Ignite Creation Date:
2024-05-06 @ 10:34 AM
Last Modification Date:
2024-10-26 @ 12:32 PM
Study NCT ID:
NCT03294694
Status:
TERMINATED
Last Update Posted:
2022-03-31
First Post:
2017-09-19
Brief Title:
Ribociclib PDR001 in Breast Cancer and Ovarian Cancer
Sponsor:
Dana-Farber Cancer Institute
Organization:
Dana-Farber Cancer Institute
Study Overview
Official Title:
A Phase 1 Study of the CDK46 Inhibitor Ribociclib LEE011 in Combination With the PD-1 Inhibitor PDR001 in Patients With Metastatic Hormone Receptor-positive Breast Cancer and Metastatic Ovarian Cancer
Status:
TERMINATED
Status Verified Date:
2022-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Safety Implications
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This clinical trial is studying the drug Ribociclib LEE011 in combination with an immunotherapy drug called PDR001 a therapy that uses the bodys own immune system to control cancer as a possible treatment for metastatic hormone-receptor-positive HR HER2-negative breast cancer in combination with fulvestrant or metastatic epithelial ovarian cancer
The names of the medications involved in this study are
Ribociclib LEE011
PDR001
Fulvestrant
The names of the medications involved in this study are
Ribociclib LEE011
PDR001
Fulvestrant
Detailed Description:
This research study is a Phase I clinical trial which tests the safety of an investigational combination of drugs LEE011 with PDR001 and tries to define the appropriate dose of the above combination of investigational drugs to use for further studies Investigational means that the intervention is being studied
The FDA the US Food and Drug Administration has approved LEE011 as a treatment for hormone receptor positive metastatic breast cancer
The FDA has not approved PDR001 as treatment for any type of cancer
The FDA has approved fulvestrant as a treatment for hormone receptor positive metastatic breast cancer
When given separately these medications work in different ways to try and stop cancer cells from growing and spreading
LEE011 is a drug designed to block certain proteins called cyclin-dependent kinases CDKs that are required for cells to divide These proteins may also control the ability of certain cancers to grow
PDR001 is an antibody Antibodies are proteins usually produced by the body that help protect against foreign matter such as bacteria and viruses PDR001 blocks a protein called PD-1 which is present on cells called T-lymphocytes which are involved in the immune response PDR001 is being tested to see if it will allow the bodys immune system to work against tumor cells Other studies have shown that blocking PD-1 may result in reduced tumor cell growth in a variety of solid tumors
Fulvestrant is an estrogen receptor antagonist that is indicated for the treatment of postmenopausal women with HR MBC
In this research study the investigators are looking for a safe and tolerable dose of LEE011 that can be given in combination with PDR001 for participants with metastatic hormone-receptor-positive HR HER2-negative breast cancer in combination with fulvestrant or metastatic epithelial ovarian cancer
ELIGIBILITY FOR COHORT A DOSE ESCALATION Ribociclib PDR001
Hormone receptor HR-positive HER2-negative metastatic breast cancer according to ASCO CAP Guidelines
Participants may have received any number of previous endocrinehormonal lines of therapy in the metastatic setting as long as the last dose is 14 days prior to registration
Participants may have received any number of prior lines of chemotherapy for advanced breast cancer as long as the last dose is 21 days prior to registration
Prior therapy with biologics and investigational drugs is allowed as long as the last dose is 21 days prior to registration
Prior CDK46 inhibition is allowed Participants who have had prior ribociclib must have received treatment at full-dose without any dose-reductions The last dose is required to be 21 days prior to registration
No prior PD1PDL1CTLA4 inhibitors
Participants may have received radiotherapy for palliative purposes but must have completed treatment 14 days prior to registration and not be experiencing grade 1 treatment related toxicities
Men are eligible as long as on a GnRH agonist for at least 6 weeks prior to study entry Men MUST remain on the GnRH agonist for the duration of protocol treatment
Evaluable or measurable disease by RECIST 11
Metastatic epithelial ovarian cancer fallopian tube or peritoneal cancer All histologies including serous mucinous endometrioid clear cell MMMTs and mix histologies and tumor grades are eligible
Must have received a first-line platinum-based therapy and have disease that is platinum-resistant
--- Platinum-resistant disease is defined as disease relapse within 2 to 6 months of prior platinum-based chemotherapy
There is no limit to the number of lines of prior chemotherapy biology or hormonal therapy regimens
No prior PD1PDL1CTLA4 inhibitors
