Single-arm Study With Bimiralisib in Patients With HNSCC Harboring NOTCH1 Loss of Function Mutations
Condition: HNSCC
MeSH terms: Squamous Cell Carcinoma of Head and Neck
Intervention: Bimiralisib
Intervention description: Bimiralisib capsules
Intervention MeSH terms: MTOR Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Oral administration
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Squamous Cell Carcinoma; Notch 1 loss of function mutation; PI3K/mTOR Inhibitor; Refractory metastatic

Summary:

      Preclinical data and limited clinical evidence suggest that Head and Neck Squameous Cell
      Carcinoma tumors harboring certain mutations may respond well to PI3K/mTOR inhibition
      (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibition).

      The current study enrolls patients with refractory and / or metastatic Head and Neck
      Squameous Cell Carcinoma based on the mutational status of their disease to assess the
      response to treatment with bimiralisib, an orally available pan-PI3K/mTOR inhibitor
      (phosphatidylinositol-3-kinase/ mammalian target of rapamycin inhibitor).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically or cytological confirmed diagnosis of Head and Neck Squameous Cell
             Carcinoma, for which no standard curative or life prolonging therapy is available

          2. Available CLIA-certified sequencing results of the NOTCH gene in Head and Neck
             Squameous Cell Carcinoma (HNSCC) tumor material. The tumor must harbor a NOTCH1 LOF
             mutation as confirmed by central review (MD Anderson Cancer Center, MDACC)

          3. ECOG performance status of ≤ 2

          4. Adequate bone marrow, liver, and renal functions

          5. Measurable disease according to RECIST version 1.1

          6. Patients of reproductive potential must agree to use effective contraception from
             screening until 90 days after discontinuing study treatment.

        Exclusion Criteria:

          1. Has received any anti-cancer treatment including hormonal and investigational agents
             within 21 days prior to first dose of bimiralisib.

          2. Major surgery within 28 days prior to first dose of bimiralisib or persisting side
             effects that have not improved to NCI-CTCAE grade 1 or better.

          3. Pregnant or nursing (lactating) women.

          4. Poorly controlled diabetes mellitus, steroid-induced diabetes mellitus

          5. Has other active malignancies that require systemic treatment.

          6. Has a known history of HIV infection

          7. Any of the following cardiac abnormalities:

               -  History of, or current, documented congestive heart failure (New York heart
                  association functional classification iii - iv), documented cardiomyopathy

               -  Symptomatic (NYHA class II or higher) left ventricular ejection fraction (LVEF) <
                  40% as determined by multiple gated acquisition (MUGA) scan or echocardiogram
                  (echo)

               -  Myocardial infarction ≤ 6 months prior to enrolment

               -  Unstable angina pectoris

               -  Serious uncontrolled cardiac arrhythmia

               -  Symptomatic pericarditis

          8. Impaired gastrointestinal (GI) function or GI disease that may significantly alter the
             absorption of study drug.

          9. Patient has a history of non-compliance to medical regimen or inability to grant
             consent.

         10. Medically documented history of an active major depressive episode, bipolar disorder
             (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt
             or ideation, or homicidal ideation (immediate risk of doing harm to others) or ≥ CTCAE
             grade 3 anxiety

         11. History of interstitial pneumonitis or patients who require chronic oxygen
             supplementation.