Breast CancerPhase 2NCT01923168
Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women
A Phase 2 study testing alpelisib and buparlisib in people with Breast Cancer, run by Novartis Pharmaceuticals at 86 sites in 17 countries.
Trial summary
The purpose of the study was to determine whether treatment with a PI3K inhibitor plus letrozole led to an increase in pathologic clinical response and Objective Response Rate compared to treatment with placebo plus letrozole in patients with Breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- alpelisib and buparlisib
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 340 participants
- Where
- 86 sitesin 17 countries
- Study dates
- 11 Mar 2014to 8 Jul 2017
- Phase
- Phase 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is an adult, female ≥ 18 years old at the time of informed consent
- Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer
- Patient is postmenopausal.
- Patient has T1c-T3, any N, M0, operable breast cancer
- Patients must have measurable disease
- Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67 level.
- Patient has estrogen-receptor and/or progesterone positive breast cancer as per local laboratory testing
- Patient has HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0 or 1+ as per local laboratory testing
Who cannot join
- Patient has locally recurrent or metastatic disease
- Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease before randomization.
- Patient with type 1 diabetes mellitus or not adequately controlled type 2 diabetes mellitus
- History of acute pancreatitis within 1 year of study entry
- Uncontrolled hypertension
Trial locations and contacts
86 sites in 17 countries.
86 sites in 17 countries
United States23 sites
Emory University School of Medicine/Winship Cancer Institute SC
Atlanta, Georgia, 30322
Mercy Medical Center Medical Oncology & Hematology
Baltimore, Maryland, 21202
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Johns Hopkins Med. BYL719A2201
Baltimore, Maryland, 21231
Texas Oncology, P.A.
Bedford, Texas, 76022
University of Alabama at Birmingham/ Kirklin Clinic Univ AL - PI
Birmingham, Alabama, 35294-0006
Dana Farber Cancer Institute BYL719A2201
Boston, Massachusetts, 02215
Presbyterian Hospital of Dallas TexasOncology@PresbyterianHosp
Dallas, Texas, 75231
Texas Oncology Texas Oncology - Sammons
Dallas, Texas, 75246
Duke University Medical Center Duke University Medical Center
Durham, North Carolina, 27710
Highlands Oncology Group
Fayetteville, Arkansas, 72703
Texas Oncology Houston Memorial City SC
Houston, Texas, 77024
Los Angeles Hematology/Oncology Medical Group Onc Dept.
Los Angeles, California, 90017
University of California at Los Angeles UCLA SC
Los Angeles, California, 90095
Vanderbilt Ingram Cancer Center Vanderbilt Health 100 Oaks
Nashville, Tennessee, 37203
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Virginia Oncology Associates SC
Norfolk, Virginia, 23502
Northwest Cancer Specialists Vancouver Loc
Portland, Oregon, 97210
Mayo Clinic - Rochester BYL719A2201 - SC
Rochester, Minnesota, 55905
Cancer Care Centers of South Texas HOAST CCC of So. TX- San Antonio(2)
San Antonio, Texas, 78229
Cancer Therapy & Research Center UT Health Science Center InstituteForDrugDevelopment(5)
San Antonio, Texas, 78229
University of California San Francisco BYL719A2201 - SC
San Francisco, California, 94115
Seattle Cancer Care Alliance SC-3
Seattle, Washington, 98105
Northwest Medical Specialties Dept.ofNW Med. Specialties
Tacoma, Washington, 98405
Spain9 sites
Novartis Investigative Site
A Coruña, Galicia, 15006
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Donostia / San Sebastian, Basque Country, 20014
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Madrid, 28007
Novartis Investigative Site
Madrid, 28040
Novartis Investigative Site
Madrid, 28050
Novartis Investigative Site
Seville, Andalusia, 41017
Novartis Investigative Site
Valencia, Valencia, 46010
Austria7 sites
Novartis Investigative Site
Dornbirn, Vorarlberg, 6830
Novartis Investigative Site
Innsbruck, Tyrol, 6020
