Understanding the role of TLX591 in patients with metastatic Prostate cancer who failed 2 cycles of Lutetium PSMA therapy
A pilot, feasibility study of 177Lu-DOTA-Rosopatamab (TLX591) therapy in castrate resistant prostate adenocarcinoma patients showing progression on radioligand therapy using PSMA small molecule ligands
Mercy Radiology
10 participants
Mar 6, 2023
Interventional
Conditions
Summary
Therapy for castrate resistant prostate cancer (CRPC) is now increasingly performed in clinical practice with radioligands targeting prostate specific membrane antigen (PSMA), commonly [177Lu]-PSMA I&T or [177Lu]-PSMA-61. Trials show rates of response of up to 80%, but failed therapy in 20 to 30% in terms of overall survival and delayed imaging based progression. Given the current use of PSMA radioligand therapy late in the course of CRPC, patients who fail conventional small molecule therapy have few, or no options for further treatment. TLX591 is a new radioligand targeting PSMA overexpression in prostate adenocarcinoma, currently in evaluation. As TLX591 is an antibody to PSMA, with a different mechanism of binding and internalisation at the cellular level relative to small molecule therapies, we propose it may elicit a therapeutic response in patients who are progressing on small molecule radioligand therapy.
Eligibility
Inclusion Criteria21
- To qualify for enrolment, patients must meet the following criteria:
- Ability to understand and sign an approved Informed Consent Form (ICF).
- Ability to understand and comply with all protocol requirements.
- Males at least 18 years of age and older.
- ECOG performance status of 0 to 2.
- Life expectancy greater than 6 months.
- Patients must have histological, pathological, and/or cytological confirmation of prostate cancer.
- Have metastatic disease (at least 1 metastatic lesion present at baseline CT, MRI, or bone scan imaging).
- Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy.
- Patients must have progressive Metastatic Castrate Resistant Prostate Cancer (mCRPC). Documented progressive mCRPC will be based on:
- a. serum PSA progression defined as 2 consecutive increases in PSA from baseline of more than 25%, following a minimum of 2 cycles of radioligand therapy using PSMA small molecule ligands
- b. appearance of two or more new lesions and/or increase of uptake or tumour PET volume greater than 30%
- Have disease that is PSMA positive, as demonstrated by a 68Ga-PSMA PET/CT scan and without significant discordance at 18FDG PET/CT.
- Must have recovered to at least Grade 2 from all clinically significant toxicities related to prior therapies (i.e., surgery, local radiotherapy, neoadjuvant androgen deprivation (NAAD), chemotherapy, etc.).
- Can be receiving a bisphosphonate or denosumab regimen provided that the patient has been receiving and tolerating this treatment for at least 30 days prior to randomization.
- Have adequate organ function at Screening, including bone marrow, liver and renal function.
- a. Bone marrow: i. Platelets at least 150×109/L. ii. Absolute neutrophil count greater than 1.5×109/L. iii. Haemoglobin at least 10g/dL (no red blood cell transfusion in the previous 4 weeks).
- b. Renal function: i. Serum/plasma creatinine less than 1.5×ULN or creatinine clearance equal to 50 mL/min determined using the Cockcroft & Gault formula.
- c. Liver function: i. Total bilirubin less than 1.5×the upper limit of normal (ULN). For patients with known Gilbert's Syndrome less than 3×ULN is permitted. ii. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 3×ULN OR less than 5×ULN for patients with liver metastases.
- Patients must comply with the radiation protection rules (including hospital admissions and isolation) that are used by the treating institution in order to protect their contacts and the general public, especially if a female partner of the patient is or could be pregnant.
- Must agree to practice adequate precautions to prevent pregnancy in a partner and to avoid potential problems associated with radiation exposure to the unborn child (Refer to Clinical Trials Facilitation Group, 2020: Recommendations related to contraception and pregnancy testing in clinical trials Version 1.1, CTFG, 2020).
Exclusion Criteria11
- Are unable to understand or are unwilling to sign a written informed consent document or to follow investigational procedures in the opinion of the Investigator.
- Uncontrolled pain.
- Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, patients with a prior history of malignancy that has been adequately treated and who have been disease-free for more than 3 years are eligible, as are patients with adequately treated non-melanoma skin cancer, and superficial bladder cancer.
