PSMAcTION: A phase II/III, open-label, international, multi-center, randomized study of AAA817 versus standard of care in the treatment of adult participants with PSMA-positive metastatic castration-resistant prostate cancer who progressed on or after [177Lu]Lu-PSMA targeted therapy.
Investigating Treatment Options for a Type of Prostate Cancer with PSMA Protein
Nabil Adra, MD
Primary Investigator
Brief description of study
This is a Phase II/III study. Patient population is adult participants with PSMA-positive mCRPC who had treatments with androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy and progressed on or after [177Lu]Lu-PSMA targeted therapy.
Treatment of interest: the investigational treatment is AAA817 regardless of subsequent anti-neoplastic treatment. The control treatment is investigator's choice of Standard of Care, regardless of subsequent anti-neoplastic treatment.
Detailed description of study
Study CAAA817A12201 consists of 2 parts: a randomized, open-label, international, multicenter, phase II study (Phase II) to collect more information to support the proposed dose of AAA817 and a randomized, open-label, international, multicenter, 2- arm phase III study (Phase III) aimed to evaluate the efficacy and safety of proposed dose of AAA817 vs. investigator's choice of standard of care (SoC) in the treatment of adult participants with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had treatments with ARPI and taxane-based chemotherapy, and progressed on or after [177Lu]Lu-PSMA targeted therapy. The purpose of the phase II part (Phase II) of this study is to collect additional information to support proposed phase III dose of AAA817.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: PSMA-positive metastatic castration-resistant prostate cancer
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Age: 18 years - 100 years
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Gender: Male
Inclusion Criteria: ∙
- adults ≥ 18 years of age.
- ECOG performance status of 0 to 2.
- histopathological and/or cytological confirmation of adenocarcinoma of the prostate.
- PSMA-positive disease as assessed by PSMA PET/CT scan using an approved PSMA imaging agent as protocol instructed,
- castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
- Prior treatments with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy, and progressed on or after [177Lu]Lu-PSMA targeted therapy.
- ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to randomization
- eGFR as requested by the sponsor
Exclusion Criteria:
- Any investigational agents within 28 days prior to the day of randomization.
- Any 225Ac-based investigational compound used prior to the day of randomization.
- Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity.
- Concurrent acute kidney injury (renal failure developed between 48 hours to 7 days) or chronic kidney disease (at least 3 months of ongoing renal injury)
- Baseline xerostomia ≥ Grade 2 by CTCAE v.5
- History of uncontrolled hypertension, myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease
- History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, non-invasive malignant colon polyps that have been removed).
This study investigates the treatment of PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) using an investigational medication called AAA817. The purpose of this study is to compare the effects of AAA817 with the standard of care treatment in adults who have already been treated with certain cancer therapies but have not improved. PSMA is a protein found in prostate cancer cells, and mCRPC is a type of prostate cancer that continues to grow even when the amount of testosterone in the body is reduced to very low levels.
Participants in the study will be randomly assigned to receive either the investigational medication or the standard of care treatment. The study will involve different procedures, including imaging tests like CT, MRI, or bone scans to check for cancer spread. A placebo will not be used in this study, meaning all participants will receive active treatment.
- Who can participate: Adults aged 18 and over with PSMA-positive metastatic castration-resistant prostate cancer may be eligible. Key factors include having been treated with androgen receptor pathway inhibitors and taxane-based chemotherapy, and having progressed on or after [177Lu]Lu-PSMA targeted therapy.
- Study details: Participants will be randomly assigned to receive either the investigational medication AAA817 or the standard of care treatment. This will involve undergoing various imaging tests to monitor the cancer's status.