Dose Escalation and Efficacy Study of 212Pb-ADVC001 in Patients With Metastatic Castration Resistant Prostate Cancer.
Study Details
Study Description
Brief Summary
This is a first-in-human, dose escalation and efficacy study of [212Pb]Pb-ADVC001 in participants with PSMA-positive metastatic Castration Resistant Prostate Cancer (mCRPC) who have not had prior exposure to [177Lu]Lu-PSMA based radioligand therapies.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
This is a single arm, non-randomized, toxicity and dose finding study. The trial will include a maximum of 18 patients with confirmed mCRPC and no prior history of radioligand therapy.
The study is based on a 3 + 3 design with 4 cohorts of patients receiving escalating doses 60, 90, 120 and 150MBq of [212Pb]Pb-ADVC001. Each patient in each cohort will be given the same dose and a maximum of 4 cycles of therapy administered at 6 weekly intervals.
The decision to recruit the next cohort of patients and escalate the dose will be made after reviewing all safety data from the previous cohort acquired over 6 weeks after the first cycle of therapy. In this manner, recruitment of the next cohort can occur before all treatment cycles have been administered to the previous cohort.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: [212Pb]Pb-ADVC001 There is only a single treatment arm. Participants with metastatic Castration Resistant Prostate Cancer that have received prior Androgen Receptor Pathway Inhibitors (e.g., Abiraterone, Enzalutamide) and chemotherapy (or can have declined chemotherapy), who have not been previously treated with [177Lu]Lu-PSMA radioligand therapy. Four cohorts will receive escalating doses of 60 MBq, 90 MBq, 120MBq and 150MBq of [212Pb]Pb-ADVC001. Participants will receive a dose via intravenous injection every 6 weeks (+/- 2 weeks) for no more than 4 cycles. |
Drug: [212Pb]Pb-ADVC001
[212Pb]Pb-ADVC001 administered intravenously under the dose escalation schedule
Other Names:
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Outcome Measures
Primary Outcome Measures
- Recommended Phase 2 Dose (RP2D) for [212Pb]Pb-ADVC001. [6 weeks after the first cycle of therapy (each cycle is 42 days) for each dose escalation cohort through to competition of enrolment, an average of 52 weeks to determine RP2D]
The RP2D is defined as the dose level that is well tolerated in patients. This will be equal or less than the Maximum Tolerated Dose (MTD). In the case where an MTD is not identified, even at the highest dose level tested, the RP2D may be determined based on data indicating adequate tolerability and therapeutic effectiveness.
Secondary Outcome Measures
- Determine tumour response based on contrast CT imaging and [68Ga]Ga-PSMA-11 PET/CT imaging. [Patients are administered a maximum of 4 cycles of therapy, 6 weeks apart. Images will be acquired at baseline and 6 weeks after the 2nd and 4th cycle of therapy. Each cycle is 42 days. This equates to a period of 52 weeks to measure tumour response.]
Tumour response for contrast CT will be monitored using RECIST 1.1 assessment criteria. [68Ga]Ga-PSMA-11 PET images will be evaluated using the consensus statement on PSMA PET/CT response assessment criteria.
- Determine change in PSA levels as a measure of treatment response. [Patients are administered a maximum of 4 cycles of therapy 6 weeks apart. PSA levels will be assessed at baseline and every 6 weeks and at 3 months after the last cycle of therapy. Each cycle is 42 days. This equates to a total period of 52 weeks.]
Tumour response will be measured by a decline in PSA level compared to baseline levels.
- To determine clearance and cumulative blood activity of 212Pb after the first cycle of therapy. [Blood draws for measuring 212Pb activity will occur at 10 minutes, 1 and 4 hours and 1 hour prior to release of the patient from hospital only after the 1st cycle of therapy (cycle is 42 days). The maximum time frame for these measures will be 24 hours.]
212Pb activity in blood will be measured using a bench top gamma counter.
- To determine clearance and cumulative activity of 212Pb in urine after the first cycle of therapy. [212Pb activity in urine will be measured at 1 and 4 hours and 1 hour prior to release of the patient from hospital only after the 1st cycle of therapy (each cycle is 42 days). The maximum time frame for these measures will be 24 hours.]
212Pb activity in urine will be measured using a bench top gamma counter.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male and 18 years of age or older at the time of signing the consent form with metastatic adenocarcinoma of the prostate, defined by documented histopathology of prostate adenocarcinoma or metastatic disease typical of prostate cancer (i.e., Involving bone and /or lymph nodes)
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Patients with castration-resistant prostate cancer that have progressed on androgen receptor therapy and exposure to a taxane-based chemotherapy at any time in the course of their disease, unless considered contraindicated by a medical oncologist or patient declines treatment
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Progressive disease with rising PSA level, defined by PCWG3 criteria (sequence of two rising values above a baseline at a minimum of 1-week intervals), and PSA > 20 ng/mL Significant PSMA avidity on [68Ga]Ga-PSMA PET/CT, defined as a minimum uptake of SUVmax of 20 at a site of disease, and SUVmax > 10 at sites of measurable disease ≥10 mm (unless subject to factors explaining a lower uptake, e.g., respiratory motion, reconstruction artefact) ECOG Performance status 0 to 2
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Adequate renal, bone and liver function (Absolute neutrophil count: ≥2 x 109/L , Hemoglobin: ≥90 g/L, Platelet count: >150,000 x 109/L, Serum creatinine: <1.5 x upper limit of normal (ULN) i.e ≤ 125 umol/L or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault formula, Serum total bilirubin: <1.5 x ULN (unless the patient has Gilbert's syndrome in which case direct bilirubin must be normal), Serum AST and ALT: <1.5 x ULN in the absence of liver metastases; <3 x ULN if due to liver metastases (in both circumstances bilirubin must meet entry criteria)
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Estimated life expectancy >12 weeks
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Willing and able to comply with all study requirements, including the timing and nature of all required assessments (i.e., blood testing and scanning.)
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Have provided written Informed Consent for participation in this trial and can commence study treatment within 14 days after the completion of screening
Exclusion Criteria:
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Prostate cancer with known significant sarcomatoid or spindle cell or neuroendocrine small cell components
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Site(s) of disease that are FDG positive with minimal PSMA expression defined as FDG intensity > 68Ga-PSMA activity or 68Ga-PSMA SUVmax < 10
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Sjogren's syndrome
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ECOG status >2
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Prior treatment with [177Lu]Lu- or [225Ac]Ac-PSMA based radioligand therapy
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Complete or partial obstruction of outflow of a kidney
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Contraindications to the use of corticosteroid treatment
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Active malignancy other than prostate cancer (excluding non-melanomatous skin cancers)
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Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
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Serious psychological, familial, sociological, or geographical condition that might hamper compliance with the study protocol and follow-up schedule
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Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception
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Severe claustrophobia that may impact the participants ability to comply with all aspects of the imaging protocol
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Royal Brisbane & Women's Hospital | Brisbane | Queensland | Australia | 4029 |
Sponsors and Collaborators
- AdvanCell Isotopes Pty Limited
Investigators
- Principal Investigator: David Wyld, Royal Brisbane & Women's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TheraPb-ADVC001