Evaluable or measurable disease by RECIST 11
ELIGIBILITY FOR COHORT A DOSE EXPANSION Ribociclib PDR001
Metastatic epithelial ovarian cancer fallopian tube or peritoneal cancer All histologies including serous mucinous endometrioid clear cell MMMTs and mixed histologies and tumor grades are eligible
Must have received a first-line platinum-based chemotherapy regimen and have relapsed despite standard therapy
Must have received a first-line platinum-based therapy and have disease that is platinum-resistant
--- Platinum-resistant disease is defined as disease relapse within 2 to 6 months of prior platinum-based chemotherapy
There is no limit to the number of lines of prior chemotherapy biology or hormonal therapy regimens
Patients may have received any number of previous endocrine hormonal lines of therapy in the metastatic setting as long as the last dose is 14 days prior to first dose of study treatment
Prior therapy with biologics and investigational drugs is allowed as long as the last dose is 21 days prior to first dose of study treatment
No prior CDK46 inhibitors
No prior PD1PDL1CTLA4 inhibitors
Measurable disease by RECIST 11
Participants with accessible tumor lesions must be willing to undergo two research biopsies one prior to treatment initiation and one after 7 weeks of protocol therapy Participants who undergo an attempted on-treatment research biopsy and in whom inadequate tissue is obtained are still eligible to receive protocol therapy They will not be required to undergo a repeat research biopsy attempt If a biopsy-accessible participant has had a biopsy within 30 days of treatment initiation for clinical purposes they may choose to submit an archived specimen from this procedure instead
ELIGIBILITY FOR COHORT B SAFETY RUN-IN Ribociclib PDR001 Fulvestrant
Hormone receptor HR-positive HER2-negative metastatic breast cancer according to ASCO CAP Guidelines
Men are eligible as long as on a GnRH agonist for at least 6 weeks prior to study entry Men MUST remain on the GnRH agonist for the duration of protocol treatment
Women must be postmenopausal as defined as
-- Age 60 years or Age 45 with intact uterus and amenorrhea for 12 consecutive months or Follicle stimulating hormone FSH levels within postmenopausal range according to the ranges established by the testing facility or Premenopausal women who have been on a GnRH agonist for at least 6 weeks prior to study entry Women in this group MUST remain on the GnRH agonist for the duration of protocol treatment or Status post bilateral oophorectomy after adequate healing post-surgery
Evaluable or measurable disease by RECIST 11
Prior CDK46 inhibition is allowed Participants who have had prior ribociclib must have received treatment at full-dose without any dose-reductions The last dose is required to be 21 days prior to registration
Prior hormonal therapy
Prior therapy with Fulvestrant is allowed
Participants may have received any number of previous endocrinehormonal lines of therapy in the metastatic setting as long as the last dose is 14 days prior to registration
Participants may have received chemotherapy for advanced breast cancer as long as the last dose is 21 days prior to registration
Prior therapy with biologics and investigational drugs is allowed as long as the last dose is 21 days prior to registration
Participants may have received radiotherapy for palliative purposes but must have completed treatment 14 days prior to registration and not be experiencing grade 1 treatment related toxicities
ELIGIBILITY FOR COHORT B DOSE EXPANSION Ribociclib PDR001 Fulvestrant
Hormone receptor HR-positive HER2-negative metastatic breast cancer according to ASCO CAP Guidelines
Men are eligible as long as on a GnRH agonist for at least 6 weeks prior to study entry Men MUST remain on the GnRH agonist for the duration of protocol treatment
Women must be postmenopausal as defined as
-- Age 60 years or Age 45 with intact uterus and amenorrhea for 12 consecutive months or Follicle stimulating hormone FSH levels within postmenopausal range according to the ranges established by the testing facility or Premenopausal women who have been on a GnRH agonist for at least 6 weeks prior to study entry Women in this group MUST remain on the GnRH agonist for the duration of protocol treatment or Status post bilateral oophorectomy after adequate healing post-surgery
Prior hormonal therapy
Participants may have received any number of previous endocrinehormonal lines of therapy in the metastatic setting as long as the last dose is 14 days prior to registration
No prior fulvestrant
Participants may have received up to one prior line of chemotherapy for advanced breast cancer as long as the last dose is 21 days prior to registration
Prior therapy with biologics and investigational drugs is allowed as long as the last dose is 21 days prior to registration
No prior CDK46 inhibitors
No prior PD1PDL1CTLA4 inhibitors
