<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04473040</url>
  </required_header>
  <id_info>
    <org_study_id>CBYL719C2001M</org_study_id>
    <nct_id>NCT04473040</nct_id>
  </id_info>
  <brief_title>Managed Access Program to Provide Access to Alpelisib for Patients With Advanced Breast Cancer</brief_title>
  <official_title>Managed Access Program (MAP) Cohort Treatment Plan CBYL719C2001M to Provide Access to Alpelisib (BYL719) for Patients With HR-positive, HER2-negative Advanced Breast Cancer With Mutated Phosphoinositide 3-kinase Who Progressed on or After AI Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <brief_summary>
    <textblock>
      The purpose of this Cohort Treatment Plan is to allow access to alpelisib for patients&#xD;
      diagnosed with HR-positive, HER2-negative advanced breast cancer with mutated&#xD;
      phosphoinositide 3-kinase who progressed on or after AI treatment. The patient's Treating&#xD;
      Physician should follow the suggested treatment guidelines and comply with all local health&#xD;
      authority regulations.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Available</overall_status>
  <study_type>Expanded Access</study_type>
  <has_expanded_access>No</has_expanded_access>
  <expanded_access_info>
    <expanded_access_type_intermediate>Yes</expanded_access_type_intermediate>
  </expanded_access_info>
  <condition>HR+, HER2-, Advanced Breast Cancer</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>alpelisib</intervention_name>
    <description>Alpelisib is provided as 50 mg and 200 mg film coated tablets as individual patient supply, packaged in bottles. Alpelisib will be dosed on a flat scale of mg/day and not be adjusted to body weight or body surface area. Alpelisib will be administered at a starting dose of 300 mg orally once daily on a continuous dosing schedule and can be adjusted for toxicity per the recommendations in this treatment plan.</description>
    <other_name>BYL719</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients eligible for inclusion in this Treatment Plan have to meet all of the following&#xD;
        criteria:&#xD;
&#xD;
        Written patient informed consent must be obtained prior to start of treatment.&#xD;
&#xD;
          1. Patient is an adult male or female (≥ 18 years of age) with advanced (locoregionally&#xD;
             recurrent not amenable to curative therapy or metastatic) hormone receptor-positive,&#xD;
             HER2-negative breast cancer&#xD;
&#xD;
          2. Patient has documented evidence of a mutation in the PIK3CA gene as determined in&#xD;
             tumor tissue or plasma by a local laboratory.&#xD;
&#xD;
          3. If female, then the patient is postmenopausal. Postmenopausal status is defined either&#xD;
             by:&#xD;
&#xD;
               -  Prior bilateral oophorectomy&#xD;
&#xD;
               -  Age ≥60&#xD;
&#xD;
               -  Age &lt;60 and amenorrheic for ≥12 months in the absence of chemotherapy, tamoxifen,&#xD;
                  toremifene, or ovarian suppression and Follicle-stimulating Hormone (FSH) and&#xD;
                  estradiol in the postmenopausal range per local normal range&#xD;
&#xD;
          4. Patient has evidence of recurrence or progression during or after AI therapy (i.e.&#xD;
             letrozole, anastrozole, exemestane). AI therapy does not need to be the latest&#xD;
             treatment regimen.&#xD;
&#xD;
          5. Patient has a histologically and/or cytologically confirmed diagnosis of ER+ and/or&#xD;
             PgR+ breast cancer by local laboratory.&#xD;
&#xD;
          6. Patient has adequate bone marrow and organ function as defined by laboratory values:&#xD;
&#xD;
               -  Fasting plasma glucose (FPG) ≤ 140 mg/dL (7.7 mmol/L) and Glycosylated Hemoglobin&#xD;
                  (HbA1c) ≤ 6.4% (both criteria have to be met)&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
        Patients eligible for this Treatment Plan must not meet any of the following criteria:&#xD;
&#xD;
          1. Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor.&#xD;
&#xD;
          2. Participant has a known hypersensitivity to alpelisib, or to any of the excipients of&#xD;
             alpelisib.&#xD;
&#xD;
          3. Participant has had major surgery within 14 days prior to treatment start and/or has&#xD;
             not recovered from major side effects.&#xD;
&#xD;
          4. Participant with an established diagnosis of diabetes mellitus type I or not&#xD;
             controlled type II (based on FG and HbA1c).&#xD;
&#xD;
          5. Participant has impairment of gastrointestinal (GI) function or GI disease that may&#xD;
             significantly alter the absorption of the drugs (e.g., ulcerative diseases,&#xD;
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel&#xD;
             resection) based on physician discretion.&#xD;
&#xD;
          6. Participant has currently documented pneumonitis/interstitial lung disease (the chest&#xD;
             CT scan performed before start of treatment for the purpose of tumor assessment should&#xD;
             be reviewed to confirm that there are no relevant pulmonary complications present).&#xD;
&#xD;
          7. Participant with Child Pugh score B or C.&#xD;
&#xD;
          8. Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mmHg and/or&#xD;
             Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without anti-hypertensive&#xD;
