Talimogene Laherparepvec and Panitumumab for the Treatment of Locally Advanced or Metastatic Squamous Cell Carcinoma of the Skin
Condition: Locally Advanced Skin Squamous Cell Carcinoma; Metastatic Skin Squamous Cell Carcinoma; Recurrent Skin Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell
Intervention: Panitumumab; Talimogene Laherparepvec
Intervention description: Given IV; Given IM
Intervention MeSH terms: Antineoplastic Agents, Immunological; Panitumumab; Talimogene laherparepvec; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase I trial studies the side effects and how well talimogene laherparepvec and
      panitumumab work in treating patients with squamous cell carcinoma of the skin that has
      spread to nearby tissues or lymph nodes (locally advanced) or other places in the body
      (metastatic). Talimogene laherparepvec is a type of vaccine made from a gene-modified virus
      that may help the body build an effective immune response to kill tumor cells. Immunotherapy
      with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the
      cancer, and may interfere with the ability of tumor cells to grow and spread. Giving
      talimogene laherparepvec and panitumumab may work better in treating patients with squamous
      cell carcinoma of the skin compared to panitumumab alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed squamous cell carcinoma of the skin (SCCS) that is a) locally
             advanced or metastatic for which curative surgery or radiation would be difficult or
             impossible, or b) recurrent after initial surgery, chemotherapy, or radiation therapy,
             or c) considered to have aggressive features including the following: tumors 2 cm or
             more, tumors invading deep tissues such as muscle, cartilage or bone; tumors showing
             perineural invasion, and/or tumors metastatic to loco-regional lymph nodes. Patients
             may have had prior surgical interventions or been treated with investigational agents
             with residual or recurrent disease

          -  Tumor suitable for direct or ultrasound-guided injection defined as at least one
             cutaneous, subcutaneous, or nodal lesion, or aggregate of lesions, >= 10 mm in
             diameter

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  No prior treatment with panitumumab or talimogene laherparepvec for advanced disease

          -  Prior surgery or radiation is allowed if there is documented progression in the
             radiated/resected area or elsewhere by Response Evaluation Criteria in Solid Tumors
             (RECIST) criteria version (v) 1.1

          -  Measurable disease by RECIST criteria v 1.1

          -  Patients with a history of hematologic or solid organ transplant will be considered if
             they do not require high dose steroids or high dose immunosupressants for disease
             control or control of transplant rejection, and have adequate hematologic, renal, and
             hepatic function as specified below. Current medications must be reviewed with
             transplant pharmacy team to exclude potentially serious interactions and case
             discussed with the study principal investigator (PI)

          -  Second primary malignancy only if treatment would interfere with the patient?s
             participation in this trial in the opinion of the treating physician. Clear exceptions
             are 1) patient had a second primary malignancy but has been treated and disease free
             for at least 3 years, 2) in situ carcinoma (e.g., in situ carcinoma of the cervix)
             and, 3) additional skin cancers that have been definitively treated by surgery and/or
             radiation. Patients with chronic lymphocytic leukemia will be allowed if their blood
             counts are within acceptable hematologic parameters and if they are not currently
             requiring cytotoxic or biologic anticancer treatment (supportive treatment such as
             intravenous immunoglobulin [IVIG] is permitted)

          -  Patients with autoimmune disorders will be considered if they do not require high dose
             steroids or other immunosuppressants for disease control. Prednisone in daily doses up
             to 10 mg and inhaled steroids are acceptable

          -  Absolute neutrophil count (ANC) >= 1500/uL

          -  Platelet count >= 100,000/mm^2

          -  Hemoglobin >= 9 g/dL

          -  Total bilirubin < 1.5 x institutional upper limit of normal (ULN); if patient has
             conditions of congenital hyperbilirubinemia, then patient must have isolated
             hyperbilirubinemia (e.g., no other liver function test abnormalities) with maximum
             bilirubin < 2 x institutional ULN

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x
             institutional ULN in absence of liver metastases; =< 5 x ULN in presence of liver
             metastases

          -  Alkaline phosphatase < 2.5 x institutional ULN

          -  Creatinine < 1.5 x institutional ULN or calculated creatinine clearance >= 60 mL/min
             as estimated using the Cockcroft-Gault formula

        Exclusion Criteria:

          -  Pregnant women. Women of childbearing age must be willing to undergo a pregnancy test
             prior to therapy and to use adequate contraception (e.g., hormonal or barrier method
             of contraception or abstinence) for the duration of the study and 6 months thereafter.
             Should a woman become pregnant or suspect she is pregnant while participating in this
             study, she should inform her treating physician immediately. Menopausal status will be
             defined as one or more of successful hysterectomy, bilateral tubal ligation or
             bilateral oophorectomy, amenorrhea >= 12 consecutive months without another cause, or
             a documented serum follicle stimulating hormone (FSH) >= 35 mIU/mL

          -  Tumor not suitable for direct or ultrasound-guided injection

          -  Prior treatment with talimogene laherparepvec for advanced disease

          -  Patients with active, uncontrolled infections including active herpetic infections or
             chronic herpetic infections requiring anti-viral therapy (e.g., acyclovir)

          -  Patients without adequate organ function as documented above

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to panitumumab, talimogene laherparepvec or other agents used in the study

          -  History of interstitial pneumonitis, pulmonary fibrosis, or evidence of interstitial
             pneumonitis