Novartis Investigative Site
Leoben, A-8700
Novartis Investigative Site
Rankweil, A-6830
Novartis Investigative Site
Salzburg, 5020
Novartis Investigative Site
Vienna, A-1090
Novartis Investigative Site
Villach, 9500
Japan6 sites
Novartis Investigative Site
Bunkyo-ku, Tokyo, 113-8677
Novartis Investigative Site
Hiroshima, Hiroshima, 730-8518
Novartis Investigative Site
Koto-ku, Tokyo, 135 8550
Novartis Investigative Site
Nagoya, Aichi-ken, 467-8602
Novartis Investigative Site
Niigata, 951-8566
Novartis Investigative Site
Osaka, Osaka, 540-0006
Brazil5 sites
Novartis Investigative Site
Goiânia, Goiás, 74605-070
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90610-000
Novartis Investigative Site
Ribeirão Preto, São Paulo, 14048-900
Novartis Investigative Site
São Paulo, São Paulo, 01317-002
Novartis Investigative Site
São Paulo, São Paulo, 03102-002
Germany5 sites
Novartis Investigative Site
Berlin, 13125
Novartis Investigative Site
Cologne, 51067
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
Essen, 45136
Novartis Investigative Site
Kiel, 24105
Italy5 sites
Novartis Investigative Site
Brescia, BS, 25127
Novartis Investigative Site
Cremona, CR, 26100
Novartis Investigative Site
Milan, MI, 20141
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Province of Macerata, MC, 62100
Canada4 sites
Novartis Investigative Site
Montreal, Quebec, H2W 1T8
Novartis Investigative Site
Montreal, Quebec, H3T 1E2
Novartis Investigative Site
Québec, Quebec, G1S 4L8
Novartis Investigative Site
Vancouver, British Columbia, V5Z 4E6
Netherlands4 sites
Novartis Investigative Site
Delft, 2625 AD
Novartis Investigative Site
Leiden, 2300 RC
Novartis Investigative Site
The Hague, 2545 CH
Novartis Investigative Site
Tilburg, 5022 GC
Belgium3 sites
Novartis Investigative Site
Edegem, Antwerpen, 2650
Novartis Investigative Site
Leuven, 3000
Novartis Investigative Site
Sint-Niklaas, 9100
Bulgaria3 sites
Novartis Investigative Site
Shumen, 9700
Novartis Investigative Site
Sofia, 1303
Novartis Investigative Site
Varna, 9010
Israel3 sites
Novartis Investigative Site
Haifa, 3525408
Novartis Investigative Site
Ramat Gan, 5265601
Novartis Investigative Site
Tel Aviv, 64239
Lebanon3 sites
Novartis Investigative Site
Beirut
Novartis Investigative Site
El Achrafiyé, 166830
Novartis Investigative Site
Saida, 652
Colombia2 sites
Novartis Investigative Site
Bogotá
Novartis Investigative Site
Medellín, Antioquia
Czechia2 sites
Novartis Investigative Site
Olomouc, CZE, 775 20
Novartis Investigative Site
Prague, 12808
Australia1 site
Novartis Investigative Site
Kingswood, New South Wales, 2747
About this study
Official title: A Phase II Randomized, Double-blind Placebo Controlled, Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women With Hormone Receptor-positive HER2-negative Breast Cancer
The purpose of the study was to determine whether treatment with a PI3K inhibitor plus letrozole led to an increase in pathologic clinical response and Objective Response Rate compared to treatment with placebo plus letrozole in patients with Breast cancer.
- Conditions
- Breast Cancer
- Being tested
- alpelisib, buparlisib, Placebo
- Keywords
- BYL719, alpelisib, Breast Cancer, BKM120, buparlisib, Pathological Complete Response, neoadjuvant, hormone receptor-positive, HER2 negative, Objective Response Rate
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alpelisibDrug
Also called BYL719
BYL719 + Letrozole
buparlisibDrug
Also called BKM120
BKM120 + Letrozole
PlaceboDrug
Also called BYL719 Placebo, BKM120 Placebo
Placebo (of BYL719 or BKM120) + Letrozole
| Study group | Role | What they receive |
|---|---|---|
| Alpelisib + Letrozole | Experimental | Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily. Receives: Drug: alpelisib |
| Buparlisib + Letrozole | Experimental | Participants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily. Receives: Drug: buparlisib |
| Placebo + Letrozole | Placebo comparator | Participants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort
Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate.
