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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03370406
Recruitment Status : Recruiting
First Posted : December 12, 2017
Last Update Posted : September 14, 2021
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Melissa Pugliano-Mauro, University of Pittsburgh

Brief Summary:
This clinical trial proposes to evaluate a relatively unexplored approach to treatment of squamous cell carcinoma (SCC) on the lower extremities. The strategy is to directly and specifically deliver drug to the tumor. For the proposed phase I clinical trial, the investigators will perform intralesional injections of a well characterized, potent chemotherapeutic agent 5-fluorouracil (5FU) with and without a topical application of 5% imiquimod to kill topically accessible SCC cells. The goal of the study is to evaluate the safety profile and tolerability of intralesional-5FU with and without a concomitant topical imiquimod and measure the clinical objective response rate (ORR) in treated lesions compared to untreated lesions 3 weeks after treatment.

Condition or disease Intervention/treatment Phase
Carcinoma, Squamous Cell Drug: 5-fluorouracil Drug: Imiquimod 5% cream Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 10 participants will serve as a control group, and will receive neither 5FU injection nor topical imiquimod. 10 participants will receive one 1ml intralesional injection of 50mg/ml 5FU aqueous injectable solution every week for 3 weeks. 10 participants will receive intralesional 5FU as in the previous group, additionally they will also receive concomitant three-times-weekly topical application of 5% imiquimod to the same lesion. At the end of week two, a 2mm punch biopsy of the lesion will be obtained for mid-point analysis, and will be stored for tissue banking. A week after the last injection (week 4), the lesion will be surgical resected in all participants including the control group, to render the participants disease free. Resection is the current standard of care. A portion of the resected tumor and skin will also be stored for tissue banking, for future study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, Dual Arm, Open-Label, Trial of Intralesional 5-Fluorouracil (5FU) and Intralesional 5FU Combined With Topical Imiquimod in Patients With Squamous Cell Carcinoma (SCC) of the Lower Extremities
Actual Study Start Date : August 3, 2018
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
No Intervention: Control Group
Control group will receive neither 5-fluorouracil (5FU) injection nor topical Imiquimod 5% cream. This group will receive standard of care only. Lesion will be surgical resected on day 21 of study.
Experimental: 5FU Group
5-fluorouracil (5FU) Group participants will receive a 1ml intralesional injection of 5FU 50mg/ml aqueous injectable solution. One injection will be administered weekly for 3 weeks. Injections will occur on d0, d7, and d14. Standard of care will be administered on d21 of study and lesion will be surgical resected.
Drug: 5-fluorouracil
Intralesional injections of 50mg/ml over a 3 week period.
Other Names:
  • Adrucil
  • Tolak
  • Efudex
  • Carac
  • Fluoroplex
  • PremierPro Rx Fluorouracil
  • Fluorouracil Novaplus
  • 5FU

Experimental: 5FU + Imiquimod 5% Group
5-fluorouracil (5FU) + Imiquimod 5% cream Group participants will receive intralesional 5FU as in the previous group, additionally participants will also receive three-times-weekly topical application of 5% imiquimod to the same lesion. Standard of care will be administered on d21 of study and lesion will be surgical resected.
Drug: 5-fluorouracil
Intralesional injections of 50mg/ml over a 3 week period.
Other Names:
  • Adrucil
  • Tolak
  • Efudex
  • Carac
  • Fluoroplex
  • PremierPro Rx Fluorouracil
  • Fluorouracil Novaplus
  • 5FU

Drug: Imiquimod 5% cream
Topical application of 5% cream over a 3 week period.
Other Names:
  • Aldara
  • Zyclara

Primary Outcome Measures :
  1. Determine number of subjects experiencing Dose Limiting Toxicity (DLT) higher than grade 2, as defined by CTCAE v. 4.0 [ Time Frame: 21 days ]

    To assess Dose Limiting Toxicities (DLT) of intralesional-5FU and intralesional 5FU combined with topical imiquimod in subjects after 3 weeks of treatment.

    Dose Limiting Toxicities (DLT) are defined as:

    Higher-than grade 2 hematologic or non-hematologic toxicity that is definitely, probably, or possibly related to intralesional 5FU administration and/or topical imiquimod application. The NCI common terminology criteria for adverse events (CTCAE) version 4.0 will be used.

    Based on the results of the previous studies on treating SCCs with 5FU injection or topical imiquimod, significant toxicities are not expected. Adverse reactions were limited to local site reactions such as treatment site pain, induration, erythema, edema.

    If a patient has a DLT, doses will be delayed if any Grade >2 toxicities are not resolved to Grade 1 by the time of the next dose.

Secondary Outcome Measures :
  1. Asses clinical objective response rate [ Time Frame: 21 days ]
    Measure reduction in tumor burden to assess clinical objective response rate (ORR) in treated lesions. Response will be evaluated using modified Composite Assessment of Index Lesion Severity (CAILS) criteria by bi-dimensional measurement.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03370406

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Contact: Melissa Pugliano-Mauro, MD (412) 996-6428
Contact: Jeff Plowey, MS (412) 724-7375

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United States, Pennsylvania
St. Margaret Hospital Dermatology Recruiting
Pittsburgh, Pennsylvania, United States, 15238
Contact: Melissa Pugliano-Mauro, MD    412-784-7350   
Contact: Jeff Plowey, MS, MBA    412-784-7350   
Principal Investigator: Melissa Pugliano-Mauro, MD         
Sub-Investigator: Kristin Bibee, MD, PhD         
Sub-Investigator: Erin Skaros, PA-C         
Sub-Investigator: Changhyun Kim, MD         
Sub-Investigator: Jeff Plowey, MS, MBA         
Sponsors and Collaborators
Melissa Pugliano-Mauro
National Cancer Institute (NCI)
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Principal Investigator: Melissa Pugliano-Mauro, MD University of Pittsburgh
  Study Documents (Full-Text)

Documents provided by Melissa Pugliano-Mauro, University of Pittsburgh:
Informed Consent Form  [PDF] July 25, 2018


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Responsible Party: Melissa Pugliano-Mauro, Assistant Professor of Dermatology, University of Pittsburgh Identifier: NCT03370406    
Other Study ID Numbers: PRO17090183
5P50CA121973-10 ( U.S. NIH Grant/Contract )
First Posted: December 12, 2017    Key Record Dates
Last Update Posted: September 14, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendicies)
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Immediately following publication. No end date.
Access Criteria:

Investigators whose proposed use of the data has been approved by an independent review committee (learned intermediary) identified for this purpose.

To achieve aims in the approved proposal.

Proposals may be submitted up to 36 months following article publication. Proposals should be directed to To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years through RedCap.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Melissa Pugliano-Mauro, University of Pittsburgh:
Squamous Cell
Lower Extremities
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Interferon Inducers