| Eligibility |
Inclusion Criteria:
- Patient eligible for inclusion in this Treatment Plan have to meet all of the
following criteria:
1. Patient has signed the Informed Consent (ICF) prior to any eligibility
evaluations being performed and is able to comply with protocol requirements
2. Patient is an adult and = 18 years old at the time of informed consent
3. Patient has locally advanced or metastatic cancer resistant or refractory to
available standard of care treatment options and has no other available
comparable or satisfactory alternative treatment options
4. PIK3CA mutation, or other molecular alteration known to activate PI3K, in tumor
tissue as determined by a standard Laboratory
5. Patient is not eligible for participation in any ongoing clinical trials with
alpelisib, or has recently completed a clinical trial with alpelisib that has
been terminated, and after considering other options (e.g. trial extensions,
amendments, etc.), the treating physician has determined that treatment is
necessary and there are no other feasible alternatives for the patient
6. Patient is not being transferred from an ongoing clinical trial for which they
are still eligible
7. Patient has adequate bone marrow and organ function as defined by the following
laboratory values:
1. Absolute Neutrophil Count (ANC) = 1.5 x 109/L
2. Platelets = 100 x 109/L (For patients with hematologic malignancies
involving the bone marrow, platelet count > 75 x 109/L may be acceptable)
3. Hemoglobin = 9.0 g/dL
4. INR = 1.5
5. Potassium, magnesium and calcium (corrected for albumin), within normal
limits for the institution, or = Grade 1 severity according to NCI-CTCAE
version 4.03 if judged clinically not significant by the investigator
6. Serum creatinine = 1.5 x ULN and/or creatinine clearance > 50% LLN (Lower
Limit of Normal)
7. Total serum bilirubin < ULN (or = 1.5 x ULN if liver metastases are present;
or total bilirubin = 3.0 x ULN with direct bilirubin within normal range in
patients with well documented Gilbert's Syndrome, (defined as presence of
several episodes of unconjugated hyperbilirubinemia with normal CBC results
including normal reticulocyte count and peripheral blood smear, normal liver
function test results, and absence of other contributing disease processes
at the time of diagnosis)
8. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) = 2.5
ULN (or < 5.0 x ULN if liver metastases are present)
8. Patient is deemed by the Treating Physician to have the initiative and means to
be compliant with the treatment plan (treatment and follow-up requested by the
Treating Physician)
Exclusion Criteria:
- Patients eligible for this Treatment Plan must not meet any of the following criteria:
1. Patient has history of hypersensitivity to any drugs or metabolites of similar
chemical classes as alpelisib
2. Patient has not recovered to grade 1 or better (except alopecia) from related
side effects of any prior antineoplastic therapy
3. Patient has had major surgery within 4 weks prior to starting treatment with
alpelisib or has not recovered from major side effects
4. Patient is currently receiving or has received systemic corticosteroids = 2 weeks
prior to starting treatment with alpelisib, or has not fully recovered from side
effects of such treatment
5. Patient with clinically manifest diabetes mellitus, or documented steroid induced
diabetes mellitus
6. Patient is being treated at start of treatment with alpelisib with any of the
following drugs:
Drugs known to be strong inhibitors or inducers of isoenzyme CYP3A4 including
herbal medications, or drugs with a known risk to induce Torsades de Pointes (See
Appendix 1, Table 2 for a full list of prohibited medications).
Note: The patient must have discontinued strong inducers for at least one week
and must have discontinued strong inhibitors before the treatment with alpelisib
is initiated. Switching to a different medication prior to starting treatment
with alpelisib is allowed.
7. Patient 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.
8. Patients who have other concurrent severe and/or uncontrolled medical conditions
that would, in the Treating Physician's judgment, contraindicate patient
participation in the individual patient program (eg. active or uncontrolled
severe infection, chronic active hepatitis, immuno-compromised, acute or chronic
pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc.)
9. Patient has a known history of HIV infection (testing not mandatory) infection
10. Patient has any of the following cardiac abnormalities:
a. Symptomatic congestive heart failure i. History of documented congestive heart
failure (New York Heart Association functional classification III-IV), documented
cardiomyopathy ii. Left Ventricular Ejection Fraction (LVEF) <50% as determined
by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) b. Myocardial
infarction = 6 months prior to enrolment c. Unstable angina pectoris Acute
coronary angioplasty, or stenting), < 3 months prior to screening coronary
syndromes (including myocardial infarction, unstable angina, coronary artery
bypass graft (CABG).
d. Serious uncontrolled cardiac arrhythmia History or current evidence of
clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction
abnormality, e.g. congenital long QT syndrome, high-grade/complete AV-blockage:
per guidelines.
e. Symptomatic pericarditis f. QTcF > 480 msec on the screening ECG (using the
QTcF formula) currently receiving treatment with medication that has a known risk
to prolong the QT interval or inducing Torsades de Pointes, and the treatment
cannot be discontinued or switched to a different medication prior to starting
treatment with alpelisib.
11. Patient has impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of alpelisib (e.g., ulcerative diseases,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
resection)
12. Patient has other prior or concurrent malignancy (except for the following:
adequately treated basal cell or squamous cell skin cancer, or other adequately
treated in situ cancer, early gastric or GI cancer resected completely by
endoscopy procedures or any other cancer from which the patient has been disease
free for = 3 years)
13. Patient has a history of non-compliance to medical regimen or inability to grant
consent
14. Patient who does not apply highly effective contraception during the treatment
with alpelisib and through the duration as defined below after the final dose of
alpelisib:
1. Sexually active males should use a condom during intercourse while taking
drug and for 4 weeks* after the final dose of alpelisib and should not
father a child in this period, but may be recommended to seek advice on
conservation of sperm. A condom is required to be used also by vasectomized
men in order to prevent delivery of the drug via seminal fluid.
2. Women of child-bearing potential, defined as all female physiologically
capable of becoming pregnant, must use highly effective contraception during
the IPP and through at least 4 weeks* after the final dose of alpelisib
3. Highly effective contraception is defined as either:
i. Total abstinence: When this is in line with the preferred and usual lifestyle
of the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal,
postovulation methods) and withdrawal are not acceptable methods of
contraception].
ii. Female sterilization: have had surgical bilateral oophorectomy (with or
without hysterectomy), total hysterectomy or tubal ligation at least six weeks
before starting treatment with alpelisib. In case of oophorectomy alone, only
when the reproductive status of the woman has been confirmed by follow up hormone
level assessment iii. Male partner sterilization (with the appropriate
post-vasectomy documentation of the absence of sperm in the ejaculate). [For
female patients participating to this IPP, the vasectomized male partner should
be the sole partner for that patient] iv. Use a combination of the following
(both a+b):
1. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
2. Barrier methods of contraception: Condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal
suppository.
Note: Hormonal contraception methods (e.g. oral, injected, and implanted) are not
allowed as alpelisibBYL719 may decrease the effectiveness of hormonal
contraceptives.
* Please consult your local product labels should any concomitant medications be
used, as this period may be longer for other potentially genotoxic compounds.
A female is considered post-menopausal and not of child-bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have
had surgical bilateral oophorectomy (with or without hysterectomy) at least six
weeks ago before the treatment start. For females with therapy-induced
amenorrhea, oophorectomy or serial measurements of Follicle-Stimulating Hormone
(FSH) and/or estradiol are needed to ensure postmenopausal status.
NOTE: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone
(LHRH) agonist (goserelin acetate or leuprolide acetate) is not permitted for
induction of ovarian suppression.
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