Surgical treatment with or without apalutamide in subjects with high risk prostate cancer who are candidates for radical prostatectomy and staged as oligometastatic with PSMA-PET (STAPLE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universita' Degli Studi Di Torino

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Jul 2024 → ongoing

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515049-41-00

EudraCT number

2022-002844-37

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine if treatment with apalutamide plus ADT after RP results in an improvement in RPFS based on PSMA PET/CT, as compared to ADT alone

Secondary objectives 3

1. To characterize the safety profile of treatment with apalutamide plus ADT after RP
2. To explore measures of efficacy
3. To evaluate treatment-related symptoms / tolerability

Conditions and MedDRA coding

metastatic prostate cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. ≥ 18 years of age, < 80 years of age
2. Signed informed consent form (ICF) indicating that the subject understands the purpose and procedures required for the study and is willing to participate in the study; subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol
3. Histologically confirmed adenocarcinoma of the prostate
4. High-risk disease defined by a total Gleason Sum Score ≥ 4+4 (=Grade Groups [GG] 4-5), PSA >20 ng/ml, or ≥cT2c based on digital rectal examination or ≥cT3 or cN+ based on preoperative imaging
5. Conventional imaging negative for metastases
6. Presence of low volume metastatic disease at pre-surgery PSMA PET/CT. The metastatic burden is classified according to the definition used in the CHARTEED trial applied to PSMA PET/CT, where high metastatic burden was defined as four or more bone metastases with one or more outside the vertebral bodies or pelvis, or visceral metastases, or both; all other assessable patients were considered to have low metastatic burden
7. Candidate to RP with PLND
8. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
9. Adequate organ function
10. Able to receive ADT for at least 18 months, based on cardiovascular risk assessment and the investigator’s assessment
11. Be able to swallow whole study drug tablets

Exclusion criteria 14

1. Distant metastasis based on conventional imaging (CT scan or bone scintigraphy). Nodal disease below the iliac bifurcation (clinical stage N1 at CT scan) is not an exclusion criterion.
2. Prior hormonal treatment (GnRHa, agonist or antagonist)
3. Prior bilateral orchiectomy
4. History of prior systemic or local therapy for prostate cancer, including pelvic radiation and whole gland or focal ablative modalities for prostate cancer
5. Use of any investigational agent ≤4 weeks prior to RP or any therapeutic procedure for prostate cancer at any time
6. Major surgery ≤4 weeks prior to RP
7. Any of the following within 12 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary
8. Human immunodeficiency virus-positive subjects with 1 or more of the following: (1) not receiving highly active antiretroviral therapy; (2) had a change in antiretroviral therapy within 6 months of the start of screening; (3) receiving antiretroviral therapy that may interfere with study drug (consult Sponsor for review of medication prior to enrolment); (4) CD4 count <350 at screening; (5) AIDS-defining opportunistic infection within 6 months of start of screening; (6) active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction
9. History of seizure; any condition that may predispose to seizure
10. Patients taking any prohibited medications (as reported in the protocol) should not be included
11. Gastrointestinal conditions affecting absorption
12. Known or suspected contraindications or hypersensitivity to apalutamide, GnRHa or any of the components of the formulations
13. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject
14. Active malignancies other than prostate cancer. The only allowed exceptions are: non-muscle invasive bladder cancer (NMIBC); skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; breast cancer (adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence); malignancy that is considered cured with minimal risk of recurrence.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Radiological progression-free survival (RPFS), evaluated based on PSMA PET/CT

Secondary endpoints 3

1. Adverse events (AEs)
2. Biochemical progression-free survival (BPFS)* Progression-free survival 2 (PFS2) Time to castration-resistant PCa (CRPC) Percentage of subjects receiving postoperative radiotherapy Overall survival (OS)
3. Change from baseline over time in Expanded Prostate Cancer Index (EPIC-26) and EQ-5D-5L

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universita' Degli Studi Di Torino

Sponsor organisation

Universita' Degli Studi Di Torino

Address

Corso Bramante 88/90

City

Turin

Postcode

10126

Country

Italy

Scientific contact point

Organisation

Universita' Degli Studi Di Torino

Contact name

Marco Oderda

Public contact point

Organisation

Universita' Degli Studi Di Torino

Contact name

Marco Oderda

Locations

1 EU/EEA country · 11 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 15 files

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

Application history

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