Breast CancerPhase 1/2NCT02379247
BYL719 and Nab-Paclitaxel in Locally Recurrent or Metastatic HER-2 Negative Breast Cancer
A Phase 1/2 study testing BYL-719 (alpelisib) and Nab-paclitaxel in people with Breast Cancer, run by Priyanka Sharma at 4 sites in United States.
Trial summary
Investigate the use of BYL719 (alpelisib) as combination therapy with Nab-Paclitaxel in locally recurrent or metastatic HER-2 negative breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- BYL-719 (alpelisib) and Nab-paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 4 sitesUnited States
- Study dates
- Feb 2015to Mar 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- AST(SGOT)/ALT(SPGT) ≤ 2.5X IULN or ≤ 5X IULN if liver metastases are present
- Serum creatinine ≤ 1.5X IULN
- INR ≤ 1.5
- Fasting plasma glucose ≤ 140 mg/dL or 7.8 mmol/L (NOTE: Fasting whole blood glucose testing is acceptable if fasting plasma glucose is not feasible.)
- HBA1c ≤ 8%
- Potassium, calcium (corrected for serum albumin) and magnesium within IULN
- Serum Amylase < 2 x ULN and serum lipase within normal limits
- IV bisphosphate and denosumab for bony metastatic disease will be allowed
- Prior palliative radiation therapy to bony metastases is allowed. There should be a minimum of 14 days between the end of radiation treatment and start of study treatment
- Subjects with previously treated brain metastases who are free of CNS symptoms and are > 3 months from treatment of brain metastases are eligible Subjects should be > 2 weeks from prior systemic chemotherapy for breast cancer AND should have recovered to Grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy prior to study entry 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.
- Women of child bearing potential (WOCBP) and their partners must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. After confirmation of negative pregnancy test at screening, should a WOCBP become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician and the investigator immediately.
- WOCBP are defined as any females (regardless of sexual orientation, having undergone tubal ligation, or remaining celibate by choice) who meet the following criteria:
- Have not undergone a hysterectomy or bilateral oophorectomy OR
- Have not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months)
Who cannot join
- 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)
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- 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
- Symptomatic peritonitis
- Documented myocardial infarction within 6 months prior to study entry
- History of documented congestive heart failure (New York Heart Association functional classification III-IV)
- Documented cardiomyopathy
- Subject has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated Acquisition (MUGA) scan or echocardiogram (ECHO)
- Subject has any of the following cardiac conduction abnormalities
- Ventricular arrhythmias except for benign premature ventricular contractions
- Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medicine
- Conduction abnormality requiring a pacemaker
- Other cardiac arrhythmia not controlled with medication
- Subject has a QTcF > 480 msec on the screening ECG (using the QTcF formula)
- Subject is currently receiving treatment with a medication that has a known risk to prolong the QT interval or induce Torsades de Pointes and the treatment cannot be discontinued or switched to a different medication prior to randomization
- Subject has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects
- Subject is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug or who have not fully recovered from side effects of such treatment
- Subject is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The subject must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the start of treatment
- Subject is currently receiving warfarin or other coumarin-derived anti-coagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed
- Subject has received previous treatment with a PI3K inhibitor. Exceptions may be made for subjects who discontinued treatment with a previous PI3K inhibitor for reasons other than toxicity or progression and as long as it has been > 12 months since discontinuation of the previous PI3K inhibitor. This exception will require prior approval from the study PI at KUMC.
- Subjects who have received an investigational agent within 30 days OR within 5 half-lives of the investigational agent (whichever is shorter) prior to the possible enrollment date on this study.
- Subject with history of acute within one year of study entry or past medical history of chronic pancreatitis.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Kansas Cancer Center
Kansas City, Kansas, 66205
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
University of Kansas Cancer Center - Overland Park
Overland Park, Kansas, 66210
About this study
Official title: Phase I/II Study of BYL719 and Nab-Paclitaxel in Subjects With Locally Recurrent or Metastatic HER-2 Negative Breast Cancer
Investigate the use of BYL719 (alpelisib) as combination therapy with Nab-Paclitaxel in locally recurrent or metastatic HER-2 negative breast cancer.