Measured: After 24 weeks of treatment
Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Wild-type Cohort
Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate.
Measured: After 24 weeks of treatment
Objective Response Rate Per Investigator Assessment According to RECIST 1.1 for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
Objective Response Rate (ORR) defined as the proportion of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) based on local investigator's assessment according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1.
BOR was assessed per MRI or Ultrasound and defined as per RECIST 1.1 as CR for a disappearance of all non-nodal target lesions (TL)/non-target lesions (NTL) and a reduction in short axis to < 10 mm of any pathological lymph nodes assigned as TL/NTL and no new lesion; as PR if not qualifying for CR but with a decrease from baseline ≥ 30% in the sum of diameter of all TL, no progression of NTL and no new lesion.
Measured: After 24 weeks of treatment
Objective Response Rate According to RECIST 1.1 Per Investigator Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
Objective Response Rate (ORR) defined as the proportion of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) based on local investigator's assessment according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1.
BOR was assessed per MRI or Ultrasound and defined as per RECIST 1.1 as CR for a disappearance of all non-nodal target lesions (TL)/non-target lesions (NTL) and a reduction in short axis to < 10 mm of any pathological lymph nodes assigned as TL/NTL and no new lesion; as PR if not qualifying for CR but with a decrease from baseline ≥ 30% in the sum of diameter of all TL, no progression of NTL and no new lesion.
Measured: After 24 weeks of treatment
Secondary outcomes (28)
pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Mutant Cohort Based on ctDNA
pCR and Objective response rate according to RECIST 1.1 per investigator assessment after 24 weeks of treatment
Measured: After 24 weeks of treatment
pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Wild-type Cohort Based on ctDNA
pCR and Objective response rate according to RECIST 1.1 per investigator assessment after 24 weeks of treatment
Measured: After 24 weeks of treatment
Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
Breast conserving surgery is defined for participants who underwent surgery and did not have a mastectomy. The row "no surgery" provides the number of patients who did not undergo surgery at all for various reasons.
Measured: After 24 weeks of treatment
Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
Breast conserving surgery is defined as the percentage of participants with no mastectomy following completion of 24 weeks of treatment. Breast conserving surgery is defined for participants who underwent surgery and did not have a mastectomy. The row "no surgery" provides the number of patients who did not undergo surgery at all for various reasons.
Measured: After 24 weeks of treatment
Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR
Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR
Measured: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Non-responders as Per pCR
Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Non-responders as Per pCR.
Measured: Baseline, Cycle 1 Day 15 (each cycle is 28 days ) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Responders as Per pCR
Association between pCR and changes in Ki67 from baseline for alpelisib vs. placebo - PIK3CA wild-type cohort: responders as per pCR
Measured: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Non-responders as Per pCR
Association between pCR and changes in Ki67 from baseline for alpelisib vs. placebo - PIK3CA wild-type cohort: non-responders as per pCR
Measured: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
Preoperative endocrine prognostic index (PEPI) response as per central assessment for alpelisib vs. placebo - PIK3CA mutant cohort. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and ER status of the surgical specimen (Ellis et al, Contemp Clin Trials 2008). The PEPI score ranges from 0 to to 12, and a higher score means a worse outcome. PEPI response is defined as a PEPI score of 0.
Measured: At the time of surgery (expected after 24 weeks of treatment)
Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
Preoperative endocrine prognostic index (PEPI) response as per central assessment for alpelisib vs. placebo - PIK3CA wild-type cohort. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and ER status of the surgical specimen (Ellis et al, Contemp Clin Trials 2008). The PEPI score ranges from 0 to to 12, and a higher score means a worse outcome. PEPI response is defined as a PEPI score of 0.
