Study Stopped
Insufficient accrual
Copanlisib, Letrozole, and Palbociclib in Treating Patients With Hormone Receptor Positive HER2 Negative Stage I-IV Breast Cancer
A Phase Ib Trial Evaluating the Safety of Copanlisib, Letrozole, and Palbociclib in Metastatic Breast Cancer and Phase II Trial Comparing the Molecular Effects of Neoadjuvant Copanlisib in Combination With Palbociclib and Letrozole, vs. Copanlisib With Letrozole, vs. Palbociclib With Letrozole for Patients With Hormone Receptor Positive, HER2 Normal Breast Cancer
2 other identifiers
interventional
10
1 country
1
Brief Summary
This phase I/II trial studies side effects and best dose of copanlisib when given together with letrozole and palbociclib and to see how well they work in treating hormone receptor positive HER2 negative stage I-IV breast cancer. Copanlisib and palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs, such as letrozole, may lessen the amount of estrogen made by the body. Giving copanlisib, letrozole, and palbociclib may work better in treating patients with breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Aug 2017
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 4, 2017
CompletedFirst Posted
Study publicly available on registry
April 25, 2017
CompletedStudy Start
First participant enrolled
August 2, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2022
CompletedSeptember 26, 2022
April 1, 2021
4.7 years
April 4, 2017
September 22, 2022
Conditions
Outcome Measures
Primary Outcomes (2)
Change in Ki-67 expression defined as the percent of cells staining positive by validated central assay (Phase II)
Will be evaluated on the log Ki-67 ratio scale. Primary analysis of this variable will utilize a linear model with treatment, PR status as fixed effects. The comparison of treatment arms will be based on the least squares mean (LSM) estimates and standard errors derived from this model. For descriptive purposes, LSM estimates and associated confidence intervals (CIs) will be back transformed to the geometric mean percent change scale. A second post-baseline evaluation of Ki67 expression will be performed following the completion of 4 months of treatment. Analysis of change from baseline to com
Baseline to 2 weeks
Incidence of dose-limiting toxicities (DLT) evaluated according to National Cancer Institute (NCI) CTCAE version 4.0 to determine MTD (Phase Ib)
If \>= 2 of 6 participants treated at a dose level experience DLTs, then the MTD will have been exceeded. Up to 3 additional patients may be entered at the lower dose level to obtain additional safety information (if only 3 participants were treated previously at that dose) to demonstrate that =\< 1 of 6 patients experience DLT.
Up to 112 days
Secondary Outcomes (10)
Clinical objective response rate (ORR) evaluated by RECIST 1.1 using caliper measurements
Up to 1 month after surgery
Gene expression and/or biomarker changes
Up to 1 month after surgery
Incidence of adverse events (AEs) evaluated according to NCI CTCAE version 4.0
Up to 1 month after surgery
pCR rate defined as the percentage of randomized patients with a pCR
Up to 1 month after surgery
The pharmacokinetic (PK) parameter - area under the plasma concentration-time curve (AUC) will be determined for copanlisib in arms A, B, and escalation dose levels.
At pre-infusion, 10 minutes, 1, 2, 3, and 5 hours after start of infusion on days 1 and 8, course 1 (Ib); at pre-infusion and 1 hour after start of infusion on day 1, course 1 and pre-infusion, 5-15 minutes, 1, and 1-1.5 hours on day 8, course 2 (II)
- +5 more secondary outcomes
Study Arms (4)
Arm A (copanlisib, letrozole)
EXPERIMENTALPHASE II: Patients receive copanlisib (MTD) IV over 1 hour on days 1, 8, and 15 and letrozole PO continuously on days 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression, or unacceptable toxicity.
Arm B (copanlisib, palbociclib, letrozole)
EXPERIMENTALPHASE II: Patients receive copanlisib (MTD) IV over 1 hour on days 1, 8, and 15, palbociclib PO QD on days 1-21, and letrozole PO continuously on days 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Arm C (copanlisib, palbociclib, letrozole)
EXPERIMENTALPHASE II: Patients receive palbociclib PO QD for days 1-14 of course 1 and letrozole PO continuously on days 1-14. Patients then undergo biopsy. Patients then receive copanlisib IV over 1 hour on days 1, 8, and 15 and letrozole PO continuously on days 1-28. Treatment with copanlisib (MTD) and letrozole repeats every 28 days for up to 3.5 courses in the absence of disease progression or unacceptable toxicity.
