Ignite Creation Date:
2024-05-06 @ 1:27 PM
Last Modification Date:
2024-10-26 @ 1:15 PM
Study NCT ID:
NCT04038502
Status:
RECRUITING
Last Update Posted:
2023-11-01
First Post:
2019-07-26
Brief Title:
Carboplatin or Olaparib for BRcA Deficient Prostate Cancer
Sponsor:
VA Office of Research and Development
Organization:
VA Office of Research and Development
Study Overview
Official Title:
An Open-label Multicenter Phase II Study to Compare the Efficacy of Carboplatin as First-line Followed by Second-line Olaparib Versus Olaparib as First-line Followed by Second-line Carboplatin in the Treatment of Patients With Castration Resistant Prostate Cancer Containing Homologous Recombination Deficiency
Status:
RECRUITING
Status Verified Date:
2024-09
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:
COBRA
Brief Summary:
This is an unblinded randomized clinical study comparing the efficacy of DNA damaging chemotherapy using carboplatin to standard of care therapy for patients who have metastatic castrate resistant prostate cancer This trial will use olaparib or carboplatin as initial therapy with crossover to the alternate or second-line drug after first progression for patients with tumors containing BARD1 BRCA1 BRCA2 BRIP1 CHEK1 FANCL PALB2 RAD51B RAD51C RAD51D or RAD54L inactivating mutations
Participants are randomized 11 and receive either carboplatin AUC 5 IV every 21 days first or olaparib taken orally 300 mg twice daily in 28 day cycles until intolerance complete response or progression by Prostate Cancer Working Group 3 PCWG3 criteria
Participants then crossover from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression whichever is first Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria and at least three weeks have elapsed since last administration of either carboplatin or olaparib Throughout the study safety and tolerability will be assessed Progression will be evaluated with bone scan CT of the abdomenpelvis or MRI and PSA as per PCWG3 criteria
Participants are randomized 11 and receive either carboplatin AUC 5 IV every 21 days first or olaparib taken orally 300 mg twice daily in 28 day cycles until intolerance complete response or progression by Prostate Cancer Working Group 3 PCWG3 criteria
Participants then crossover from the first-line therapy to the second-line therapy with the opposite study medication and receive treatment to intolerance or progression whichever is first Enrolled participants will be allowed to crossover to second line therapy if they continue to meet initial eligibility criteria and at least three weeks have elapsed since last administration of either carboplatin or olaparib Throughout the study safety and tolerability will be assessed Progression will be evaluated with bone scan CT of the abdomenpelvis or MRI and PSA as per PCWG3 criteria
Detailed Description:
Study General Trial Over-view
This study is designed to help better understand treatment options compared to standard therapies for patients who have targeted DNA repair mutations and metastatic castrate resistant prostate cancer mCRPC
Cancer therapies are aimed at finding a way to kill the cancer cells while causing minimal damage to normal non-cancer cells This often works because cancers cells grow faster than many normal cells many treatments are aimed at to take advantage of that difference One of the ways to do this is to damage the DNA of these more rapidly growing cells However if the cells have a way of repairing that damage then therapies may not work as well Some research shows that when specific changes or mutations occur in the genes involved with repairing DNA damage resulting cancers have responded well to drugs which damage DNA
Olaparib is known as a PARP inhibitor and is standard of care therapy for men with BRCA altered mCRPC Carboplatin is a synthetic antineoplastic agent which has been used in the treatment of solid tumors and BRCA related cancers When mutations occur in critical DNA-repair genes research has found that treatment with carboplatin is also effective
This research is being done to determine the response of mCRPC in patients with DNA repair mutations to treatment with olaparib compared to carboplatin This study will test whether giving one drug or the other a has a better response
Patients wishing to participate in this study are screened for safety and health eligibility before enrolling
This study is enrolling 100 male participants total from across the VAMC nationally who have the following
Metastatic castration-resistant prostate cancer mCRPC
Cancer that has gotten worse after any number of first-line treatments
Mutations in DNA-repair genes discovered as part of a patients routine care
Once eligibility is determined enrolled participants are randomized into one of two groups