Measured: At the time of surgery (expected after 24 weeks of treatment)
Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
Summary of primary PK parameters for alpelisib plasma concentration
Measured: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
Alpelisib PK Parameter: Cmax at Cycle 1 Day 1
Summary of primary PK parameters for alpelisib plasma concentration
Measured: Cycle 1 Day 1 (each cycle is 28 days)
Alpelisib and PK Parameter: Tmax at Cycle 1 Day 1
Summary of primary PK parameters for alpelisib plasma concentration
Measured: Cycle 1 Day 1 (each cycle is 28 days)
Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1
Summary of primary PK parameters for alpelisib plasma concentration
Measured: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
Alpelisib PK Parameter: Cmax at Cycle 4 Day 1
Summary of primary PK parameters for alpelisib plasma concentration
Measured: Cycle 4 Day 1 (each cycle is 28 days)
Alpelisib PK Parameter: Tmax at Cycle 4 Day 1
Summary of primary PK parameters for alpelisib plasma concentration
Measured: Cycle 4 Day 1 (each cycle is 28 days)
Letrozole and PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
Summary of primary PK parameters for Letrozole plasma concentration
Measured: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
Letrozole PK Parameter: Cmax at Cycle 1 Day 1
Summary of primary PK parameters for letrozole plasma concentration
Measured: Cycle 1 Day 1 (each cycle is 28 days)
Letrozole PK Parameter: Tmax at Cycle 1 Day 1
Summary of primary PK parameters for letrozole plasma concentration
Measured: Cycle 1 Day 1 (each cycle is 28 days)
Letrozole PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1
Summary of primary PK parameters for Letrozole plasma concentration
Measured: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
Letrozole PK Parameter: Cmax at Cycle 4 Day 1
Summary of primary PK parameters for letrozole plasma concentration
Measured: Cycle 4 Day 1 (each cycle is 28 days)
Letrozole PK Parameter: Tmax at Cycle 4 Day 1
Summary of primary PK parameters for letrozole plasma concentration
Measured: Cycle 4 Day 1 (each cycle is 28 days)
Buparlisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
Summary of primary PK parameters for Buparlisib plasma concentration
Measured: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
Buparlisib PK Parameter: Cmax at Cycle 1 Day 1
Summary of primary PK parameters for buparlisib plasma concentration
Measured: Cycle 1 Day 1 (each cycle is 28 days)
Buparlisib PK Parameter: Tmax at Cycle 1 Day 1
Summary of primary PK parameters for buparlisib plasma concentration
Measured: Cycle 1 Day 1 (each cycle is 28 days)
Buparlisib PK Parameter: AUClast at Cycle 4 Day 1
Summary of primary PK parameters for Buparlisib plasma concentration
Measured: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
Buparlisb PK Parameter: Cmax at Cycle 4 Day 1
Summary of primary PK parameters for buparlisib plasma concentration
Measured: Cycle 4 Day 1 (each cycle is 28 days)
Buparlisib PK Parameter: Tmax at Cycle 4 Day 1
Summary of primary PK parameters for buparlisib plasma concentration
Measured: Cycle 4 Day 1 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2013 (estimated)
- Study start11 Mar 2014
- Primary completion7 Jul 2017
- Study completion8 Jul 2017
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.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 340 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01923168
- Sponsor's protocol ID
- CBYL719A2201
- Other IDs
- 2013-001862-41
- Status last verified
- Aug 2018
- First submitted
- 13 Aug 2013
- Last updated
- 14 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Mayer IA, Prat A, Egle D, Blau S, Fidalgo JAP, Gnant M, Fasching PA, Colleoni M, Wolff AC, Winer EP, Singer CF, Hurvitz S, Estevez LG, van Dam PA, Kummel S, Mundhenke C, Holmes F, Babbar N, Charbonnier L, Diaz-Padilla I, Vogl FD, Sellami D, Arteaga CL. A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB). Clin Cancer Res. 2019 May 15;25(10):2975-2987. doi: 10.1158/1078-0432.CCR-18-3160. Epub 2019 Feb 5.