Read the detailed description
Breast cancer is the most common cancer and the second leading cause of cancer related death in American women. Despite recent improvement in the treatment of breast cancer, 40,000 women still die each year in the US as a result of breast cancer. Chemotherapy (usually consisting of sequential single agent) remains the backbone of treatment for patients with HER-2 negative metastatic breast cancer. A majority of patients show an initial response to treatment, but all eventually show disease progression.
The purpose of this study is to determine the highest dose of BYL719 (alpelisib) combined with Nab-Paclitaxel that results in no serious side effects. The safety and effectiveness of BYL719 combined with Nab-Paclitaxel to treat patients with HER-2 negative metastatic breast cancer will be assessed, along with the determination of how long this drug combination will keep the disease from getting worse.
The study will be done in two parts:
Part 1 will determine the highest dose of BYL719 that is safe and tolerable to take in combination with Nab-Paclitaxel. Part 1 will be completed before Part 2 begins.
Part 2 will investigate whether taking BYL719 (at the dose determined in Part 1) + Nab-Paclitaxel is safe and effective for patients with HER-2 negative metastatic breast cancer.
- Conditions
- Breast Cancer
- Being tested
- BYL-719 (alpelisib), Nab-paclitaxel
- Keywords
- HER-2 Negative, Metastatic Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BYL-719 (alpelisib)Drug
Also called Piqray
Oral PI3K inhibitor
Nab-paclitaxelDrug
Also called Abraxane
IV taxane
| Study group | Role | What they receive |
|---|---|---|
| Dose level 1 BYL-719/alpelisib (250mg)+Nab-paclitaxel | Experimental | BYL-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) Receives: Drug: BYL-719 (alpelisib); Drug: Nab-paclitaxel |
| Dose level 2 BYL-719 (alpelisib) (300mg)+Nab-paclitaxel | Experimental | BYL-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) Receives: Drug: BYL-719 (alpelisib); Drug: Nab-paclitaxel |
| Dose level 3 BYL-719 (alpelisib) (350mg)+Nab-paclitaxel | Experimental | BYL-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) Receives: Drug: BYL-719 (alpelisib); Drug: Nab-paclitaxel |
| BYL-719 (alpelisib) Dose Expansion | Experimental | BYL-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) Receives: Drug: BYL-719 (alpelisib); Drug: Nab-paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 24 months
Secondary outcomes (4)
Clinical Benefit Rate (CBR) at 16 Weeks of Study Treatment
CBR includes complete response (CR), partial response (PR), plus stable disease (SD) ≥16 weeks. As evaluated per RECIST version 1.1.
Measured: 16 weeks
Pharmacokinetics of BYL-719 (Alpelisib) When Administered With Nab-paclitaxel
Area under the curve (AUC): sampling pre-dose and 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-alpelisib dose
Measured: 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)
Area under the curve (AUC): sampling pre-dose and 1.5, 2, 2.5, 3, 3.5, 4, and 6 hours post-alpelisib dose
Measured: In cycle 1 day 1, from prior to alpelisib dosing through 8 hours after alpelisib dosing
Progression-free Survival (PFS) and Overall Survival (OS)
PFS was defined as the time in months from the date of enrollment to the date of progression or death, whichever was earlier. OS was defined as the time in months from the date of enrollment to death as a result of any cause. Survival curves were assessed by the Kaplan-Meier method.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2015 (estimated)
- Study startFeb 2015
- Primary completion21 Sep 2017
- Study completionMar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Priyanka Sharma
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor-investigator, Priyanka Sharma, University of Kansas Medical Center
- Investigators
- Priyanka Sharma, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02379247
- Sponsor's protocol ID
- CBYL719XUS06T
- Status last verified
- May 2022
- First submitted
- 30 Jan 2015
- Last updated
- 7 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 33602685
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of BYL719 and Nab-Paclitaxel in Subjects With Locally Recurrent or Metastatic HER-2 Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT02379247
- Acronym / sponsor ID
- CBYL719XUS06T
- Conditions
- Breast Cancer
- Keywords
- HER-2 Negative, Metastatic Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Priyanka SharmaUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- Feb 2015 (actual)
- Primary completion
- 21 Sep 2017 (actual)
- Study completion
- Mar 2022 (actual)
- First posted
- 4 Mar 2015 (estimated)
- Results
- Posted 28 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigate the use of BYL719 (alpelisib) as combination therapy with Nab-Paclitaxel in locally recurrent or metastatic HER-2 negative breast cancer.
