BYL719 and Nab-Paclitaxel in Locally Recurrent or Metastatic HER-2 Negative Breast Cancer
Phase I/II Study of BYL719 and Nab-Paclitaxel in Subjects With Locally Recurrent or Metastatic HER-2 Negative Breast Cancer
1 other identifier
interventional
43
1 country
4
Brief Summary
Investigate the use of BYL719 (alpelisib) as combination therapy with Nab-Paclitaxel in locally recurrent or metastatic HER-2 negative breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 breast-cancer
Started Feb 2015
Longer than P75 for phase_1 breast-cancer
4 active sites
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
January 30, 2015
CompletedStudy Start
First participant enrolled
February 1, 2015
CompletedFirst Posted
Study publicly available on registry
March 4, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 21, 2017
CompletedResults Posted
Study results publicly available
September 28, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2022
CompletedJune 7, 2022
May 1, 2022
2.6 years
January 30, 2015
May 7, 2021
May 16, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase I: Recommended Phase II Dose (RP2D) of BYL-719 (Alpelisib) + Nab-paclitaxel to be Used in Combination to Treat Advanced HER2-negative Breast Cancer
Phase I was a 3+3 dose escalation design (three dose levels of alpelisib: 250mg, 300mg, and 350mg orally once daily, continuous dosing) with dose-limiting toxicities (DLT) assessed during the first treatment cycle. If two or more of the six patients experienced a dose-limiting toxicity, dosing escalation would cease and maximum tolerated dose (MTD) would be reached. RP2D was the next lower dose at which \<1/6 subjects experienced a DLT.
12 months
Phase II: Overall Response Rate (ORR) of Subjects Treated at the Recommended Phase II Dose (RP2D)
ORR includes complete response (CR) plus partial response (PR). As evaluated per RECIST version 1.1.
24 months
Secondary Outcomes (4)
Clinical Benefit Rate (CBR) at 16 Weeks of Study Treatment
16 weeks
Pharmacokinetics of BYL-719 (Alpelisib) When Administered With Nab-paclitaxel
In cycle 1 day 1, from prior to alpelisib dosing through 8 hours after alpelisib dosing
Pharmacokinetics of (Total) Nab-paclitaxel When Administered With BYL-719 (Alpelisib)
In cycle 1 day 1, from prior to alpelisib dosing through 8 hours after alpelisib dosing
Progression-free Survival (PFS) and Overall Survival (OS)
36 months
Other Outcomes (1)
Correlation of PIK3CA Mutation With Clinical Benefit Rate
24 months
Study Arms (4)
Dose level 1 BYL-719/alpelisib (250mg)+Nab-paclitaxel
EXPERIMENTALBYL-719 (alpelisib): 250mg daily on day 1-28 Nab-paclitaxel: 100mg/m2 IV days 1, 8, 15 of each 28 day cycle (Window for Nab-paclitaxel is +/- 1 day)
Dose level 2 BYL-719 (alpelisib) (300mg)+Nab-paclitaxel
EXPERIMENTALBYL-719 (alpelisib): 300mg by mouth daily on day 1-28 of each 28 day cycle Nab-paclitaxel: 100mg/m2 given IV on days 1, 8, 15 of each 28 day cycle (Window for Nab-paclitaxel is +/- 1 day)
Dose level 3 BYL-719 (alpelisib) (350mg)+Nab-paclitaxel
EXPERIMENTALBYL-719 (alpelisib): 350mg by mouth daily on day 1-28 of each 28 day cycle Nab-paclitaxel: 100mg/m2 given IV on days 1, 8, 15 of each 28 day cycle (Window for Nab-paclitaxel is +/- 1 day)
BYL-719 (alpelisib) Dose Expansion
EXPERIMENTALBYL-719 (alpelisib): RP2D from Phase I by mouth daily on day 1-28 of each 28 day cycle Nab-paclitaxel: 100mg/m2 given IV on days 1, 8, 15 of each 28 day cycle (Window for Nab-paclitaxel is +/- 1 day)
Interventions
Oral PI3K inhibitor
IV taxane
Eligibility Criteria
You may qualify if:
- Ability to understand and the willingness to sign a written Informed Consent Form.
