Overview
This phase IV studies how to improve the use of Lu 177 vipivotide tetraxetan (177Lu-prostate-specific membrane antigen [PSMA]-617) for treating patients with castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) utilizing a treatment pause after 5 cycles versus standard continuous 6 cycles. Lutetium is a radioligand therapy (RLT). RLT uses a small molecule (in this case 177Lu-PSMA-617) that carries a radioactive component to destroy tumor cells. When lutetium is injected into the body, it attaches to the PSMA receptor found on tumor cells. After lutetium attaches to the PSMA receptor, its radiation component destroys the tumor cell. Giving 177Lu-PSMA-617 for 5 cycles versus 6 cycles may better treat patients with metastatic castrate resistant prostate cancer.
Description
PRIMARY OBJECTIVES:
To determine whether progression-free survival (PFS) is non-inferior among patients randomized to treatment pause versus standard treatment in patients with metastatic castrate resistant prostate cancer (mCRPC) who have minimal residual disease on post-therapy single photon emission computed tomography (SPECT) after 5 cycles of 177Lu-PSMA-617 treatment.
SECONDARY OBJECTIVES:
I. To assess time to subsequent treatment (TTST) in this patient population for each randomized arm.
II. To assess time to progression (TTP) between randomized arms in this patient population for each randomized arm.
III. To assess overall survival (OS) in this patient population for each randomized arm.
IV. To compare toxicities in treatment pause versus standard treatment in this patient population.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive 177Lu-PSMA-617 intravenously (IV) over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-prostate specific membrane antigen-11 (gallium Ga 68-labeled PSMA-11) IV and undergo positron emission tomography (PET)/computed tomography (CT) and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
ARM II: Patients receive 177Lu-PSMA-617 IV over 10-15 minutes on day 1 of each cycle. Cycles repeat every 42 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo clinical observation until documented first progression. Patients may resume treatment with 77Lu-PSMA-617. Patients receive gallium Ga 68-labeled PSMA-11 IV and undergo PET/CT and a bone scan during screening and on the trial. Patients also undergo SPECT/CT and blood sample collection on the trial.
After completion of study treatment, patients who achieved complete response, partial response, or stable disease are followed up at 3 months, then every 3 months for 1 year, and then every 6 months for up to 3 years from time of registration.
Eligibility
Inclusion Criteria:
- REGISTRATION INCLUSION CRITERIA
- Histologically confirmed diagnosis of prostate cancer
- Referred to Mayo Clinic Rochester for therapy with 177Lu PSMA-617
- PSMA positive metastatic castration resistant prostate cancer (68Ga and 18F PSMA PET will be considered equivalent for eligibility) , defined by molecular imaging prostate specific membrane antigen (miPSMA) score >= 2 on Mayo PET report, including interpretation of outside PET
- Prior treatment: Patients must meet FDA label indication, having previously received:
- Androgen receptor pathway inhibition (abiraterone acetate, apalutamide, enzalutamide, darolutamide, or investigational androgen receptor targeted therapy)
- Taxane based chemotherapy (docetaxel and/or cabazitaxel)
- Willingness to provide mandatory blood draws for correlative research. (This
requirement is waived for patients enrolling after receiving cycle 1 of 177Lu PSMA-617, as these patients will not be able to provide a pre-treatment baseline blood sample.)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2. (Make sure to list the possible options 0,1 or 2 and not as a range per Study Build)
- Hemoglobin ≥ 9.0 g/dL (obtained ≤ 30 days prior to registration)
- Absolute neutrophil count (ANC) ≥ 1500/mm^3 (obtained ≤ 30 days prior to registration)
- Platelet count ≥ 100,000/mm^3 (obtained ≤ 30 days prior to registration)
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 30 days prior to registration)
- Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 30 days prior to registration)
- Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained ≤ 30 days prior to registration)
- Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula (obtained ≤ 30 days prior to registration)
- Provide written informed consent
- Ability to complete questionnaire(s) by themselves or with assistance
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- RANDOMIZATION INCLUSION CRITERIA
- Visible lesions on cycle 1 post therapy SPECT, demonstrating that a negative follow up post-therapy scan is attributable to response, rather than sensitivity differences between pre-treatment PET
- Near-complete response on post-therapy SPECT following cycles 2-5 of 177Lu PSMA-617. Near-complete response will be defined as no lesions with SUV max above the mean SUV of a representative 2cm spherical region of interest in the central right hepatic lobe, as determined by a nuclear medicine trained radiologist blind to the locations of previously PSMA avid lesions
- No toxicity that would indicate withholding or reducing dose of the next scheduled cycle of 177Lu PSMA-617 per prescribing information
- Hemoglobin (Hgb) < 10 g/dL
- Platelets < 75,000/mm^3
- Neutrophils < 1500/mm^3
- Glomerular filtration rate (GFR) < 30 mL/min using Cockcroft-Gault formula
- Creatinine > 1.5x baseline patient-specific baseline, defined as average of 2 prior measurements (if available)
- Dry mouth limiting oral intake to purees or soft/moist foods
- Diarrhea, nausea or constipation causing inability to complete instrumental activities of daily living (ADL) or requiring medical intervention to maintain hydration and alimentation
- Fatigue not relived by rest, limiting instrumental ADL
- AST or ALT > 5x upper limit of normal
- Other unacceptable toxicity in the clinical judgement of the investigators
- RE-REGISTRATION INCLUSION CRITERIA (CROSSOVER TO COMPLETION UPON FIRST PROGRESSION OF PATIENTS RANDOMIZED TO TREATMENT PAUSE)
- First progression in patients randomized to pause treatment
- PSMA avid lesions on PSMA PET (miPSMA score ≥ 2 within 30 days of resuming therapy)
Exclusion Criteria:
- REGISTRATION EXCLUSION CRITERIA
- Another active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy
- Receiving any other investigational agent which would be considered as a treatment for the prostate cancer
- Failure to recover from acute, reversible effects of prior therapy regardless of
interval since last treatment
- EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
- Uncontrolled intercurrent non-cardiac illness including, but not limited to:
- Ongoing or active infection
- Psychiatric illness/social situations
- Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
- Any other conditions that would limit compliance with study requirements
- Immunocompromised patients and patients known to be HIV positive and currently
receiving antiretroviral therapy
- NOTE: Patients known to be human immunodeficiency virus (HIV) positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
- Any of the following because this study involves: An investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
- Persons able to father a child who are unwilling to employ adequate contraception
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- History of myocardial infarction ≤6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- RE-REGISTRATION EXCLUSION CRITERIA
- Serious adverse effect