PubMed 30723140
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Randomized, Double-blind Placebo Controlled, Study of Letrozole With or Without BYL719 or Buparlisib, for the Neoadjuvant Treatment of Postmenopausal Women With Hormone Receptor-positive HER2-negative Breast Cancer
- ClinicalTrials.gov ID
- NCT01923168
- Acronym / sponsor ID
- CBYL719A2201
- Conditions
- Breast Cancer
- Keywords
- BYL719, alpelisib, Breast Cancer, BKM120, buparlisib, Pathological Complete Response, neoadjuvant, hormone receptor-positive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 340 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 11 Mar 2014 (actual)
- Primary completion
- 7 Jul 2017 (actual)
- Study completion
- 8 Jul 2017 (actual)
- First posted
- 15 Aug 2013 (estimated)
- Results
- Posted 14 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study was to determine whether treatment with a PI3K inhibitor plus letrozole led to an increase in pathologic clinical response and Objective Response Rate compared to treatment with placebo plus letrozole in patients with Breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Alpelisib + Letrozole | Experimental | Drug: alpelisibParticipants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily. |
| Buparlisib + Letrozole | Experimental | Drug: buparlisibParticipants took buparlisib 100 mg once daily or 5 days on/2 days off plus letrozole 2.5 mg once daily. |
| Placebo + Letrozole | Placebo comparator | Drug: PlaceboParticipants took matching Placebo (of alpelisib 300 mg once daily/buparlisib 100 mg once daily or 5 days on/2 days off) plus Letrozole 2.5 mg once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patient is an adult, female ≥ 18 years old at the time of informed consent
- Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer
- Patient is postmenopausal.
- Patient has T1c-T3, any N, M0, operable breast cancer
- Patients must have measurable disease
Key exclusion criteria (5 listed)
- Patient has locally recurrent or metastatic disease
- Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease before randomization.
- Patient with type 1 diabetes mellitus or not adequately controlled type 2 diabetes mellitus
- History of acute pancreatitis within 1 year of study entry
- Uncontrolled hypertension
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 |
|---|---|---|
| alpelisibAlso: BYL719BYL719 + Letrozole | Drug | Alpelisib + Letrozole |
| buparlisibAlso: BKM120BKM120 + Letrozole | Drug | Buparlisib + Letrozole |
| PlaceboAlso: BYL719 Placebo, BKM120 PlaceboPlacebo (of BYL719 or BKM120) + Letrozole | Drug | Placebo + Letrozole |
Primary outcome
Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort
Time frame: After 24 weeks of treatment
Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate.
Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Wild-type Cohort
Time frame: After 24 weeks of treatment
Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate.
Objective Response Rate Per Investigator Assessment According to RECIST 1.1 for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
Time frame: After 24 weeks of treatment
Objective Response Rate (ORR) defined as the proportion of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) based on local investigator's assessment according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1. BOR was assessed per MRI or Ultrasound and defined as per RECIST 1.1 as CR for a disappearance of all non-nodal target lesions (TL)/non-target lesions (NTL) and a reduction in short axis to < 10 mm of any pathological lymph nodes assigned as TL/NTL and no new lesion; as PR if not qualifying for CR but with a decrease from baseline ≥ 30% in the sum of diameter of all TL, no progression of NTL and no new lesion.
Objective Response Rate According to RECIST 1.1 Per Investigator Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
Time frame: After 24 weeks of treatment
Objective Response Rate (ORR) defined as the proportion of patients with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) based on local investigator's assessment according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1. BOR was assessed per MRI or Ultrasound and defined as per RECIST 1.1 as CR for a disappearance of all non-nodal target lesions (TL)/non-target lesions (NTL) and a reduction in short axis to < 10 mm of any pathological lymph nodes assigned as TL/NTL and no new lesion; as PR if not qualifying for CR but with a decrease from baseline ≥ 30% in the sum of diameter of all TL, no progression of NTL and no new lesion.
