A Randomised, Open Label, Phase III, Multicenter, 2-arm study comparing 177Lu-PSMA-I&T versus Apalutamide/Enzalutamide/Abiraterone, in metastatic Hormon Sensitive Prostate Cancer Patients receiving castration treatment
- Trial ID
- 2022-500570-33-00
- Protocol
- Lut-AEA
- Sponsor
- Region Vaesterbotten
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this trial is to demonstrate the superiority of **progression-free survival** for 177Lu-PSMA-I&T compared to Apalutamide, Enzalutamide, or Abiraterone Acetate in patients with metastatic hormone-sensitive **prostate cancer**. This is clinically relevant as progression-free survival is a critical endpoint in assessing the efficacy of cancer treatments, indicating the length of time during and after treatment that a patient lives with the disease without it worsening.
Secondary objectives include:
- Evaluating and comparing disease-specific survival.
- Assessing response evaluation criteria in solid tumors (RECIST).
- Determining the time to the first symptomatic skeletal event (SSE).
- Comparing overall survival rates.
- Evaluating PSA response.
- Assessing safety and quality of life using the FACT-P-T scale.
Participants
The clinical trial focuses on **prostate cancer** and involves a study population exclusively composed of male subjects. The age range of participants is 18 years and older, with no upper age limit specified. Participants are required to have a histologically or cytologically confirmed diagnosis of prostate adenocarcinoma and must exhibit metastatic hormone-sensitive prostate cancer (HSPC) with measurable or evaluable disease. The trial does not include a vulnerable population. Participants must demonstrate satisfactory liver and renal function, as well as adequate hematological parameters. The trial population was selected based on specific inclusion criteria, including evidence of PSMA-positive disease on a PET/CT scan and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Lifestyle considerations such as the use of contraception are required for participants with fertile female partners. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed as a **randomized**, open-label, Phase III, multicenter study comparing the efficacy of **177Lu-PSMA-I&T** versus **apalutamide**, **enzalutamide**, or **abiraterone acetate** in patients with metastatic hormone-sensitive **prostate cancer**. The primary objective is to demonstrate superiority in progression-free survival for 177Lu-PSMA-I&T compared to the other treatments. The trial will evaluate radiographic, clinical, or PSA progression-free survival, with progression defined according to the Prostate Cancer Working Group 3 (PCWG3) and RECIST v1.1 criteria. Secondary endpoints include overall survival, objective response rate, time to first symptomatic skeletal event, and safety quality of life assessments.
The trial is expected to commence recruitment on January 1, 2024, and conclude by October 31, 2029. Participants will be involved for a maximum treatment period of 240 weeks, depending on the assigned treatment arm. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. Participants must meet specific inclusion criteria, such as histologically confirmed prostate adenocarcinoma, evidence of PSMA-positive disease, and an ECOG performance status of 0-2. Conditions for early termination from the study include disease progression, unacceptable toxicity, or withdrawal of consent.
Participants will be randomly assigned to receive either 177Lu-PSMA-I&T or one of the comparator drugs, with treatments administered according to the respective dosing schedules. The trial will ensure rigorous monitoring of safety and efficacy, with data collected at specified intervals to evaluate the primary and secondary endpoints. The study's design and methodology aim to provide robust evidence on the comparative effectiveness of these treatments in improving outcomes for patients with metastatic hormone-sensitive prostate cancer.
Treatment
The clinical trial involves the administration of **[177Lu]PSMA-I&T**, a **solution for injection** containing the active substance **177LU-PSMA-I&T**. This radiopharmaceutical is administered intravenously with a maximum daily dose of 8.14 GBq and a total dose not exceeding 56.98 GBq over a treatment period of up to 36 weeks. The primary objective is to evaluate its efficacy in metastatic hormone-sensitive prostate cancer patients.
**Xtandi** (enzalutamide) is provided as **40 mg film-coated tablets**. The maximum daily dose is 160 mg, administered orally. The treatment duration can extend up to 240 weeks. Enzalutamide acts as a comparator in the study, serving as a standard hormone therapy.
**ABIRATERONE ACETATE** is another comparator, available as **film-coated tablets**. The oral administration involves a maximum daily dose of 1000 mg, with a treatment period of up to 240 weeks. It is used in conjunction with hormone therapy.
**Erleada** (apalutamide) is administered as **60 mg film-coated tablets**. The maximum daily dose is 240 mg, taken orally, with a treatment duration of up to 240 weeks. Apalutamide is also part of the hormone therapy regimen in the trial.
**DEXAMETHASONE** is used as an **antiemetic** in the trial, provided in **tablet form**. The maximum daily dose is 2 mg, administered orally, with a treatment period of up to 84 weeks.
