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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04597411




Registration number
NCT04597411
Ethics application status
Date submitted
29/09/2020
Date registered
22/10/2020

Titles & IDs
Public title
Study of 225Ac-PSMA-617 in Men With PSMA-positive Prostate Cancer
Scientific title
AcTION: A Phase I Study of [225Ac]Ac-PSMA-617 in Men With PSMA-positive Prostate Cancer With or Without Prior [177Lu]Lu-PSMA-617 Radioligand Therapy
Secondary ID [1] 0 0
CAAA817A12101
Secondary ID [2] 0 0
PSMA-617-100
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms, Castration-Resistant 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - 225^Ac-PSMA-617
Treatment: Other - 68^Ga-PSMA-11

Experimental: Group A (mCRPC who have received prior ARPI and chemotherapy, but are PSMA RLT naïve) - Men that have received prior cytotoxic chemotherapy and ARPI (e.g., abiraterone or enzalutamide), who HAVE NOT been previously treated with 177Lu-PSMA-617 radioligand therapy or 177Lu-PSMA I\&T will receive a dose of 225\^Ac-PSMA-617 via intravenous injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles.

Experimental: Group B (mCRPC who have not had prior ARPI or chemotherapy, and are PSMA RLT naïve) - Men previously treated with luteinizing hormone-releasing hormone (LHRH) agonists or orchiectomy and primary anti-androgen therapy that have not received prior cytotoxic chemotherapy or novel androgen axis drugs (e.g., abiraterone or enzalutamide) will receive a dose of 225Ac-PSMA-617 via intravenous injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles.

Experimental: Group C (mCRPC who have received prior PSMA RLT) - Men with progressive metastatic castration resistant prostate cancer (mCRPC) who HAVE been previously treated with 177Lu-PSMA-617 radioligand therapy or 177Lu-PSMA I\&T will receive a dose of 225Ac-PSMA-617 via intravenous injection every 8 weeks (+/- 1 week) for a maximum of 6 cycles. Prior chemotherapy and/or novel androgen axis drugs not required.


Treatment: Other: 225^Ac-PSMA-617
administered intravenously under the dose escalation schedule

Treatment: Other: 68^Ga-PSMA-11
administered intravenously at a dose of 111 - 185 MBq (3 - 5 mCi)
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase 2 Dose (RP2D)
Timepoint [1] 0 0
6 weeks post Cycle 1 Day 1 (C1D1) of each dosing cohort through enrollment completion, an average of 1.5 years to determine RP2D
Secondary outcome [1] 0 0
Percentage of Participants with treatment emergent adverse events
Timepoint [1] 0 0
Day 1/Infusion Day up to 60 days post infusion
Secondary outcome [2] 0 0
Overall Response Rate (ORR)
Timepoint [2] 0 0
Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years
Secondary outcome [4] 0 0
Disease Control Rate (DCR)
Timepoint [4] 0 0
Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years
Secondary outcome [5] 0 0
Progression Free Survival (PFS)
Timepoint [5] 0 0
Every 8 weeks after first dose of 225Ac-PSMA-617 for the first 24 weeks, then every 12 weeks through the end of treatment visit, on average 2.5 years
Secondary outcome [6] 0 0
Percentage of Participants with Biochemical Response as measured by Prostate Specific Antigen (PSA)
Timepoint [6] 0 0
Baseline, Days 1, 15, 29 and 43 of each Cycle (1 cycle = 8 weeks +/- 1 week), End of Treatment and every 3 months during the 12-month follow-up period
Secondary outcome [7] 0 0
Notable Changes in Alkaline phosphatase (ALP) levels
Timepoint [7] 0 0
Baseline, Cycle 1 and Cycle 2 (Weekly), Cycle 3 to Cycle 6 (Bi-weekly) (1 cycle = 8 weeks +/- 1 week)
Secondary outcome [8] 0 0
Notable Changes in Lactate dehydrogenase (LDH) levels
Timepoint [8] 0 0
Baseline, Cycle 1 and Cycle 2 (Weekly), Cycle 3 to Cycle 6 (Bi-weekly) (1 cycle = 8 weeks +/- 1 week)
Secondary outcome [9] 0 0
Change from Baseline in European Quality of Life (EuroQol) - 5 Domain 5 Level scale (EQ-5D-5L)
Timepoint [9] 0 0
Baseline, Day 1 of each Cycle (1 cycle = 8 weeks +/- week), End of Treatment, on average 2.5 years
Secondary outcome [10] 0 0
Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
Timepoint [10] 0 0
Baseline, Day 1 of each Cycle (1 cycle = 8 weeks +/- week), End of Treatment, on average 2.5 years
Secondary outcome [11] 0 0
Change from Baseline in Brief Pain Inventory - Short Form (BPI-SF) Questionnaire: Pain Severity Score
Timepoint [11] 0 0
Baseline, Day 1 of each Cycle (1 cycle = 8 weeks +/- week), End of Treatment, on average 2.5 years
Secondary outcome [12] 0 0
Change from Baseline in Brief Pain Inventory - Short Form (BPI-SF) Questionnaire: Pain Interference Score
Timepoint [12] 0 0
Baseline, Day 1 of each Cycle (1 cycle = 8 weeks +/- week), End of Treatment, on average 2.5 years
Secondary outcome [13] 0 0
Change from Baseline in Xerostomia-Related Quality of Life Scale (XeQOLS)
Timepoint [13] 0 0
Baseline, Day 1 of each Cycle (1 cycle = 8 weeks +/- 1 week), End of Treatment and every 3 months during the 12-month follow-up period

Eligibility
Key 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. If a patient also has soft tissue or visceral disease, it must be PSMA-positive on 68Ga-PSMA-11 PET/CT scan.
* Patients may not participate in the study if their baseline scan shows PSMA-negative disease (defined as disease that expresses PSMA at a level equal to or less than liver by visual assessment) in any of the following regions:

A) One or more PSMA negative lymph nodes >2.5 cm on short axis B) Bone metastasis with PSMA-negative soft tissues component > 1 cm in short axis

* Note that PSMA-negative osseous metastases without a soft tissue component >1 cm does not exclude the subject C) PSMA-negative solid organ metastases (i.e. lung, liver, adrenal glands, etc) that are PSMA-negative and = 1cm in short axis
* 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 principal 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2027
Actual
Sample size
Target
99
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St. Vincent's Hospital Research Office-Translational Research Center - Darlinghurst
Recruitment postcode(s) [1] 0 0
- Darlinghurst
Recruitment outside Australia
Country [1] 0 0
South Africa
State/province [1] 0 0
Pretoria

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Endocyte
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04597411