Metastasis-directed Therapy for Oligorecurrent Prostate Cancer

NCT05352178 | Recruiting Phase 3

• 2 other identifiers: S659352022-000066-18
• Study Type: interventional
• Target: 873
• Locations: 1 country
• Sites: 1

Brief Summary

The aim is to investigate whether the addition of short-term androgen deprivation therapy (ADT) during 1 month or short-term ADT during 6 months together with an androgen receptor targeted therapy (ARTA) to metastasis-directed therapy (MDT) significantly prolongs poly-metastatic free survival (PMFS) and/or metastatic castration-refractory prostate cancer free survival (mCRPC-FS) in patients with oligorecurrent hormone sensitive prostate cancer.

Conditions

Prostate Cancer; Prostate Cancer Recurrent; Prostate Cancer Metastatic; Metastatic Cancer; Oligometastatic Disease; Oligometastasis; Hormone Sensitive Prostate Cancer

Keywords

Androgen deprivation therapy; Androgen receptor targeted agent; Stereotactic body radiation therapy; Metastasis-directed therapy

Outcome Measures

Primary Outcomes (1)

• Poly-metastatic free survival (PMFS)

  from the last day of MDT until the first day of poly-progression which is defined as the detection \> 5 new lesions at PSMA PET-CT or PSMA PET-MRI (+/- combined with MRI if needed to improve diagnostic accuracy). In case of poly-progression, pADT will be considered the standard-of-care. Other indications to start pADT are local progression of an irradiated site and/or or clinical symptoms caused by local progression. In all cases, the initiation of pADT will only be carried out after approval of the multidisciplinary tumor board. Any decision to start with pADT will be reported with date and specific reason. If recurrence occurs in 5 lesions or less a new MDT is proposed if technically feasible.

  up to 5 years after MDT

Secondary Outcomes (7)

• Metastatic castration-refractory prostate cancer free survival (mCRPC-FS)

  up to 5 years after MDT

• Biochemical progression-free survival (bPFS)

  up to 5 years after MDT

• Clinical progression free survival (cPFS)

  up to 5 years after MDT

• Cancer Specific Survival (CSS)

  up to 10 years after MDT

• Overall Survival (OS)

  up to 10 years after MDT

Study Arms (3)

MDT alone

ACTIVE COMPARATOR

Metastasis-directed therapy alone

Other: Radiotherapy (SBRT) and/or surgery (metastasectomy)

MDT + 1 month of ADT

EXPERIMENTAL

Metastasis-directed therapy plus one month of androgen deprivation therapy (gosereline 3.6 mg sc, leuproreline 7.5 mg sc, triptoreline 3.75 mg im)

Other: Radiotherapy (SBRT) and/or surgery (metastasectomy); Drug: Androgen deprivation therapy

MDT + 6 months of ADT + anzalutamide

EXPERIMENTAL

Metastasis-directed therapy plus 6 months of androgen deprivation therapy (gosereline 3.6 mg sc 1x/month or gosereline 10.8 mg sc or leuproreline 7.5 mg sc 1x/month or leuproreline 45 mg sc or triptoreline 3.75 mg im 1x/month or triptoreline 11.5 mg im 1x/3months or triptoreline 22.5 mg im) and enzalutamide (4 x 40 mg each day during 6 months )

Other: Radiotherapy (SBRT) and/or surgery (metastasectomy); Drug: Androgen deprivation therapy; Drug: Androgen receptor targeted therapy

Interventions

Radiotherapy (SBRT) and/or surgery (metastasectomy) OTHER

Metastasis-directed therapay (surgery and/or radiotherapy) as treatment for oligorecurrent lesions

MDT + 1 month of ADT; MDT + 6 months of ADT + anzalutamide; MDT alone

Androgen deprivation therapy DRUG

Arm B: gosereline 3.6 mg sc, leuproreline 7.5 mg sc, triptoreline 3.75 mg im Arm C: gosereline 3.6 mg sc 1x/month or gosereline 10.8 mg sc or leuproreline 7.5 mg sc 1x/month or leuproreline 45 mg sc or triptoreline 3.75 mg im 1x/month or triptoreline 11.5 mg im 1x/3months or triptoreline 22.5 mg im

MDT + 1 month of ADT; MDT + 6 months of ADT + anzalutamide

Androgen receptor targeted therapy DRUG

Enzalutamide

MDT + 6 months of ADT + anzalutamide

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven initial diagnosis of prostate adenocarcinoma
• Priory treated and controlled primary tumor
• Biochemical recurrence defined by prostate-specific antigen (PSA) values \>0,2 ng/ml (i.e., two consecutive increases) following radical prostatectomy + postoperative radiotherapy and a PSA value of 2 ng/ml above the nadir after high-dose RT.
• Oligorecurrent disease defined as a maximum of 5 extracranial metastases in any organ, diagnosed on PSMA PET-CT or PSMA PET-MRI reported according to the E-PSMA consensus guidelines for interpretation of PSMA-PET (26). Nodal (N1) disease can be included only when accompanied by M1a-c disease, provided that the total number of spots does not exceed 5.
• Serum testosterone level within normal range.
• WHO performance 0-2
• Age \>= 18 years old
• Absence of psychological, sociological or geographical condition potentially hampering compliance with study protocol.
• Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
• \. Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.

You may not qualify if:

• Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol
• Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial
• Participation in an interventional Trial with an investigational medicinal product (IMP) or device
• Serum testosterone level at castration level.
• PSA rise while on active treatment (LHRH-agonist, LHRH antagonist, anti-androgen, maximal androgen blockade, oestrogen)
• Presence of poly-metastatic disease, defined as more than 5 metastatic lesions.
• Active malignancy other than prostate cancer that could potentially interfere with the interpretation of this trial.
• Previous treatments (RT, surgery) or comorbidities rendering new treatment with SBRT impossible.
• Contra indications for intake of enzalutamide (seizure or any condition that may predispose to seizure; significant cardiovascular disease within the last three months including myocardial infarction, unstable angina, congestive heart failure, ongoing arrythmias of grade \> 2 or a thromboembolic event).
• Not able to understand the treatment protocol or sign informed consent.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

University Hospitals Leuven

Leuven, Belgium

RECRUITING

Related Publications (1)

• Rans K, Charlien B, Filip A, Olivier H, Julie DH, Cederic D, Herlinde D, Benedikt E, Karolien G, Annouschka L, Nick L, Kenneth P, Carl S, Koen S, Hans V, Ben V, Steven J, Gert M. SPARKLE: a new spark in treating oligorecurrent prostate cancer: adding systemic treatment to stereotactic body radiotherapy or metastasectomy: key to long-lasting event-free survival? BMC Cancer. 2022 Dec 12;22(1):1294. doi: 10.1186/s12885-022-10374-0.

  PMID: 36503429 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

Radiotherapy; Radiosurgery; Metastasectomy; Androgen Antagonists

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Kato Rans, MD

CONTACT

003216340110; kato.rans@uzleuven.be

Gert De Meerleer, MD, PhD

CONTACT

003216347600; gert.demeerleer@uzleuven.be

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, three-arm, phase III trial

Study Record Dates

• First Submitted: April 22, 2022
• First Posted: April 28, 2022
• Study Start: April 20, 2022
• Primary Completion (Estimated): April 25, 2027
• Study Completion (Estimated): April 25, 2032
• Last Updated: July 3, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)