Group A will start with carboplatin IV first given every 21 days then have the option to switch to the second treatment with olaparib taken daily orally with cycles of every 28 days
Group B will start with olaparib first taken orally with 28 day cycles then have the option to switch to the second treatment with carboplatin IV every 21 days
Both study drugs in this trial are currently FDA approved and are prescribed at the participating VAMC clinical sites per institutional guidelines Carboplatin given in IV is also given as prescribed at the participating VAMC and administered per institutional guidelines
Participants are monitored for health and body function cancer progression toxicity and life quality at every visit during the trial and at an end of treatment visit 28 days after completion of the trial or after withdrawal For participants who respond well to treatment during the trial additional treatment cycles may be added and the study can be extended Participants who experience intolerable toxicity cancer progression or whose doctors decide to change treatment will either be switched to the opposite study drug or withdrawn from the study
This important trial is designed to compare response rate and duration of response using carboplatin compared to olaparib in patients who have mCRPC which contains DNA repair gene mutations
This study is designed to help better understand treatment options compared to standard therapies for patients who have targeted DNA repair mutations and metastatic castrate resistant prostate cancer mCRPC
Cancer therapies are aimed at finding a way to kill the cancer cells while causing minimal damage to normal non-cancer cells This often works because cancers cells grow faster than many normal cells many treatments are aimed at to take advantage of that difference One of the ways to do this is to damage the DNA of these more rapidly growing cells However if the cells have a way of repairing that damage then therapies may not work as well Some research shows that when specific changes or mutations occur in the genes involved with repairing DNA damage resulting cancers have responded well to drugs which damage DNA
Olaparib is known as a PARP inhibitor and is standard of care therapy for men with BRCA altered mCRPC Carboplatin is a synthetic antineoplastic agent which has been used in the treatment of solid tumors and BRCA related cancers When mutations occur in critical DNA-repair genes research has found that treatment with carboplatin is also effective
This research is being done to determine the response of mCRPC in patients with DNA repair mutations to treatment with olaparib compared to carboplatin This study will test whether giving one drug or the other a has a better response
Patients wishing to participate in this study are screened for safety and health eligibility before enrolling
This study is enrolling 100 male participants total from across the VAMC nationally who have the following
Metastatic castration-resistant prostate cancer mCRPC
Cancer that has gotten worse after any number of first-line treatments
Mutations in DNA-repair genes discovered as part of a patients routine care
Once eligibility is determined enrolled participants are randomized into one of two groups
Group A will start with carboplatin IV first given every 21 days then have the option to switch to the second treatment with olaparib taken daily orally with cycles of every 28 days
Group B will start with olaparib first taken orally with 28 day cycles then have the option to switch to the second treatment with carboplatin IV every 21 days
Both study drugs in this trial are currently FDA approved and are prescribed at the participating VAMC clinical sites per institutional guidelines Carboplatin given in IV is also given as prescribed at the participating VAMC and administered per institutional guidelines
Participants are monitored for health and body function cancer progression toxicity and life quality at every visit during the trial and at an end of treatment visit 28 days after completion of the trial or after withdrawal For participants who respond well to treatment during the trial additional treatment cycles may be added and the study can be extended Participants who experience intolerable toxicity cancer progression or whose doctors decide to change treatment will either be switched to the opposite study drug or withdrawn from the study
This important trial is designed to compare response rate and duration of response using carboplatin compared to olaparib in patients who have mCRPC which contains DNA repair gene mutations
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CX-18-006 | OTHER_GRANT | None | None |
| 19-08 | OTHER | None | None |
| 01783 | OTHER | None | None |
| 01781 | OTHER | None | None |
| CX001963-01 | OTHER | Veterans Affairs CSRD | None |