Participants may have received radiotherapy for palliative purposes but must have completed treatment 14 days prior to registration and not be experiencing grade 1 treatment-related toxicities
Measurable disease by RECIST 11
Participants with accessible tumor lesions must be willing to undergo two research biopsies one prior to treatment initiation and one after 7 weeks of protocol therapy Participants who undergo an attempted on-treatment research biopsy and in whom inadequate tissue is obtained are still eligible to receive protocol therapy They will not be required to undergo a repeat research biopsy attempt If a biopsy-accessible participant has had a biopsy within 30 days of treatment initiation for clinical purposes they may choose to submit an archived specimen from this procedure instead
The FDA the US Food and Drug Administration has approved LEE011 as a treatment for hormone receptor positive metastatic breast cancer
The FDA has not approved PDR001 as treatment for any type of cancer
The FDA has approved fulvestrant as a treatment for hormone receptor positive metastatic breast cancer
When given separately these medications work in different ways to try and stop cancer cells from growing and spreading
LEE011 is a drug designed to block certain proteins called cyclin-dependent kinases CDKs that are required for cells to divide These proteins may also control the ability of certain cancers to grow
PDR001 is an antibody Antibodies are proteins usually produced by the body that help protect against foreign matter such as bacteria and viruses PDR001 blocks a protein called PD-1 which is present on cells called T-lymphocytes which are involved in the immune response PDR001 is being tested to see if it will allow the bodys immune system to work against tumor cells Other studies have shown that blocking PD-1 may result in reduced tumor cell growth in a variety of solid tumors
Fulvestrant is an estrogen receptor antagonist that is indicated for the treatment of postmenopausal women with HR MBC
In this research study the investigators are looking for a safe and tolerable dose of LEE011 that can be given in combination with PDR001 for participants with metastatic hormone-receptor-positive HR HER2-negative breast cancer in combination with fulvestrant or metastatic epithelial ovarian cancer
ELIGIBILITY FOR COHORT A DOSE ESCALATION Ribociclib PDR001
Hormone receptor HR-positive HER2-negative metastatic breast cancer according to ASCO CAP Guidelines
Participants may have received any number of previous endocrinehormonal lines of therapy in the metastatic setting as long as the last dose is 14 days prior to registration
Participants may have received any number of prior lines of chemotherapy for advanced breast cancer as long as the last dose is 21 days prior to registration
Prior therapy with biologics and investigational drugs is allowed as long as the last dose is 21 days prior to registration
Prior CDK46 inhibition is allowed Participants who have had prior ribociclib must have received treatment at full-dose without any dose-reductions The last dose is required to be 21 days prior to registration
No prior PD1PDL1CTLA4 inhibitors
Participants may have received radiotherapy for palliative purposes but must have completed treatment 14 days prior to registration and not be experiencing grade 1 treatment related toxicities
Men are eligible as long as on a GnRH agonist for at least 6 weeks prior to study entry Men MUST remain on the GnRH agonist for the duration of protocol treatment
Evaluable or measurable disease by RECIST 11
Metastatic epithelial ovarian cancer fallopian tube or peritoneal cancer All histologies including serous mucinous endometrioid clear cell MMMTs and mix histologies and tumor grades are eligible
Must have received a first-line platinum-based therapy and have disease that is platinum-resistant
--- Platinum-resistant disease is defined as disease relapse within 2 to 6 months of prior platinum-based chemotherapy
There is no limit to the number of lines of prior chemotherapy biology or hormonal therapy regimens
No prior PD1PDL1CTLA4 inhibitors
Evaluable or measurable disease by RECIST 11
ELIGIBILITY FOR COHORT A DOSE EXPANSION Ribociclib PDR001
Metastatic epithelial ovarian cancer fallopian tube or peritoneal cancer All histologies including serous mucinous endometrioid clear cell MMMTs and mixed histologies and tumor grades are eligible
Must have received a first-line platinum-based chemotherapy regimen and have relapsed despite standard therapy
Must have received a first-line platinum-based therapy and have disease that is platinum-resistant
--- Platinum-resistant disease is defined as disease relapse within 2 to 6 months of prior platinum-based chemotherapy
There is no limit to the number of lines of prior chemotherapy biology or hormonal therapy regimens
Patients may have received any number of previous endocrine hormonal lines of therapy in the metastatic setting as long as the last dose is 14 days prior to first dose of study treatment
