Study Description
This is a Phase 1, open-label, international, dose escalation study to evaluate the
safety of [225Ac]Ac-PSMA-617 (225Ac-PSMA-617) in men with PSMA-positive prostate cancer
who have and have not had prior exposure to [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) or
[177Lu]Lu-PSMA I&T (177Lu-PSMA I&T). The study schedule for each patient consists of a screening phase, a treatment phase,
safety and long-term follow up phase, for an overall individual duration of approximately
32 months.
A minimum of 3 patients will be treated in each patient group at each dose level and
evaluated for the occurrence of dose-limiting toxicity (DLT) during the first 6 weeks of
treatment before consideration will be given to enrolling patients into the next dose
level. Dose modifications for toxicity are allowed beyond the first 6 weeks of therapy
and defined per protocol.
No more than 6 cycles of 225Ac-PSMA-617 will be administered. Patients may receive less
than 6 cycles if they have disease progression, intolerable toxicity, started other
anticancer therapy, or have withdrawn from treatment per subject or physician decision.
Subjects may also receive supportive care therapy, as determined by the investigative
physician, however, subjects cannot receive concurrent investigational agents, cytotoxic
chemotherapy, biological agents, targeted therapy, immunotherapy, other systemic
radioisotopes, and hemi-body radiotherapy or novel androgen axis drugs [ARPIs] until
completion of treatment with 225Ac-PSMA-617.
Interventions
225^Ac-PSMA-617
68^Ga-PSMA-11
Eligibility Criteria
Inclusion Criteria:
- Patients must have the ability to understand and sign an approved ICF.
- Patients must have the ability to understand and comply with all protocol
requirements.
- Patients must be >=18 years of age.
- Patients must have an ECOG performance status of 0 to 2.
- Patients must have had histological, pathological, and/or cytological confirmation
of prostate cancer.
- Patients must have a positive 68Ga-PSMA-11 PET/CT scan performed within 28 days of
study entry as described in Imaging Manual).
- Patients must have recovered or stabilized to =< Grade 2 or baseline from all
clinically significant toxicities related to prior prostate cancer therapy.
- Determination of disease progression on treatment prior to enrollment. Progressive
disease for study entry is defined as any one or more of the following:
1. PSA progression: minimum of two rising PSA values from a baseline measurement
with an interval of >= 1 week between each measurement. 2.0 ng/mL is the
minimal starting value if PSA rise is only indication of progression.
2. Soft tissue or visceral disease progression as per RECIST 1.1 criteria:
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. Bone progression: >= 2 new lesions on bone scan.
- Patients must have adequate organ function (bone morrow reserve, hepatic function
and renal function).
- Known HIV-positive patients who are healthy and have a low risk of AIDS-related
outcomes are eligible. HIV testing is required.
- For patients who have partners of childbearing potential, 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.
- Group A Subjects: Patients must have prior orchiectomy and/or ongoing
androgen-deprivation therapy, a castrate level of serum testosterone (< 50 ng/dL or
< 1.7 nmol/L) and must have received prior cytotoxic chemotherapy and a novel
androgen axis drug (e.g., abiraterone or enzalutamide). Patients must also be naïve
to prior 177Lu-PSMA radioligand therapy (177Lu-PSMA-617 or 177Lu-PSMA I&T)
- Group B Subjects (South-Africa only): Patients must have ongoing androgen
deprivation therapy (ADT) and either prior orchiectomy or be medically castrate
using LHRH agonists/antagonists in order to achieve adequate suppression of serum
testosterone (< 50 ng/dL) but must not have received prior cytotoxic chemotherapy or
novel androgen axis drugs (e.g., abiraterone or enzalutamide). These patients are
naïve to 177Lu-PSMA radioligand therapy (177Lu-PSMA-617 or 177Lu-PSMA I&T).
- Group C Subjects: Patients must have ongoing androgen deprivation therapy (ADT) and
either prior orchiectomy or be medically castrate using LHRH agonists/antagonists in
order to achieve adequate suppression of serum testosterone (< 50 ng/dL). Patients
must have been treated with prior 177Lu-PSMA radioligand therapy (177Lu-PSMA-617 or
177Lu-PSMA I&T) for at least one cycle administered greater than 6 weeks from study
enrollment, and been evaluated for biochemical and radiological response to therapy.
Prior exposure to ARPI and/or chemotherapy is not required.
Exclusion Criteria:
- Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188,
Radium-223 or hemi-body irradiation.
- Any investigational agents within 28 days of study enrollment.
- Known hypersensitivity to the components of the study therapy or its analogues.
- Other concurrent cytotoxic chemotherapy, targeted therapy, biologic agents,
immunotherapy, radioligand therapy, or investigational therapy.
- Transfusion for the sole purpose of eligibility into the study.
- Patients with a history of 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.
- Concurrent serious (as determined by the Principal Investigator) medical conditions,
including, but not limited to, uncontrolled infection, active hepatitis B or C, or
other significant co-morbid conditions that in the opinion of the investigator would
impair study participation or cooperation.
- Diagnosed with other malignancies that are expected to alter life expectancy or may
interfere with disease assessment. Patients with a prior history of malignancy who
have been disease free for more than 3 years are eligible.
- Participants with an active documented COVID-19 infection (any grade of disease
severity) at the time of informed consent may be included only when completely
recovered (in accordance with local guidance).
Study Location
St. Vincent's Hospital Research Office-Translational Research Center
Recruiting
Darlinghurst,Australia
Steve Biko Hospital-Department of Nuclear Medicine
Recruiting
Pretoria,South Africa
Worldwide Contacts
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