Phase Ib (copanlisib, palbociclib, letrozole)
EXPERIMENTALPHASE Ib: Patients with metastatic breast cancer receive copanlisib IV over 1 hour on days 1, 8, and 15, palbociclib PO QD on days 1-21, and letrozole PO continuously on days 1-28. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Undergo biopsy
Given IV
Correlative studies
Given PO
Given PO
Correlative studies
Eligibility Criteria
You may qualify if:
- Post-menopausal (if female) defined as: 1) prior bilateral oophorectomy, 2) age 60 or over, or 3) \< 60 years and amenorrheic for at least 12 months with follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range per institutional parameters); use of luteinizing hormone-releasing hormone (LHRH) agonists to induce chemical ovarian ablation will not be allowed for this study
- Tumor is hormone receptor (HR)+ (estrogen receptor and/or progesterone receptor positive with at least 10% expression of either receptor by local immunohistochemical staining) and HER2 negative based on local assessment
- FOR PHASE Ib PORTION OF THE STUDY:
- Locally advanced/non-operable or metastatic breast cancer that has not been previously treated in the metastatic setting with systemic therapy (i.e. first line treatment)
- Measurable disease per RECIST 1.1
- FOR PHASE II PORTION OF THE STUDY:
- Breast cancer suitable for mandatory baseline core biopsy
- No prior systemic therapy or radiotherapy for currently-diagnosed invasive or noninvasive breast cancer
- FOR ALL PHASES (Ib AND II):
- Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
- Platelets \> 100 x 10\^9/L
- Hemoglobin \>= 8 g/dL (phase Ib) or \>= 10 g/dL (for phase II portion)
- For phase Ib portion only: patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; however, initial study drug treatment must not begin earlier than the day of the erythrocyte transfusion
- Bilirubin =\< 1.5 times the upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3.0 times ULN
- +6 more criteria
You may not qualify if:
- FOR PHASE Ib ONLY:
- Early stage (curable) breast cancer
- FOR PHASE II ONLY:
- Metastatic breast cancer (local spread to axillary or internal mammary lymph nodes is permitted)
- Prior systemic therapy for invasive or non-invasive (DCIS) breast cancer
- Prior radiotherapy to the ipsilateral chest wall or breast for any malignancy
- Bilateral invasive breast cancer
- FOR ALL PHASES (Ib AND II): Inflammatory breast cancer
- FOR ALL PHASES (Ib AND II): Concurrent therapy with any other non-protocol anti-cancer therapy
- FOR ALL PHASES (Ib AND II): History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix
- FOR ALL PHASES (Ib AND II): Concurrent diagnosis of pheochromocytoma
- FOR ALL PHASES (Ib AND II): Current therapy with raloxifene, tamoxifen, aromatase inhibitor, or other selective estrogen receptor modulator (SERM), either for osteoporosis or prevention of breast cancer; subjects must have discontinued therapies for at least 28 days prior to first baseline biopsy
- FOR ALL PHASES (Ib AND II): Concurrent treatment with postmenopausal hormone replacement therapy; prior treatment must be stopped for at least 28 days prior to first baseline biopsy
- FOR ALL PHASES (Ib AND II): Type I diabetes or patients on insulin therapy are not allowed; uncontrolled type II diabetes not allowed (glycosylated hemoglobin \[HbA1c\] \> 7.5)
- FOR ALL PHASES (Ib AND II): Proteinuria of \>= Common Terminology Criteria for Adverse Events (CTCAE) grade 3 as estimated by urine protein : creatinine ratio \> 3.5 on a random urine sample
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Jonsson Comprehensive Cancer Centerlead
- Bayercollaborator
- Translational Research in Oncology-U.S. Inc. (TRIO-US)collaborator
Study Sites (1)
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sara Hurvitz
UCLA / Jonsson Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 4, 2017
First Posted
April 25, 2017
Study Start
August 2, 2017
Primary Completion
March 31, 2022
Study Completion
March 31, 2022
Last Updated
September 26, 2022
Record last verified: 2021-04