Intralesional 5-Fluorouracil (5FU), Topical Calcipotriene Treatment for SCC

Inclusion Criteria: * Biopsy-confirmed SCC more than 1.0 cm and less than 2.0 cm in diameter in the lower extremities, defined as the knees and below. * Subjects must have an expected survival of greater than or equal to12 months. * Subjects must not be on any other investigational device/drug treatment. * Subjects must to be willing to adhere to the instructions of the Investigator and his research team and sign an Informed Consent Form prior to entry into the study. * Patient is ≥ 18 years of age on day of signing informed consent. * Patient must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. * Female patient of childbearing potential has a negative urine or serum pregnancy test within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patient to be eligible. * Female patients enrolled in the study, who are not free from menses for \> 2 years, post hysterectomy/oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy, or to abstain from heterosexual activity throughout the study, starting with the first dose of study drug at visit 1 through 120 days after the last dose of study drug. Approved contraceptive methods include for example: intra-uterine device, diaphragm with spermicide, cervical cap with spermicide, male condoms, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception. Male patients must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug. Exclusion Criteria: * Patients with any evidence of nodal (Nx) and/or metastatic disease including distant subcutaneous and/or lymph node metastases. * Patients with primary non-cutaneous SCC - such as nasopharyngeal SCC. * Patient with history of receiving organ transplantation. * Patients with history of iatrogenic systemic immunosuppression. * Patients with a history of skin or other disorder(s),that in the opinion of the investigator, requires topical application of steroids and/or other creams/ointments. * Patients with evidence of active infection - active and/or untreated hepatitis B/C, HIV, etc - requiring systemic therapy. * Patients with a known history of autoimmune disease. * Patients with the following cardiac co-morbidities including: * Baseline known prolongation of QT/QTc interval (QTc interval \>500 msec). * Heart failure either on clinical examination (manifestations include ascites, cardiomegaly, dyspnea, edema, gallop rhythm, hepatomegaly, oliguria, pleural effusion, pulmonary edema, tachycardia) or based on known decreased left ventricular ejection fraction (LV EF) \<50%. * Patients who have had chemotherapy, radioactive or biological cancer therapy within four weeks prior to the first dose of study drug, or who has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the adverse effects (AEs) due to cancer therapeutics administered more than four weeks earlier. Subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study. * If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. * Patients currently participating or who have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study drug. * Patients expected to require any other form of systemic or localized antineoplastic therapy while on study. * Patients with a known history of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the patient has undergone potentially curative therapy with no evidence of that disease for five years. ° The time requirement also does not apply to patients who underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cancers including cervical cancer, breast cancer, melanoma, or other in situ cancers. * Patients who have previously had a severe hypersensitivity reaction to 5-fluorouracil or imiquimod. * Serious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, autoimmune diseases, severe obstructive or restrictive pulmonary diseases, active systemic infections, and inflammatory bowel disorders. * Patients with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or are not in the best interest of the patient to participate, in the opinion of the treating Investigator. * Patients who are, at the time of signing informed consent, regularly using illicit drugs or are recently (within the last year) abusing illicit substances (including alcohol). * Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.