Detailed description
Breast cancer is the most common cancer and the second leading cause of cancer related death in American women. Despite recent improvement in the treatment of breast cancer, 40,000 women still die each year in the US as a result of breast cancer. Chemotherapy (usually consisting of sequential single agent) remains the backbone of treatment for patients with HER-2 negative metastatic breast cancer. A majority of patients show an initial response to treatment, but all eventually show disease progression.
The purpose of this study is to determine the highest dose of BYL719 (alpelisib) combined with Nab-Paclitaxel that results in no serious side effects. The safety and effectiveness of BYL719 combined with Nab-Paclitaxel to treat patients with HER-2 negative metastatic breast cancer will be assessed, along with the determination of how long this drug combination will keep the disease from getting worse.
The study will be done in two parts:
Part 1 will determine the highest dose of BYL719 that is safe and tolerable to take in combination with Nab-Paclitaxel. Part 1 will be completed before Part 2 begins.
Part 2 will investigate whether taking BYL719 (at the dose determined in Part 1) + Nab-Paclitaxel is safe and effective for patients with HER-2 negative metastatic breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose level 1 BYL-719/alpelisib (250mg)+Nab-paclitaxel | Experimental | Drug: BYL-719 (alpelisib), Drug: Nab-paclitaxelBYL-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 | Experimental | Drug: BYL-719 (alpelisib), Drug: Nab-paclitaxelBYL-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 | Experimental | Drug: BYL-719 (alpelisib), Drug: Nab-paclitaxelBYL-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 | Experimental | Drug: BYL-719 (alpelisib), Drug: Nab-paclitaxelBYL-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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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
Key exclusion criteria (34 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BYL-719 (alpelisib)Also: PiqrayOral PI3K inhibitor | Drug | BYL-719 (alpelisib) Dose Expansion, Dose level 1 BYL-719/alpelisib (250mg)+Nab-paclitaxel, Dose level 2 BYL-719 (alpelisib) (300mg)+Nab-paclitaxel, Dose level 3 BYL-719 (alpelisib) (350mg)+Nab-paclitaxel |
| Nab-paclitaxelAlso: AbraxaneIV taxane | Drug | BYL-719 (alpelisib) Dose Expansion, Dose level 1 BYL-719/alpelisib (250mg)+Nab-paclitaxel, Dose level 2 BYL-719 (alpelisib) (300mg)+Nab-paclitaxel, Dose level 3 BYL-719 (alpelisib) (350mg)+Nab-paclitaxel |
Primary outcome
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
Time frame: 12 months
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.
Phase II: Overall Response Rate (ORR) of Subjects Treated at the Recommended Phase II Dose (RP2D)
Time frame: 24 months
ORR includes complete response (CR) plus partial response (PR). As evaluated per RECIST version 1.1.
4 secondary outcomes
Clinical Benefit Rate (CBR) at 16 Weeks of Study Treatment
Time frame: 16 weeks
Pharmacokinetics of BYL-719 (Alpelisib) When Administered With Nab-paclitaxel
Time frame: 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)
Time frame: In cycle 1 day 1, from prior to alpelisib dosing through 8 hours after alpelisib dosing
Progression-free Survival (PFS) and Overall Survival (OS)
Time frame: 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 33602685Sharma 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Priyanka Sharma, MD principal investigator
University of Kansas Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BYL-719 (alpelisib) and Nab-paclitaxel in people with Breast Cancer, run by Priyanka Sharma at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02379247, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2022.