Ignite Creation Date:
2024-05-11 @ 8:30 AM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06401980
Status:
RECRUITING
Last Update Posted:
2024-05-07
First Post:
2024-05-02
Brief Title:
Darolutamide in Metastatic Castration-Resistant Prostate Cancer mCRPC
Sponsor:
Swiss Group for Clinical Cancer Research
Organization:
Swiss Group for Clinical Cancer Research
Study Overview
Official Title:
Addition of Darolutamide to First Line Treatment of Metastatic Castration-Resistant Prostate Cancer mCRPC a Randomized Open Label Phase II Trial
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Despite improvements in treatment metastatic prostate cancer remains incurable especially in the case of pretreated metastatic castration-resistant disease mCRPC where treatment options are limited leading to an unmet need The paradigm shift in the treatment of metastatic hormone-sensitive prostate cancer mHSPC has affected the treatment landscape for mCRPC patients Many have already received androgen deprivation therapy ADT and androgen receptor pathway inhibitors ARPI making first-line mCRPC treatment challenging
The Swiss Group for Clinical Cancer Research SAKK has shown in previous studies that maintenance treatment with an ARPI such as darolutamide can improve radiographic progression-free survival rPFS in pretreated mCRPC patients In the SAKK 0816 trial darolutamide maintenance was found to prolong PFS compared to placebo especially in patients who responded well to prior ARPI treatment
Based on these findings the hypothesis is that continued AR-pathway blockade with darolutamide initiated in patients progressing from mHSPC to mCRPC on ARPI treatment can improve outcomes when added to standard first-line mCRPC therapy and continued as maintenance The proposed study aims to evaluate the efficacy of darolutamide combined with physician-choice standard of care including taxane chemotherapy olaparib radium 223 or LuPSMA followed by maintenance therapy on rPFS for patients in the first-line setting of mCRPC
The Swiss Group for Clinical Cancer Research SAKK has shown in previous studies that maintenance treatment with an ARPI such as darolutamide can improve radiographic progression-free survival rPFS in pretreated mCRPC patients In the SAKK 0816 trial darolutamide maintenance was found to prolong PFS compared to placebo especially in patients who responded well to prior ARPI treatment
Based on these findings the hypothesis is that continued AR-pathway blockade with darolutamide initiated in patients progressing from mHSPC to mCRPC on ARPI treatment can improve outcomes when added to standard first-line mCRPC therapy and continued as maintenance The proposed study aims to evaluate the efficacy of darolutamide combined with physician-choice standard of care including taxane chemotherapy olaparib radium 223 or LuPSMA followed by maintenance therapy on rPFS for patients in the first-line setting of mCRPC
Detailed Description:
Metastatic prostate cancer remains incurable despite several major improvements in the treatment In the case of pretreated metastatic castration-resistant disease mCRPC the options remain scarce and there is still an unmet need in this patient population
For the majority of patients with metastatic hormone-sensitive prostate cancer mHSPC the combination of androgen deprivation ADT and ARPI or even a triplet treatment with ADT docetaxel and darolutamide or abiraterone has become standard of care However when patients become metastatic castration resistant mCRPC over time a change of systemic treatment is necessary and thus this paradigm switch in treatment of mHSPC has had a major impact on treatment of mCRPC patients Many patients developing metastatic castration-resistant disease these days have not only received ADT but also an ARPI and in some cases also docetaxel Therefore the treatment options in the first line setting of mCRPC are restricted and the outcome is poorer compared to the past Improvement of first line mCRPC is an important unmet clinical need
The SAKK has demonstrated in two earlier studies that maintenance treatment with an ARPI orteronel in SAKK 0811 or darolutamide in SAKK 0816 can improve radiographic progression-free survival in pretreated mCRPC patients after ARPI andor taxane based This maintenance concept could be introduced more generally in the first line setting of mCRPC
In the SAKK 0816 trial darolutamide maintenance was shown to prolong progression-free survival PFS compared to placebo in patients with mCRPC who had received prior ARPI and whose disease did not progress during taxane therapy This benefit was more pronounced in patients with prior response to ARPI
Taken together it is hypothesized that the continued AR-pathway blockade with darolutamide in patients progressing from mHSPC to mCRPC on ARPI treatment can improve outcome when it is added to a standard first line mCRPC therapy and then continued as maintenance SAKK proposes to add the ARPI darolutamide to standard first line mCRPC treatment consisting of either taxane chemotherapy docetaxel or cabazitaxel olaparib radium 223 or LuPSMA The choice of standard of care treatment is up to the investigator respecting the country specific approvals Darolutamide will be given concomitantly with the chosen first line treatment and will be continued as maintenance afterwards until radiographic progression
For the majority of patients with metastatic hormone-sensitive prostate cancer mHSPC the combination of androgen deprivation ADT and ARPI or even a triplet treatment with ADT docetaxel and darolutamide or abiraterone has become standard of care However when patients become metastatic castration resistant mCRPC over time a change of systemic treatment is necessary and thus this paradigm switch in treatment of mHSPC has had a major impact on treatment of mCRPC patients Many patients developing metastatic castration-resistant disease these days have not only received ADT but also an ARPI and in some cases also docetaxel Therefore the treatment options in the first line setting of mCRPC are restricted and the outcome is poorer compared to the past Improvement of first line mCRPC is an important unmet clinical need
The SAKK has demonstrated in two earlier studies that maintenance treatment with an ARPI orteronel in SAKK 0811 or darolutamide in SAKK 0816 can improve radiographic progression-free survival in pretreated mCRPC patients after ARPI andor taxane based This maintenance concept could be introduced more generally in the first line setting of mCRPC
In the SAKK 0816 trial darolutamide maintenance was shown to prolong progression-free survival PFS compared to placebo in patients with mCRPC who had received prior ARPI and whose disease did not progress during taxane therapy This benefit was more pronounced in patients with prior response to ARPI
Taken together it is hypothesized that the continued AR-pathway blockade with darolutamide in patients progressing from mHSPC to mCRPC on ARPI treatment can improve outcome when it is added to a standard first line mCRPC therapy and then continued as maintenance SAKK proposes to add the ARPI darolutamide to standard first line mCRPC treatment consisting of either taxane chemotherapy docetaxel or cabazitaxel olaparib radium 223 or LuPSMA The choice of standard of care treatment is up to the investigator respecting the country specific approvals Darolutamide will be given concomitantly with the chosen first line treatment and will be continued as maintenance afterwards until radiographic progression
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None