             medication. Initiation or adjustment of antihypertensive medication(s) is allowed&#xD;
             prior to screening.&#xD;
&#xD;
          9. Participant has clinically significant, uncontrolled heart disease and/or recent&#xD;
             cardiac events including any of the following:&#xD;
&#xD;
               -  History of angina pectoris, coronary artery bypass graft (CABG), symptomatic&#xD;
                  pericarditis, or myocardial infarction within 6 months prior to the start of&#xD;
                  treatment&#xD;
&#xD;
               -  History of documented congestive heart failure (New York Heart Association&#xD;
                  functional classification III-IV)&#xD;
&#xD;
               -  Left Ventricular Ejection Fraction (LVEF) &lt; 50% at screening as determined by&#xD;
                  Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)&#xD;
&#xD;
               -  Clinically significant cardiac arrhythmias, (e.g., ventricular tachycardia),&#xD;
                  complete left bundle branch block, high grade AV block (e.g. bifascicular block,&#xD;
                  Mobitz type II and third degree AV block without pacemaker in place&#xD;
&#xD;
               -  Long QT syndrome, family history of idiopathic sudden death or congenital long QT&#xD;
                  syndrome, or Fridericia QT correction formula (QTcF) &gt; 470 msec at screening&#xD;
                  (mean of triplicate ECGs).&#xD;
&#xD;
         10. Participant has any other concurrent severe and/or uncontrolled medical condition that&#xD;
             would, in the physician's judgment, contraindicate participation in the MAP (e.g.,&#xD;
             chronic active hepatitis [testing not mandatory unless required by local regulations&#xD;
             or requirements], severe hepatic impairment, etc.).&#xD;
&#xD;
         11. Participant is currently receiving any of the following medications and cannot be&#xD;
             discontinued 7 days prior to the start of the treatment:&#xD;
&#xD;
               -  Strong CYP3A4 inducers&#xD;
&#xD;
               -  Inhibitors of BCRP.&#xD;
&#xD;
         12. Participant has a history of acute pancreatitis within 1 year of screening or past&#xD;
             medical history of chronic pancreatitis.&#xD;
&#xD;
         13. Participant with unresolved osteonecrosis of the jaw.&#xD;
&#xD;
         14. Participant has a history of severe cutaneous reaction, such as Stevens-Johnson&#xD;
             Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug&#xD;
             Reaction with Eosinophilia and Systemic Symptoms (DRESS).&#xD;
&#xD;
         15. Participant has received radiotherapy ≤ 4 weeks or limited field radiation for&#xD;
             palliation ≤ 2 weeks prior to treatment, and who has not recovered to grade 1 or&#xD;
             better from related side effects of such therapy (with the exception of alopecia).&#xD;
&#xD;
         16. Participant is currently receiving or has received systemic corticosteroids ≤ 2 weeks&#xD;
             prior to starting drug, or who have not fully recovered from side effects of such&#xD;
             treatment. Note: The following uses of corticosteroids are permitted: single doses,&#xD;
             topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways&#xD;
             diseases), eye drops or local injections (e.g., intra-articular).&#xD;
&#xD;
         17. Participant has not recovered from all toxicities related to prior anticancer&#xD;
             therapies to NCI CTCAE version 4.03 Grade ≤1. Exception to this criterion: participant&#xD;
             with any grade of alopecia are allowed to enter the MAP.&#xD;
&#xD;
         18. Participant has a concurrent malignancy or malignancy within 3 years of start of&#xD;
             treatment, with the exception of adequately treated, basal or squamous cell carcinoma,&#xD;
             non-melanomatous skin cancer, or curatively resected cervical cancer.&#xD;
&#xD;
         19. Participant has central nervous system (CNS) involvement which was not previously&#xD;
             treated and not fulfilling the following 3 criteria to be eligible for the MAP:&#xD;
&#xD;
               -  Completed prior therapy (including radiation and/or surgery) for CNS metastases ≥&#xD;
                  28 days prior to the treatment and&#xD;
&#xD;
               -  CNS tumor is clinically stable at the time of treatment start and&#xD;
&#xD;
               -  Participant is not receiving steroids and/or enzyme inducing anti-epileptic&#xD;
                  medications for brain metastases.&#xD;
&#xD;
         20. Subject has any other concurrent severe and/or uncontrolled medical condition that&#xD;
             would, in the physician's judgment, contraindicate subject participation in MAP (e.g.,&#xD;
             chronic active hepatitis [testing not mandatory unless required by local regulations&#xD;
             or requirements], severe hepatic impairment.&#xD;
&#xD;
         21. Participant is not able to understand and to comply with instructions and&#xD;
             requirements, including oral administration of treatment.&#xD;
&#xD;
         22. Participant is a nursing (lactating) or pregnant as confirmed by a positive serum&#xD;
             (hCG) test prior to initiating treatment.&#xD;
&#xD;
         23. Participant is a woman of child-bearing potential defined as all women physiologically&#xD;