28 secondary outcomes
pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Mutant Cohort Based on ctDNA
Time frame: After 24 weeks of treatment
pCR and Objective Response Rate According to RECIST 1.1 Criteria Per Investigator Assessment for Alpelisib vs. Placebo in PIK3CA Wild-type Cohort Based on ctDNA
Time frame: After 24 weeks of treatment
Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
Time frame: After 24 weeks of treatment
Rate of Breast Conserving Surgery for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
Time frame: After 24 weeks of treatment
Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Responders as Per pCR
Time frame: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Mutant Cohort: Non-responders as Per pCR
Time frame: Baseline, Cycle 1 Day 15 (each cycle is 28 days ) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Responders as Per pCR
Time frame: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Association Between pCR and Changes in Ki67 From Baseline for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort: Non-responders as Per pCR
Time frame: Baseline, Cycle 1 Day 15 (each cycle is 28 days) and surgery (End of Treatment (EOT) expected after 24 weeks of treatment)
Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Mutant Cohort
Time frame: At the time of surgery (expected after 24 weeks of treatment)
Preoperative Endocrine Prognostic Index (PEPI) Response as Per Central Assessment for Alpelisib vs. Placebo - PIK3CA Wild-type Cohort
Time frame: At the time of surgery (expected after 24 weeks of treatment)
Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
Time frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
Alpelisib PK Parameter: Cmax at Cycle 1 Day 1
Time frame: Cycle 1 Day 1 (each cycle is 28 days)
Alpelisib and PK Parameter: Tmax at Cycle 1 Day 1
Time frame: Cycle 1 Day 1 (each cycle is 28 days)
Alpelisib PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1
Time frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
Alpelisib PK Parameter: Cmax at Cycle 4 Day 1
Time frame: Cycle 4 Day 1 (each cycle is 28 days)
Alpelisib PK Parameter: Tmax at Cycle 4 Day 1
Time frame: Cycle 4 Day 1 (each cycle is 28 days)
Letrozole and PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
Time frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
Letrozole PK Parameter: Cmax at Cycle 1 Day 1
Time frame: Cycle 1 Day 1 (each cycle is 28 days)
Letrozole PK Parameter: Tmax at Cycle 1 Day 1
Time frame: Cycle 1 Day 1 (each cycle is 28 days)
Letrozole PK Parameters: AUC0-24, AUClast at Cycle 4 Day 1
Time frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
Letrozole PK Parameter: Cmax at Cycle 4 Day 1
Time frame: Cycle 4 Day 1 (each cycle is 28 days)
Letrozole PK Parameter: Tmax at Cycle 4 Day 1
Time frame: Cycle 4 Day 1 (each cycle is 28 days)
Buparlisib PK Parameters: AUC0-24, AUClast at Cycle 1 Day 1
Time frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 1 Day 1 (each cycle is 28 days)
Buparlisib PK Parameter: Cmax at Cycle 1 Day 1
Time frame: Cycle 1 Day 1 (each cycle is 28 days)
Buparlisib PK Parameter: Tmax at Cycle 1 Day 1
Time frame: Cycle 1 Day 1 (each cycle is 28 days)
Buparlisib PK Parameter: AUClast at Cycle 4 Day 1
Time frame: 0, 0.5, 1, 3, 6, 9 and 24 hours post-dose at Cycle 4 Day 1 (each cycle is 28 days)
Buparlisb PK Parameter: Cmax at Cycle 4 Day 1
Time frame: Cycle 4 Day 1 (each cycle is 28 days)
Buparlisib PK Parameter: Tmax at Cycle 4 Day 1
Time frame: Cycle 4 Day 1 (each cycle is 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30723140Mayer IA, Prat A, Egle D, Blau S, Fidalgo JAP, Gnant M, Fasching PA, Colleoni M, Wolff AC, Winer EP, Singer CF, Hurvitz S, Estevez LG, van Dam PA, Kummel S, Mundhenke C, Holmes F, Babbar N, Charbonnier L, Diaz-Padilla I, Vogl FD, Sellami D, Arteaga CL. A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB). Clin Cancer Res. 2019 May 15;25(10):2975-2987. doi: 10.1158/1078-0432.CCR-18-3160. Epub 2019 Feb 5.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
86 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing alpelisib and buparlisib in people with Breast Cancer, run by Novartis Pharmaceuticals at 86 sites in 17 countries.
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 8 inclusion and 5 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 14 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 86 sites in United States, Spain, Austria, Japan, Brazil and 12 more countries. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 14 Sep 2018). 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?
Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort (time frame: After 24 weeks of treatment). The study lists 4 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 NCT01923168, 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 14 Sep 2018.