- Are at increased risk of hemorrhage or bleeding, or with a recent history of a thrombotic event (e.g., deep vein thrombosis [DVT]/ pulmonary embolism [PE]) and have been administered long-term anti-coagulant or anti-platelet agents.
- Have known allergies, hypersensitivity, or intolerance to the investigational drug or its excipients.
- Have commenced any new systemic anti-cancer therapy since commencement of Lu-177-PSMA I&T therapy and recruitment or have any significant AE form previous therapy which have not resolved to National Cancer Institute (NCI) AE Criteria 2.
- Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
- Have received other investigational therapy within 4 weeks of treatment.
- Previous Samarium, Strontium or Radium therapy.
- Have a serious active or sub-clinical infection or heart failure (New York Heart Association [NYHA] Class III or IV), or other serious illness(es) involving the cardiac, respiratory, central nervous system, renal, hepatic or hematological organ systems, which might impair the ability to complete this study or could interfere with determination of causality of any adverse effects experienced in this study, or which require treatment that could interact with study treatment.
- Have received treatment with any PARP inhibitors (i.e., Olaparib) or with any platinum based anti-neoplastic drugs.
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
The following procedures will be performed during the study, over the 10 visits at the clinic in the period of approximately 5 months: o Patients will receive 2 doses of TLX591 2 weeks apart. Doses are administered intravenously over approximately 15 minutes. the dosage of the intravenous injections will be 76 mCi each. Patients will attend the PETCT department at Mercy Radiology to receive the therapy. o Laboratory investigations (haematology, biochemistry, coagulation, and urinalysis). o Measurement of vital signs (Blood pressure Measurement , respiratory rate, heart rate, and body temperature). o Electrocardiogram o Blood tests will be performed periodically after each therapy. o During the months after therapy, we will contact patients to ask about their well-being, monitor any early or late symptoms or problems with therapy and ask to assess their pain. o Imaging (68Ga-PSMA PET/CT and, if necessary 18FDG PET/CT], and whole-body CT. 68Ga-PSMA PET/CT will be conducted at screening and 35 days post 1 dose of TLX591. Patients undergoing 68Ga-PSMA PET will receive both 68 GaPSMA tracer and contrast. Typically they receive a dose of at least 110MBq of 68Ga-PSMA but no more than 250MBq. The dosage is decided based on clinical judgement of the radiologist. Where there is no contraindication patients will receive 50mls of Contrast 15 minutes before the scan then 90mls during the scan. The Contrast used is Omnipaque350. If needed patients will also undergo 18FDG PET/CT. this would typically happen at screening, and it will depend on if the patients has had a scan done recently for their regular treatment. They will receive between 220MBq and 350MBq of the tracer 18FDG. The dosage is decided based on weight. Patients Typically receive around 80 mls of Contrast. We ask our patients to expect PET/CT appointments to last around 2.5 hours, however actual scan time is around 20 minutes. o SPECT/CT scans will be performed after administration of the radioligand therapy, at one day, four days and seven days following each treatment to assess the dose of radiation delivered to the tumour. No tracer is administered for this scan. This appointment typically lasts 1hour. Radiology technologists will perform all PET/CTs and SPECTs under the supervision of a radiologist. Images will be interpreted by 2 radiologists. The Imaging tests are 68Ga-PSMA PET/CT, 18FDG PET/CT and SPECT/CT. They are all different types of scans that require patients to lay still on a bed while they go through the scanner. The length of time of when they are on the scanner varies as described above. However eligible patients will be familiar with these scans as they already had at least 2 cycles of a similar therapy called lutetium PSMA. The first 2 patients will be enrolled at least 2 weeks apart and may be asked to have extra blood tests if clinically indicated Participation in the trial will involve exposure to radiation for therapy and for imaging. The dose of radiation patients receive will be the same as the therapy dose delivered in other studies of this agent. Patients will be advised regarding the safety precautions required during the short time that they are radioactive. There are risks involved with this type of radiation therapy to the function of your marrow, which makes blood cells and to kidney function. Patients are closely monitored for these effects and a a management plan is in place to treat/ minimize these effects. The dose patients will receive will be the minimum dose required for an adequate treatment effect. This dose of radiation will mostly target tumour tissue.
Locations(1)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12623000216617