A Randomised study comparing Lutetium-177 versus Apalutamide/Enzalutamide/Abiraterone, in metastatic Hormon Sensitive Prostate Cancer in PSMA positive patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Västerbotten, Umea University

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

28 Feb 2024 → ongoing

Decision date (initial)

2023-05-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this trial is to demonstrate superiority in progression free survival for 177Lu-PSMA-I&T versus Apalutamide/Enzalutamide/Abiraterone Acetate. (Radiographic, clinical, or PSA progression-free survival).

Secondary objectives 6

1. To evaluate and compare disease specific survival
2. To evaluate and compare response evaluation criteria in Solid tumours (RECIST)
3. To evaluate and compare time to first symptomatic skeletal event (SSE)
4. To evaluate and compare overall survival
5. To evaluate and compare PSA response
6. To evaluate and compare Safety Quality of Life (FACT-P-T)

Conditions and MedDRA coding

Prostate cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Histological or cytological proven prostate adenocarcinoma
2. Age ≥ 18 years
3. ECOG 0- 2
4. Estimated survival ≥ 3 months
5. Not eligible for triple therapy with Docetaxel
6. WBC 2000/mm3, neutrophils ≥1500/mm3, platelets ≥100,000/mm3
7. Satisfactory liver function: bilirubin, transaminases ≤ 1.5 times the upper limit of normal.
8. 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)
9. Patient information and signature of informed consent
10. Metastatic HSPC with measurable or evaluable disease
11. Patients must have evidence of PSMA-positive disease as seen on a [18F]PSMA-1007 or [68]Ga-gozetotide PET/CT scan
12. 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 16

1. Cardiovascular disease (severe symptomatic coronary artery disease, congenital heart failure, class 3 and 4 of the NYHA)
2. 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)
3. Active infection or other serious underlying pathology that could prevent patients from receiving treatment
4. History of cancer within 5 years before inclusion in the study other than basal cell or squamous cell skin cancer adequately treated
5. Brain metastases, uncontrolled symptomatic or asymptomatic
6. Patient participating in another clinical trial protocol with a molecule during this experimental study or treated four weeks prior to randomization.
7. Systemic treatment with high dose steroids
8. 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.
9. Prior treatment with ADT, Bicalutamide or Abiraterone acetate
10. Prior treatment with second generation anti-androgen
11. Prior treatment with chemotherapy
12. Prior treatment with radiopharmaceutical agents for prostate cancer
13. Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
14. Concurrent treatment with drugs decreasing the seizure threshold and/or cause seizure
15. Uncontrolled hypertension (systolic bloodpressure >160 mmHg or diastolic blood pressure >100 mmHg)
16. Subjects with hypersensitivity or contraindications to Apalutamide, Enzalutamide and/or Abiraterone acetate, according to the SmPC, should not be included in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate progression free survival between the two treatment arms (radiographic, clinical, or prostate-specific antigen [PSA] progression-free survival). That is, time from start of treatment until signs of progressive disease. Where progression is defined according to Prostate Cancer Working Group 3(PCWG3) and RECIST v 1.1.

Secondary endpoints 5

1. To evaluate and compare between the two treatment arms, time from start of treatment to death (disease specific and overall survival)
2. To evaluate and compare between the two treatment arms, Objective response rate: Radiological and PSA response rate is evaluated at week 14 from start with study drugs according to PCWG3 and RECIST 1.1
3. To evaluate and compare between the two treatment arms, time to first symptomatic skeletal event (SSE)
4. To evaluate and compare between the two treatment arms, Safety Quality of Life will be assested using FACT-P-T and BPI-SF
5. Evaluate toxic effect of dose on normal tissue and tumor in the experimental arm.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Västerbotten

Sponsor organisation

Region Västerbotten

Address

Koksvagen 11, Alidhem Alidhem

City

Umea

Postcode

907 37

Country

Sweden

Scientific contact point

Organisation

Region Västerbotten

Contact name

Martin Hellström

Public contact point

Organisation

Region Västerbotten

Contact name

Martin Hellström

Umea University

Sponsor organisation

Umea University

Address

Universitetstorget 4, Alidhem Alidhem

City

Umea

Postcode

907 36

Country

Sweden

Public contact point

Organisation

Umea University

Contact name

Anders Widmark

Sponsor responsibilities

Article 77 compliance

Region Västerbotten

Contact point sponsor

Region Västerbotten

Article 77 implementation

Region Västerbotten

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications