaths had occurred.