Metastasis-directed Therapy for Oligorecurrent Prostate Cancer (SPARKLE)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT05352178 |
|
Recruitment Status :
Recruiting
First Posted : April 28, 2022
Last Update Posted : June 10, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Prostate Cancer Prostate Cancer Recurrent Prostate Cancer Metastatic Metastatic Cancer Oligometastatic Disease Oligometastasis Hormone Sensitive Prostate Cancer | Other: Radiotherapy (SBRT) and/or surgery (metastasectomy) Drug: Androgen deprivation therapy Drug: Androgen receptor targeted therapy | Phase 3 |
Metastasis-directed therapy (MDT) has broadened the therapeutic window in patients presenting with oligorecurrent prostate cancer as it postpones the initiation of palliative androgen deprivation therapy (pADT) and its substantial side-effects for several years. Also from a biological point of view, this might be beneficial as the (early) use of ADT promotes the development of the lethal castrate-resistant state, whereby metastatic progression is driven by androgen-independent pathways. Metastasis-directed therapy with stereotactic body radiotherapy (SBRT) or surgery has shown to be able to eradicate metastases with a significant advantage concerning the pADT-free survival compared to active surveillance. And the combination of SBRT with palliative systemic treatment significantly improved overall survival (OS) when compared tot systemic treatment alone.
One of the largest retrospective analyses (191 patients) on MDT for oligorecurrent prostate cancer has been conducted previously at UZ Leuven (doi: 10.3390/cancers12082271). Estimated median pADT-free survival was 66 months and estimated median mCRPC-free survival was not reached, but 83% of patients were still free of mCRPC at 10 years.
The addition of ADT to primary radiotherapy for intermediate of high risk prostate cancer or to salvage radiotherapy has shown to improve overall survival. Within the context of SBRT for oligorecurrent disease it is not yet known whether the addition of a certain period of ADT prolongs CRPC-free survival and if so, what should be the optimal duration of this ADT administration. Moreover, the addition of an androgen receptor targeted agent (ARTA) to ADT in men with metastatic hormone sensitive prostate cancer and a treated primary tumor resulted in significantly improved clinical outcomes, also in low-volume metastatic disease.
In this clinical trial the aim is to investigate whether the addition of short-term ADT during 1 month or short-term ADT during 6 months together with an ARTA to 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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 873 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Randomized, three-arm, phase III trial |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | a New Spark in Treating Oligorecurrent Prostate Cancer: Adding Systemic Treatment to Stereotactic Body Radiotherapy or Metastasectomy: Key to Long-lasting Event-free Survival? |
| Actual Study Start Date : | April 20, 2022 |
| Estimated Primary Completion Date : | April 25, 2027 |
| Estimated Study Completion Date : | April 25, 2032 |
| Arm | Intervention/treatment |
|---|---|
|
Active Comparator: MDT alone
Metastasis-directed therapy alone
|
Other: Radiotherapy (SBRT) and/or surgery (metastasectomy)
Metastasis-directed therapay (surgery and/or radiotherapy) as treatment for oligorecurrent lesions |
|
Experimental: MDT + 1 month of ADT
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)
Metastasis-directed therapay (surgery and/or radiotherapy) as treatment for oligorecurrent lesions Drug: Androgen deprivation therapy 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 |
|
Experimental: MDT + 6 months of ADT + anzalutamide
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)
Metastasis-directed therapay (surgery and/or radiotherapy) as treatment for oligorecurrent lesions Drug: Androgen deprivation therapy 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 Drug: Androgen receptor targeted therapy Enzalutamide |
- Poly-metastatic free survival (PMFS) [ Time Frame: up to 5 years after MDT ]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.