**METOCLOPRAMIDE HYDROCHLORIDE** is another antiemetic, available in **tablet form**. It is administered orally with a maximum daily dose of 30 mg, over a treatment period of up to 84 weeks.
**ONDANSETRON** is provided as **tablets** for antiemetic purposes. The oral administration involves a maximum daily dose of 24 mg, with a treatment period of up to 84 weeks.
**BETAMETHASONE** is also used as an antiemetic, available in **tablet form**. The maximum daily dose is 2 mg, administered orally, with a treatment period of up to 84 weeks.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the evaluation of **progression-free survival** (PFS) between the two treatment arms: 177Lu-PSMA-I&T and Apalutamide/Enzalutamide/Abiraterone Acetate. PFS is defined as the time from the start of treatment until signs of progressive disease, with progression determined according to the Prostate Cancer Working Group 3 (PCWG3) and RECIST v1.1 criteria. Secondary endpoints include the time from the start of treatment to death (both disease-specific and overall survival), objective response rate evaluated at week 14, time to first symptomatic skeletal event (SSE), and safety quality of life assessed using FACT-P-T and BPI-SF. Additionally, the toxic effect of the dose on normal tissue and tumor in the experimental arm will be evaluated.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Histological or cytological proven prostate adenocarcinoma
- Age ≥ 18 years
- ECOG 0- 2
- Estimated survival ≥ 3 months
- Not eligible for triple therapy with Docetaxel
- WBC 2000/mm3, neutrophils ≥1500/mm3, platelets ≥100,000/mm3
- Satisfactory liver function: bilirubin, transaminases ≤ 1.5 times the upper limit of normal.
- Satisfactory renal function: Serum creatinine <1.5 x ULN (150 mmol/l). If creatinine 1.0 – 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance >60 mL/min are accepted in the study. (For calculation see https://www.qxmd.com/calculate-online/nephrology/ckd-epi-egfr)
- Patient information and signature of informed consent
- Metastatic HSPC with measurable or evaluable disease
- Patients must have evidence of PSMA-positive disease as seen on a [18F]PSMA-1007 or [68]Ga-gozetotide PET/CT scan
- Patients included in the study that have fertile female partners must use adequate contraception, i.e. condom, within their relationship from start of the trial until 3 months after the last dose
Exclusion Criteria
- Cardiovascular disease (severe symptomatic coronary artery disease, congenital heart failure, class 3 and 4 of the NYHA)
- Inadequate organ and bone marrow function as evidenced by: Hemoglobin <10.0 g/dL Absolute neutrophil count <1.5 x 10^9/L, Platelet count <100 x 10^9/L, AST and/or ALT >1.5 x ULN; Total bilirubin >1.5 x ULN, Serum creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded (see http://www.qxmd.com/calculate-online/nephrology/ckd-epi-egfrfor for calculation)
- Active infection or other serious underlying pathology that could prevent patients from receiving treatment
- History of cancer within 5 years before inclusion in the study other than basal cell or squamous cell skin cancer adequately treated
- Brain metastases, uncontrolled symptomatic or asymptomatic
- Patient participating in another clinical trial protocol with a molecule during this experimental study or treated four weeks prior to randomization.
- Systemic treatment with high dose steroids
- Any severe acute or chronic medical condition which would impair the ability of the patient to participate to the study or interfere with interpretation of study results, or patient unable to comply with the study procedures.
- Prior treatment with ADT, Bicalutamide or Abiraterone acetate
- Prior treatment with second generation anti-androgen
- Prior treatment with chemotherapy
- Prior treatment with radiopharmaceutical agents for prostate cancer
- Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
- Concurrent treatment with drugs decreasing the seizure threshold and/or cause seizure
- Uncontrolled hypertension (systolic bloodpressure >160 mmHg or diastolic blood pressure >100 mmHg)
- Subjects with hypersensitivity or contraindications to Apalutamide, Enzalutamide and/or Abiraterone acetate, according to the SmPC, should not be included in the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Sweden | Recruiting | 01 Jan 2024 | 844 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Xtandi - 40 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 160 | 240 | PRD5512210 |
ABIRATERONE ACETATE | Comparator | — | ORAL | 1000 | 240 | SUB31647 |
Erleada 60 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 240 | 240 | PRD6957689 |
DEXAMETHASONE | Other | — | ORAL | 2 | 84 | SUB07017MIG |
METOCLOPRAMIDE HYDROCHLORIDE | Other | — | ORAL | 30 | 84 | SUB03271MIG |
ONDANSETRON | Other | — | ORAL | 24 | 84 | SUB09445MIG |
BETAMETHASONE | Other | — | ORAL | 2 | 84 | SUB05797MIG |
[177Lu]PSMA-I&T | Test | SOLUTION FOR INJECTION | SOLUTION FOR INJECTION | 8.14 | 36 | PRD10206695 |