September 19, 2017
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September 27, 2017
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March 31, 2022
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November 8, 2017
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October 14, 2020 (Final data collection date for primary outcome measure)
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- Cohort A: MTD/RP2D of the Combination of Ribociclib + PDR001 [ Time Frame: 4 weeks ]
Toxicity will be graded according to NCI CTCAE, Version 4.0.
- Cohort B: MTD/RP2D of the Combination of Ribociclib + PDR001 + Fulvestrant [ Time Frame: 4 weeks ]
Toxicity will be graded according to NCI CTCAE, Version 4.0.
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Same as current
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- Number of Participants with Adverse Events [ Time Frame: All participants will be evaluable for toxicity from the time of their first treatment with any study agent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months ]
Toxicity will be graded according to NCI CTCAE, Version 4.0.
- Objective Response Rate [ Time Frame: 2 Years ]
ORR is defined as the proportion of patients with complete response or partial response by RECIST 1.1 and immune-related RECIST (irRECIST)
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Same as current
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Not Provided
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Not Provided
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Ribociclib + PDR001 in Breast Cancer and Ovarian Cancer
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A Phase 1 Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Combination With the PD-1 Inhibitor PDR001 in Patients With Metastatic Hormone Receptor-positive Breast Cancer and Metastatic Ovarian Cancer
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This clinical trial is studying the drug Ribociclib (LEE011) in combination with an immunotherapy drug called PDR001 (a therapy that uses the body's 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
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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 endocrine/hormonal 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 CDK4/6 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 PD1/PDL1/CTLA4 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 1.1.
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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
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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 PD1/PDL1/CTLA4 inhibitors
- Evaluable or measurable disease by RECIST 1.1.
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.
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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.
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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 CDK4/6 inhibitors.
- No prior PD1/PDL1/CTLA4 inhibitors.
- Measurable disease by RECIST 1.1.
- Participants with accessible tumor lesion(s) 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 1.1.
- Prior CDK4/6 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 endocrine/hormonal 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
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Prior hormonal therapy:
- Participants 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 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 CDK4/6 inhibitors
- No prior PD1/PDL1/CTLA4 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 1.1.
- Participants with accessible tumor lesion(s) 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.
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Interventional
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Phase 1
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Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
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- Metastatic Hormone-Receptor-Positive (HR+) Breast Cancer
- HER2-Negative Breast Cancer
- Metastatic Epithelial Ovarian Cancer
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- Drug: Ribociclib
Each treatment cycle lasts 28 days. Ribociclib, 1 time per day by mouth for 21 days, followed by 1-week of rest (28-day cycle)
- Drug: PDR001
Each treatment cycle lasts 28 days. (PDR001) will be administered once every 28 days (by intravenous infusion) over about 30 minutes (or up to 2 hours, if necessary) for the first infusion and over about 30 minutes for all following infusions.
- Drug: Fulvestrant
Each treatment cycle lasts 28 days. Fulvestrant will be administered during Cycle 1 on days 1 and 15, and then on day 1 of each 28-day cycle thereafter.
Other Names:
- Faslodex
- ICI 182,780
- ZD9238
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- Experimental: Ribociclib and PDR001 (Cohort A)
Interventions:
- Drug: Ribociclib
- Drug: PDR001
- Experimental: Ribociclib, PDR001 and Fulvestrant (Cohort B)
Interventions:
- Drug: Ribociclib
- Drug: PDR001
- Drug: Fulvestrant
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Not Provided
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Terminated
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33
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60
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October 14, 2020
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October 14, 2020 (Final data collection date for primary outcome measure)
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Inclusion Criteria
Note: Highly effective contraception methods include:
Exclusion Criteria:
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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United States
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|
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NCT03294694
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17-285
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Sara Tolaney, Dana-Farber Cancer Institute
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Christina I Herold, MD, Dana-Farber Cancer Institute, Principal Investigator
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Dana-Farber Cancer Institute
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Same as current
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Novartis
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Principal Investigator: |
Sara Tolaney, MD |
Dana-Farber Cancer Institute |
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Dana-Farber Cancer Institute
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March 2022
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