- Age ≥ 18 years
- Histologically proven HER-2 negative breast cancer (HER-2 negative defined as HER IHC 0 or 1+ and/or HER-2 FISH negative); HER-2 negative breast cancer includes hormone positive (ER and/or PR positive) breast cancer and TNBC
- HER-2 negative breast cancer that at the time of study entry is either stage III (locally advanced) disease not amenable to curative therapy or stage IV disease. Histological confirmation of recurrent/metastatic disease is encouraged but not required if clinical evidence of stage IV disease is available
- Have measurable (defined as at least one lesion that can be accurately measured in at least one dimension \[longest diameter to be recorded\] with minimum lesion size of ≥ 2 cm on conventional measurement techniques or ≥ 1 cm on spiral computed tomography (CT) scan
- No limitations to number of prior chemotherapies for metastatic disease. Treatment with prior taxanes (except Nab-Paclitaxel) is allowed as long as it has been 6 months or more since exposure to prior taxane.
- NOTE: For subjects who are, or who have previously received endocrine therapy for breast cancer, the treating investigator will decide how many days should pass between the last dose of endocrine therapy and the first dose of study treatment.
- All patients should have received at least one line of chemotherapy in either the advanced or adjuvant setting and hormonal therapy (where appropriate)
- Performance status of 2 or better as per ECOG criteria (See Appendix A for details)
- Subject is able to swallow and retain oral medicines
- Adequate marrow and organ function as defined below (labs must be performed within 14 days of subject registration)
- Absolute neutrophil count ≥ 1500/uL
- Platelets 100,000/uL (no transfusion allowed within 2 weeks)
- Hemoglobin \> 9 g/dL (which may be reached by transfusion)
- Total bilirubin within normal range or ≤ 1.5X IULN if liver metastases are present or total bilirubin ≤ 3.0X IULN with direct bilirubin within normal range in subjects with well-documented Gilbert's Syndrome, which is defined as presence of unconjugated hyperbilirubinemia with normal results from CBC (including normal reticulocyte count and blood smear), normal liver function test results and absence of other contributing disease processes at the time of diagnosis
- +14 more criteria
You may not qualify if:
- Subject has any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of drugs in this protocol or place the subject at undue risk for treatment complications
- Subject is pregnant or lactating
- Subject has previously been treated with Nab-Paclitaxel NOTE: Subjects who have had previous treatment with Nab-Paclitaxel will NOT be excluded if given in the adjuvant or neoadjuvant setting Only in the metastatic setting, will subjects previously treated with Nab-Paclitaxel be excluded from this trial. Exceptions may be made for subjects who discontinued treatment with a previous Nab-Paclitaxel inhibitor for reasons other than progression and as long as it has been \> 12 months since discontinuation of the previous Nab-Paclitaxel. This exception will require prior approval from the study PI at KUMC.
- Subject has inflammatory breast cancer
- Subject has a known hypersensitivity to any of the excipients of Nab-Paclitaxel or BYL719/alpelisib
- Subject has a concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer)
- Subject has clinically manifest diabetes mellitus or documented steroid-induced diabetes mellitus
- Subject has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Subject is classified into Child-Pugh class C
- Subject has a known history of HIV infection (testing not mandatory)
- Subject has active, uncontrolled infection
- Subject has symptomatic/untreated CNS disease
- Subject has ≥ Grade 2 peripheral neuropathy
- Subject has active cardiac disease or a history of cardiac dysfunction including any of the following:
- Unstable angina pectoris within 6 months prior to study entry
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Priyanka Sharmalead
- Novartis Pharmaceuticalscollaborator
Study Sites (4)
University of Kansas Cancer Center
Kansas City, Kansas, 66205, United States
University of Kansas Cancer Center - Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Related Publications (1)
Sharma P, Abramson VG, O'Dea A, Nye L, Mayer I, Pathak HB, Hoffmann M, Stecklein SR, Elia M, Lewis S, Scott J, De Jong JA, Wang YY, Yoder R, Schwensen K, Finke K, Heldstab J, LaFaver S, Williamson SK, Phadnis MA, Reed GA, Kimler BF, Khan QJ, Godwin AK. Clinical and Biomarker Results from Phase I/II Study of PI3K Inhibitor Alpelisib plus Nab-paclitaxel in HER2-Negative Metastatic Breast Cancer. Clin Cancer Res. 2021 Jul 15;27(14):3896-3904. doi: 10.1158/1078-0432.CCR-20-4879. Epub 2021 Feb 18.
PMID: 33602685RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Priyanka Sharma
- Organization
- University of Kansas Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Priyanka Sharma, MD
University of Kansas Medical Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Medical Doctor
Study Record Dates
First Submitted
January 30, 2015
First Posted
March 4, 2015
Study Start
February 1, 2015
Primary Completion
September 21, 2017
Study Completion
March 1, 2022
Last Updated
June 7, 2022
Results First Posted
September 28, 2021
Record last verified: 2022-05