Prior therapy with biologics and investigational drugs is allowed as long as the last dose is 21 days prior to first dose of study treatment
No prior CDK46 inhibitors
No prior PD1PDL1CTLA4 inhibitors
Measurable disease by RECIST 11
Participants with accessible tumor lesions must be willing to undergo two research biopsies one prior to treatment initiation and one after 7 weeks of protocol therapy Participants who undergo an attempted on-treatment research biopsy and in whom inadequate tissue is obtained are still eligible to receive protocol therapy They will not be required to undergo a repeat research biopsy attempt If a biopsy-accessible participant has had a biopsy within 30 days of treatment initiation for clinical purposes they may choose to submit an archived specimen from this procedure instead
ELIGIBILITY FOR COHORT B SAFETY RUN-IN Ribociclib PDR001 Fulvestrant
Hormone receptor HR-positive HER2-negative metastatic breast cancer according to ASCO CAP Guidelines
Men are eligible as long as on a GnRH agonist for at least 6 weeks prior to study entry Men MUST remain on the GnRH agonist for the duration of protocol treatment
Women must be postmenopausal as defined as
-- Age 60 years or Age 45 with intact uterus and amenorrhea for 12 consecutive months or Follicle stimulating hormone FSH levels within postmenopausal range according to the ranges established by the testing facility or Premenopausal women who have been on a GnRH agonist for at least 6 weeks prior to study entry Women in this group MUST remain on the GnRH agonist for the duration of protocol treatment or Status post bilateral oophorectomy after adequate healing post-surgery
Evaluable or measurable disease by RECIST 11
Prior CDK46 inhibition is allowed Participants who have had prior ribociclib must have received treatment at full-dose without any dose-reductions The last dose is required to be 21 days prior to registration
Prior hormonal therapy
Prior therapy with Fulvestrant is allowed
Participants may have received any number of previous endocrinehormonal lines of therapy in the metastatic setting as long as the last dose is 14 days prior to registration
Participants may have received chemotherapy for advanced breast cancer as long as the last dose is 21 days prior to registration
Prior therapy with biologics and investigational drugs is allowed as long as the last dose is 21 days prior to registration
Participants may have received radiotherapy for palliative purposes but must have completed treatment 14 days prior to registration and not be experiencing grade 1 treatment related toxicities
ELIGIBILITY FOR COHORT B DOSE EXPANSION Ribociclib PDR001 Fulvestrant
Hormone receptor HR-positive HER2-negative metastatic breast cancer according to ASCO CAP Guidelines
Men are eligible as long as on a GnRH agonist for at least 6 weeks prior to study entry Men MUST remain on the GnRH agonist for the duration of protocol treatment
Women must be postmenopausal as defined as
-- Age 60 years or Age 45 with intact uterus and amenorrhea for 12 consecutive months or Follicle stimulating hormone FSH levels within postmenopausal range according to the ranges established by the testing facility or Premenopausal women who have been on a GnRH agonist for at least 6 weeks prior to study entry Women in this group MUST remain on the GnRH agonist for the duration of protocol treatment or Status post bilateral oophorectomy after adequate healing post-surgery
Prior hormonal therapy
Participants may have received any number of previous endocrinehormonal lines of therapy in the metastatic setting as long as the last dose is 14 days prior to registration
No prior fulvestrant
Participants may have received up to one prior line of chemotherapy for advanced breast cancer as long as the last dose is 21 days prior to registration
Prior therapy with biologics and investigational drugs is allowed as long as the last dose is 21 days prior to registration
No prior CDK46 inhibitors
No prior PD1PDL1CTLA4 inhibitors
Participants may have received radiotherapy for palliative purposes but must have completed treatment 14 days prior to registration and not be experiencing grade 1 treatment-related toxicities
Measurable disease by RECIST 11
Participants with accessible tumor lesions must be willing to undergo two research biopsies one prior to treatment initiation and one after 7 weeks of protocol therapy Participants who undergo an attempted on-treatment research biopsy and in whom inadequate tissue is obtained are still eligible to receive protocol therapy They will not be required to undergo a repeat research biopsy attempt If a biopsy-accessible participant has had a biopsy within 30 days of treatment initiation for clinical purposes they may choose to submit an archived specimen from this procedure instead
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?:
None
Is an FDA AA801 Violation?:
None