             capable of becoming pregnant, unless they are using highly effective methods of&#xD;
             contraception during treatment and at least for 1 week after the last dose of the&#xD;
             treatment. Highly effective contraception methods include:&#xD;
&#xD;
               -  Total abstinence (when this is in line with the preferred and usual lifestyle of&#xD;
                  the participant). Periodic abstinence (e.g., calendar, ovulation, symptothermal,&#xD;
                  postovulation methods) and withdrawal are not acceptable methods of contraception&#xD;
&#xD;
               -  Female sterilization (have had surgical bilateral oophorectomy with or without&#xD;
                  hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks&#xD;
                  before taking treatment. In case of oophorectomy alone, only when the&#xD;
                  reproductive status of the woman has been confirmed by follow up hormone level&#xD;
                  assessment&#xD;
&#xD;
               -  Male sterilization (at least 6 months prior to screening). For female&#xD;
                  participants the vasectomized male partner should be the sole partner for that&#xD;
                  participant&#xD;
&#xD;
               -  Use of oral (estrogen and progesterone), injected or implanted combined hormonal&#xD;
                  method of contraception or placement of an intrauterine device (IUD) or&#xD;
                  intrauterine system (IUS), or forms of hormonal contraception that have&#xD;
                  comparable efficacy (failure rate &lt;1%), for example hormonal vaginal ring or&#xD;
                  transdermal hormone contraception. In case of use or oral contraception, women&#xD;
                  should have been stable on the same pill for a minimum of 3 months before taking&#xD;
                  treatment.&#xD;
&#xD;
             Note: Women are considered postmenopausal and not of child bearing potential if they&#xD;
             have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical&#xD;
             profile (i.e., age appropriate, history of vasomotor symptoms) or have had surgical&#xD;
             bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or&#xD;
             bilateral tubal ligation at least 6 weeks before starting treatment In the case of&#xD;
             oophorectomy alone, only when the reproductive status of the woman has been confirmed&#xD;
             by follow up hormone level assessment is she considered not of child bearing&#xD;
             potential.&#xD;
&#xD;
             If local regulations to prevent pregnancy deviate from the contraception methods&#xD;
             listed above, local regulations apply and will be described in the informed consent&#xD;
             form (ICF).&#xD;
&#xD;
         24. Participant is a sexually active male unwilling to use a condom during intercourse&#xD;
             while taking treatment, and for 1 week after the last dose of treatment. A condom is&#xD;
             required for all sexually active male participants to prevent them from fathering a&#xD;
             child AND to prevent delivery of treatment via seminal fluid to their partner. In&#xD;
             addition, male participants must not donate sperm during MAP and up to the time period&#xD;
             specified above.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Novartis Pharmaceuticals</last_name>
    <phone>1-888-669-6682</phone>
    <email>novartis.email@novartis.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Novartis Pharmaceuticals</last_name>
    <phone>+41613241111</phone>
  </overall_contact_backup>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>February 13, 2023</last_update_submitted>
  <last_update_submitted_qc>February 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BYL719</keyword>
  <keyword>hormone receptor positive</keyword>
  <keyword>HER2-negative</keyword>
  <keyword>breast cancer</keyword>
  <keyword>PIK3CA gene</keyword>
  <keyword>alpelisib</keyword>
  <keyword>Expanded access</keyword>
  <keyword>advanced breast cancer</keyword>
  <keyword>stage IV</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04473040
org study id: CBYL719C2001M
nct id: NCT04473040
lead sponsor: 
The purpose of this Cohort Treatment Plan is to allow access to alpelisib for patients
      diagnosed with HR-positive, HER2-negative advanced breast cancer with mutated
      phosphoinositide 3-kinase who progressed on or after AI treatment. The patient's Treating
      Physician should follow the suggested treatment guidelines and comply with all local health
      authority regulations.
expanded access type intermediate: Yes
intervention type: Drug
intervention name: alpelisib
description: Alpelisib is provided as 50 mg and 200 mg film coated tablets as individual patient supply, packaged in bottles. Alpelisib will be dosed on a flat scale of mg/day and not be adjusted to body weight or body surface area. Alpelisib will be administered at a starting dose of 300 mg orally once daily on a continuous dosing schedule and can be adjusted for toxicity per the recommendations in this treatment plan.
other name: BYL719
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Novartis Pharmaceuticals
phone: 1-888-669-6682
email: novartis.email@novartis.com
last name: Novartis Pharmaceuticals
phone: +41613241111
responsible party type: Sponsor
mesh term: Breast Neoplasms