A Phase 2 Study of Biomarker-Modulated PSMA Theranostics
Overview
- Phase
- Phase 2
- Intervention
- Biospecimen Collection
- Conditions
- Not specified
- Sponsor
- University of Washington
- Enrollment
- 51
- Locations
- 3
- Primary Endpoint
- Prostate-specific antigen (PSA) progression-free survival (PFS)
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
This phase II trial tests how well 177Lu-PSMA-617 works in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that remains despite treatment (resistant). Lutetium Lu 177 (177Lu), the radioactive (tracer) component being delivered by prostate-specific membrane antigen (PSMA)-617, has physical properties that make it ideal radionuclide (imaging tests that uses a small dose tracer) for treatment of metastatic castrate-resistant prostate cancer (mCRPC). 177Lu-PSMA-617 works by binding to prostate cancer cells and inducing damage to deoxyribonucleic acid (DNA) inside prostate cancer cells. Giving 177Lu-PSMA-617 may improve treatment outcomes for patients with mCRPC.
Detailed Description
OUTLINE: Patients receive 177Lu-PSMA-617 intravenously (IV) over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA positron emission tomography/computed tomography (PET/CT) during screening and single photon emission computed tomography (SPECT)/CT on study. Patients also undergo CT or magnetic resonance imaging (MRI), bone scan, as well as blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have the ability to understand and sign an approved informed consent.
- •Patients must have the ability to understand and comply with all protocol requirements.
- •Patients must be ≥ 18 years of age.
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Patients must have a life expectancy \> 6 months.
- •Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.
- •Patients must have a positive 68Ga-PSMA PET/CT scan with no PSMA negative lesion, as determined by the Nuclear Medicine site investigator. The presence of PSMA-positive lesions was defined as 68Ga-PSMA-11 uptake greater than that of liver parenchyma in one or more metastatic lesions of any size in any organ system. PSMA negative disease defined as lymph nodes of 2.5 cm or visceral lesions or soft tissue component of a lytic bone lesion of 1.0 cm or larger with uptake less than that of liver parenchyma.
- •Patients must have whole body tumor SUVmean of \< 10 on 68Ga-PSMA PET/CT scan, as determined by the Nuclear Medicine site investigator. 68GaPSMA PET/CT will be analyzed using a semi-quantitative approach with MIM software (MIM Software Inc.). The workflow identified whole-body regions of interest (ROIs) with an maximum standardized uptake value (SUVmax) greater than 3 and a lesion size of at least 0.5 mm. The reviewer then manually removes any instances of physiological activity or uptake that are not related to the disease. The method of whole-body quantification will automatically calculate the whole body SUVmean.
- •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) at the most recent evaluation before enrollment.
- •Patients must have received at least one androgen receptor pathway inhibitor (ARPI) (such as enzalutamide and/or abiraterone).
Exclusion Criteria
- •Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation within 6 months prior to treatment day
- •Previous PSMA-targeted radioligand therapy is not allowed.
- •Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\]) within 30 days prior to treatment day
- •Concurrent bone strengthening agents such as bisphosphonates (such as zolendronic acid) and RANKL inhibitors (such as denosumab) are allowed.
- •Any investigational agents within 30 days prior to treatment day
- •Known hypersensitivity to the components of the study therapy or its analogs.
- •Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.
- •Transfusion within 30 days of treatment day
- •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.
- •Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
Arms & Interventions
Treatment (177Lu-PSMA-617)
Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.
Intervention: Biospecimen Collection
Treatment (177Lu-PSMA-617)
Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.
Intervention: Bone Scan
Treatment (177Lu-PSMA-617)
Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.
Intervention: Computed Tomography
Treatment (177Lu-PSMA-617)
Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.
Intervention: Lutetium Lu 177 Vipivotide Tetraxetan
Treatment (177Lu-PSMA-617)
Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.
Intervention: Magnetic Resonance Imaging
Treatment (177Lu-PSMA-617)
Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.
Intervention: PSMA PET-CT Scan
Treatment (177Lu-PSMA-617)
Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.
Intervention: Questionnaire Administration
Treatment (177Lu-PSMA-617)
Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.
Intervention: Single Photon Emission Computed Tomography
Outcomes
Primary Outcomes
Prostate-specific antigen (PSA) progression-free survival (PFS)
Time Frame: From enrollment to PSA progression or death from any cause, assessed up to 2 years
PSA progression is defined as a rise in PSA at \> 12 weeks by more than 25% and more than 2ng/mL above the nadir (lowest PSA point). Time-to-event endpoints will be analyzed graphically and numerically using the Kaplan-Meier method and summarized in terms of median or 1-year survival point estimates with corresponding 95% confidence intervals.
Secondary Outcomes
- Incidence of adverse events (AEs)(Up to 30 days post-treatment)
- PSA50 response(Up to 30 days post-treatment)
- Radiographic progression-free survival(From enrollment to radiographic disease progression or death from any cause, assessed up to 2 years)
- Overall response rate (ORR)(Up to 2 years)
- Duration of response (DOR)(Up to 2 years)
- Progression-free survival (PFS)(From enrolment to first evidence of radiographic or clinical progression, or PSA PFS, assessed up to 2 years)
- Overall survival(From enrollment to death from any cause, assessed up to 2 years)
- Pain score(Up to 30 days post-treatment)
- Health-related quality of life: Eastern Cooperative Oncology Group (ECOG) Performance Status scale(Up to 30 days post-treatment)
- Health-related quality of life (HRQoL): Functional Assessment of Cancer Therapy Prostate (FACT-P)(Up to 30 days post-treatment)
- Time to pain progression(From enrollment to pain progression, assessed up to 30 days post-treatment)