Treatment With Nab-paclitaxel in Cutaneous SCC
Condition: Cutaneous Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell
Intervention: nab-paclitaxel
Intervention description: nab-paclitaxel (abraxane) administered weekly (days 1,8, and 15 of 28 day cycle) to patients with unresectable locoregional or distantly metastatic cutaneous squamous cell carcinoma (SCC).
Intervention MeSH terms: Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cutaneous squamous cell carcinoma; SCC; abraxane; nab-paclitaxel; unresectable; metastatic

Summary:

      This is an investigator initiated phase II study to assess the efficacy of a chemotherapy
      called nab-paclitaxel as first line cytotoxic chemotherapy in subjects with unresectable
      locally advanced or metastatic cutaneous squamous cell carcinoma (SCC). All subjects receive
      the treatment by vein weekly and receive the same dose of the treatment.

      The risk of developing cutaneous SCC is approximately 10% in a lifetime. The vast majority
      are treated surgically and do not recur. However a small percentage become unresectable over
      time or metastasize distantly in the body. Unresectable and metastatic cutaneous SCC has a
      poor prognosis and oncologists often choose a whole body therapy without the benefit of
      prospective efficacy data. Very little prospective investigation into the efficacy of
      specific chemotherapy regimens as a function of line of therapy has been performed in this
      patient population. Nab-paclitaxel is type of chemotherapy that has demonstrated activity in
      other types of cancer such as lung and head and neck cancers. The primary objective of this
      study is to determine the response rate (percentage of subjects with tumor shrinkage) to
      nab-paclitaxel treatment in subjects with cutaneous SCC who have not received cytotoxic
      chemotherapy in the unresectable or the metastatic settings.. Secondary objectives are the
      progression free survival (time until tumor starts to grow), safety, assessment of the
      percentage of subjects whose tumor expresses a protein called SPARC, and correlating the
      expression of SPARC with response to treatment. To determine if the tumor expresses SPARC
      part of a prior standard biopsy such as that performed to establish the diagnosis of SCC will
      be used. SPARC is a protein that is overexpressed in a range of different cancer types and
      may alter the environment around the tumor possibly in a way that may make the SCC more
      responsive to treatment with nab-paclitaxel.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed unresectable locoregional or distantly metastatic squamous
             cell carcinoma arising from a cutaneous surface, lip, or ear. Basosquamous histology
             is eligible.

          -  ECOG PS 0 or 1

          -  Life expectancy of more than 4 months

          -  Adequate renal, hepatic, and bone marrow function:

          -  Patients must have adequate liver function: AST and ALT < 2.5 X upper limit of normal,
             alkaline phosphatase < 2.5 X upper limit of normal, unless bone metastasis is present
             in the absence of liver metastasis, Bilirubin < 1.5 mg/dL

          -  Patients must have adequate bone marrow function: Platelets >100,000 cells/mm3,
             Hemoglobin > 9.0g/dL, WBC > 3,000 cells/mm3, and ANC > 1,500 cells/mm3

          -  Patients must have adequate renal function: creatinine <1.5 mg/dL

          -  Age > 18 years old

          -  Women of childbearing potential and sexually active males must agree to use effective
             contraception during treatment and for three months after completing treatment

          -  Negative serum or urine B-hCG pregnancy test at screening for patients of childbearing
             potential

          -  No previous or concurrent malignancy except inactive nonmelanoma skin cancer, in situ
             carcinoma of the cervix, treated grade 1 papillary bladder cancer, localized prostate
             cancer detected via biopsy only and being treated with "watchful waiting", or other
             cancers where the patient has no evidence of recurrence for more than 5 years

          -  Must be at least 28 days since surgical procedure and/or radiation therapy and at
             least 4 weeks since last treatment with targeted therapies such as cetuximab or
             immunotherapy.

          -  No significant inter-current illness such as serious infection requiring intravenous
             antibiotics.

          -  Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE v4.0)

          -  Ability to provide informed consent

        Exclusion Criteria:

          -  Prior systemic cytotoxic chemotherapy for unresectable SCC. Prior adjuvant or
             neoadjuvant cytotoxic chemotherapy provided not within prior 28 days is allowed. Prior
             systemic therapies with a targeted agent (cetuximab) or immunotherapy in the setting
             of unresectable SCC (is allowed).

          -  Prior taxane based chemotherapy

          -  The presence of any CNS tumor that has not been stable for at least 3 months off of
             corticosteroids and confirmed by imaging.

          -  Prior major organ transplant or autoimmune disease requiring chronic immunosuppression

          -  Psychiatric illness or social situation that would preclude compliance.

          -  Active or chronic infection with HIV, hepatitis B or hepatitis C. Formal testing
             should be performed if clinical suspicion.

          -  Patients with New York Heart Association class II, III, or IV disease or arrhythmia
             requiring treatment (rate controlled Atrial fibrillation is allowed)

          -  Lack of measurable disease on imaging studies as defined by RECIST 1.

          -  Any condition that in the opinion of the treating physician is likely to prevent the
             patient from complying with any aspect of the protocol or that may put the patient at
             unacceptable risk

          -  Known allergy to treatment medication