SF1126 in Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes

Brief Title

SF1126 in Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes

Official Title

A Phase II Open Label Study of the PI3 Kinase (PI-3) Inhibitor, SF1126, in Patients With Recurrent or Progressive SCCHN and Mutations in PIK3CA Gene and/or PI-3 Kinase Pathway Genes

Brief 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.
    

Detailed Description

      SignalRx Pharmaceuticals has developed a pan isoform specific PI-3 inhibitor called SF1126 to
      treat patients with advanced or metastatic cancer. SF1126 is a conjugate that contains two
      components: SF1101 (the active drug) and SF1174 (an inactive tetrapeptide RGD targeting
      moiety)

      Both components of SF1126 play key roles in the activity of the drug. SF1101 is a selective
      inhibitor of certain members of the phosphatidyl inositol 3-kinase (PI-3) family and SF1174
      binds selectively to receptors known to be present on neovasculature supporting tumors and on
      some tumor cells themselves. These components result in a drug designed to be both selective
      in its activity and targeted in its delivery.

      This is an open label Phase II study of SF1126 in adult patients with recurrent or refractory
      advanced SCCHN with PIK3CA mutation. Treatment cycles (28 days) will consist of SF1126 1110
      mg/m2 administered intravenously (IV) twice per week (separated by at least three days) for
      the first four cycles and then once weekly for subsequent cycles.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

To Determine ORR

Secondary Outcome

 Number of Participants With Treatment-related Adverse Events

Condition

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma

Intervention

SF1126

Study Arms / Comparison Groups

 SF1126
Description:  SF1126 1110 mg/m2 administered intravenously (IV) twice per week (separated by at least three days) for the first four treatment cycles (28 days) and then once weekly for subsequent cycles.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

1

Start Date

November 2016

Completion Date

December 2016

Primary Completion Date

December 2016

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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Ezra Cohen, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02644122

Organization ID

140904


Responsible Party

Sponsor-Investigator

Study Sponsor

Ezra Cohen

Collaborators

 SignalRX Pharmaceuticals, Inc.

Study Sponsor

Ezra Cohen, MD, Principal Investigator, University of California, San Diego


Verification Date

June 2018