- Metastatic castration-refractory prostate cancer free survival (mCRPC-FS) [ Time Frame: up to 5 years after MDT ]mCRPC-FS will be calculated from the last day of MDT until the first day of diagnosis of castration-resistant prostate cancer (CRPC). CRPC is defined according to the contemporary EAU-guidelines as the time to biochemical and/or clinical progression at castrate testosterone levels (< 50 ng/dl). Biochemical progression is defined as three consecutive PSA rises (1 week interval), of which at least 2 rises with a PSA level of > 2 ng/ml and a rise of 50% above the nadir PSA level
- Biochemical progression-free survival (bPFS) [ Time Frame: up to 5 years after MDT ]bPFS will be calculated from the last day of MDT until the first day of biochemical relapse (BcR). BcR is defined as three consecutive PSA rises (1 week interval), of which at least 2 rises with a PSA level of > 2 ng/ml and a rise of 50% above the nadir PSA level.
- Clinical progression free survival (cPFS) [ Time Frame: up to 5 years after MDT ]
cPFS will be calculated from the last day of MDT until the first day of progression (local, nodal or metastatic) on PSMA PET-CT or PSMA PET-MRI. Imaging is performed in case of BcR, defined as above. Progression on PSMA PET-CT or PSMA PET-MRI will be defined as in the consensus statements on PSMA PET-CT or PSMA PET-MRI response assessment criteria in prostate cancer:
- the appearance of 2 or more new PSMA PET-CT or PSMA PET-MRI lesions or increase of uptake or tumor PET volume of at least 30%.
- OR the appearance of 1 new lesion with a high suspicion on PSMA PET-CT or PSMA PET-MRI
- Cancer Specific Survival (CSS) [ Time Frame: up to 10 years after MDT ]Cancer specific survival (CSS) will be calculated from last day of treatment until PCa death.
- Overall Survival (OS) [ Time Frame: up to 10 years after MDT ]Overall survival (OS) will be calculated from last day of treatment until death from any cause.
- Acute and late toxicity scoring [ Time Frame: up to 5 years after MDT ]Acute and late toxicity as a result of radiotherapy will be scores using the Common Toxicity Criteria Version 5.0 (30).
- Quality of life (QOL) [ Time Frame: up to 5 years after MDT ]Quality of life scoring using the EORTC QLQ-C30 supplement with QLQ-PR25. We will assess the quality-of-life-years with the EuroQOL classification system (EQ-5D-5L). Assessments are planned at baseline, last day of treatment, and during follow-up consultation at month M1, M3, M6, M12 and M24
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Gender Based Eligibility: | Yes |
| Gender Eligibility Description: | Male |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
- Patients must be presented at the multidisciplinary board meeting and the inclusion in the trial needs approval by this board.
- Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
- 2. 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.
Exclusion Criteria:
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05352178
| Contact: Kato Rans, MD | 003216340110 | kato.rans@uzleuven.be | |
| Contact: Gert De Meerleer, MD, PhD | 003216347600 | gert.demeerleer@uzleuven.be |
| Belgium | |
| University Hospitals Leuven | Recruiting |
| Leuven, Belgium | |
| Contact: Kato Rans, MD 003216340110 kato.rans@uzleuven.be | |
| Contact: Gert De Meerleer, MD, PhD 003216347600 gert.demeerleer@uzleuven.be | |
| Principal Investigator: Gert De Meerleer, MD, PhD | |
| Responsible Party: | Universitaire Ziekenhuizen KU Leuven |
| ClinicalTrials.gov Identifier: | NCT05352178 |
| Other Study ID Numbers: |
S65935 2022-000066-18 ( EudraCT Number ) |
| First Posted: | April 28, 2022 Key Record Dates |
| Last Update Posted: | June 10, 2022 |
| Last Verified: | May 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
|
Androgen deprivation therapy Androgen receptor targeted agent Stereotactic body radiation therapy Metastasis-directed therapy |
|
Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Genital Diseases Urogenital Diseases Prostatic Diseases Male Urogenital Diseases Ascorbic Acid Methyltestosterone Androgens |
Estrogens, Conjugated (USP) Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Vitamins Micronutrients Estrogens Antineoplastic Agents, Hormonal Antineoplastic Agents Anabolic Agents |