SF1126 in Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes
Condition: Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
MeSH terms: Carcinoma, Squamous Cell
Intervention: SF1126
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: advanced cancer; metastatic cancer; Squamous Cell Carcinoma of the Head and Neck; SCCHN; gene mutation; PIK3R1, PIK3R5 and PIK3AP1; PIK3CG; AKT and mTOR; PIK3CA gene; PI-3 kinase inhibitor; PI-3 kinase pathway genes

Summary:

      The purpose of this study is to test the good and bad effects of an experimental drug called
      SF1126. This drug is being tested in patients whose cancer has not been controlled by
      available standard therapies and who have certain genes in their tumor.

      SF1126 is a drug that inhibits a cell protein called phosphatidyl inositol 3 kinase (PI3K).
      PI3K is part of signaling pathway that tells cancer cells to grow, survive, invade and
      metastasize. PI3K also has an important role in the development of blood vessels that are
      required to support tumor growth. SF1126 is being developed by SignalRx Pharmaceuticals, Inc.
      It is considered an experimental drug because it is not approved by the FDA for any disease
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of recurrent or metastatic SCCHN or any site except lip, thyroid, salivary
             gland, or nasopharynx.

          -  No known FDA-approved therapy available that's expected to prolong survival by greater
             than 3 months.

          -  Tumors with at least one of the following known mutations in the PI-3K signaling
             pathway, via assays performed in a CLIA-approved setting (Foundation Medicine
             FoundationOne test will be used. This assay uses a cut-off of 5% allele fraction for
             mutations. Allele fraction will be requested on each sample):

               1. PIK3CA,

               2. PIK3CG,

               3. PIK3R1, PIK3R5 and PIK3AP1 (regulatory subunits),

               4. AKT and mTOR, or

               5. PTEN Note: PIK3CA amplification is not eligible.

          -  Prior receipt of platinum-containing chemotherapy for recurrent/metastatic disease or
             a history of progression of disease within 6 months of receiving platinum as part of
             concurrent chemoradiation.

          -  Disease must not be amenable to potentially curative treatment..

          -  Has recovered from the acute toxic effects of all prior chemotherapy, immunotherapy,
             or radiotherapy.

               -  Myelosuppressive chemotherapy: At least 3 weeks since completion (6 weeks for
                  nitrosourea)

               -  Biologic (anti-neoplastic agent): At least 14 days since completion of therapy
                  with a biologic agent.

               -  Radiation (XRT):1 week must have elapsed from prior palliative XRT to non-target
                  lesions.

          -  Adequate Bone Marrow Function Defined for all subjects (including status post SCT):

               -  Peripheral absolute neutrophil count (ANC) 1000/mm3; Note: must be >7 days from
                  use of hematopoietic growth factor or 21 days from pegfilgastrim

               -  Platelet count 75,000/ mm3 (transfusion independent for >7 days)

               -  Hemoglobin 8.0 g/dL (may receive transfusions)

          -  Adequate Renal Function Defined As:

               -  Serum creatinine ≤ 1.5 x institution's ULN (upper limit of normal), or

               -  Creatinine clearance 50 ml/min

          -  Adequate Liver and Pancreatic Function Defined As:

               -  Total bilirubin 1.5 x upper limit of normal, and

               -  ALT or AST 5 x upper limit of normal, and

               -  Albumin 2 g/dL

          -  Adequate Central Nervous System Function Defined As:

               -  Subjects with seizure disorder may be enrolled if on anticonvulsants and seizures
                  are well controlled.

        Exclusion Criteria:

          -  Brain metastases or spinal cord compression, unless treatment was completed at least 4
             weeks before study entry, and stable without steroid treatment for at least 4 weeks.

          -  Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
             respiratory, cardiac [including life threatening arrhythmias], hepatic, or renal
             disease).

          -  Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy except alopecia
             or long-term radiation toxicity (radiation related toxicity 3 months or greater after
             radiation exposure).

          -  Presence of cardiac impairment defined as:

               -  Prior history of cardiovascular disease including heart failure that meets New
                  York Hearth Association (NYHA) class III and IV definitions; OR

               -  History of myocardial infarction/active ischemic heart disease within one year of
                  study entry; OR

               -  Uncontrolled dysrhythmias; OR

               -  Poorly controlled angina.

          -  Participation in a trial of an investigational agent within the prior 30 days.

          -  Pregnant or breast-feeding females.

          -  History of other malignancies except curatively excised carcinoma in situ of the
             cervix, non-melanomatous skin carcinoma or superficial bladder cancer or other solid
             tumors curatively treated with no evidence of disease for 3 years. Other cases will be
             reviewed and possibly allowed if discussed with and approved by the Principal
             Investigator.

          -  Patients receiving therapeutic doses of warfarin.

          -  Blood pressure greater than 170/90 or two standard deviations from normal based on age
             and weight nomogram on three separate measurements.