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

NCT03370406 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY190902295P50CA121973-10
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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 0.005% calcipotriene cream 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 calcipotriene and measure the clinical objective response rate (ORR) in treated lesions compared to untreated lesions 3 weeks after treatment.

Conditions

Carcinoma, Squamous Cell

Keywords

Squamous Cell; Carcinoma; Lower Extremities; 5-Fluorouracil; Imiquimod

Outcome Measures

Primary Outcomes (1)

• Determine number of subjects experiencing Dose Limiting Toxicity (DLT) higher than grade 2, as defined by CTCAE v. 4.0

  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.

  84 days

Secondary Outcomes (1)

• Asses clinical objective response rate

  84 days

Study Arms (3)

Control Group

NO INTERVENTION

Control group will receive neither 5-fluorouracil (5FU) injection nor topical 0.005% calcipotriene cream. This group will receive standard of care only. Lesion will be surgical resected on day 84 of study.

5FU Group

EXPERIMENTAL

5-fluorouracil (5FU) Group participants will receive a 1ml intralesional injection of 5FU 50mg/ml aqueous injectable solution. One injection will be administered once monthly for 3 month. Injections will occur on d0, d28, and d56. Standard of care will be administered on d84 of study and lesion will be surgical resected.

Drug: 5-fluorouracil

5FU + 0.005% Calcipotriene cream Group

EXPERIMENTAL

5-fluorouracil (5FU) + 0.005% calcipotriene cream Group participants will receive intralesional 5FU as in the previous group, additionally participants will also receive two (2) times daily for four (4) days one (1) day after each of three (3) 5FU injections topical application of 0.005% calcipotriene cream to the same lesion. Standard of care will be administered on d84 of study and lesion will be surgical resected.

Drug: 5-fluorouracil; Drug: Calcipotriene

Interventions

5-fluorouracil DRUG

Intralesional injections of 50mg/ml over a 3 week period.

Also known as: Adrucil, Tolak, Efudex, Carac, Fluoroplex, PremierPro Rx Fluorouracil, Fluorouracil Novaplus, 5FU

5FU + 0.005% Calcipotriene cream Group; 5FU Group

Calcipotriene DRUG

Topical application of .005% cream two (2) times daily for four (4) days one (1) day after each of three (3) 5FU injections..

Also known as: Dovonex, Calcitrene, Sorilux, Calsodore, Kalosar

5FU + 0.005% Calcipotriene cream Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Melissa Pugliano-Mauro: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

St. Margaret Hospital Dermatology

Pittsburgh, Pennsylvania, 15238, United States

RECRUITING

Related Publications (13)

• Rosenberg AR, Tabacchi M, Ngo KH, Wallendorf M, Rosman IS, Cornelius LA, Demehri S. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019 Mar 21;4(6):e125476. doi: 10.1172/jci.insight.125476. eCollection 2019 Mar 21.

  PMID: 30895944 BACKGROUND

• Cunningham TJ, Tabacchi M, Eliane JP, Tuchayi SM, Manivasagam S, Mirzaalian H, Turkoz A, Kopan R, Schaffer A, Saavedra AP, Wallendorf M, Cornelius LA, Demehri S. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017 Jan 3;127(1):106-116. doi: 10.1172/JCI89820. Epub 2016 Nov 21.

  PMID: 27869649 BACKGROUND

• Kim C, Ko CJ, Leffell DJ. Cutaneous squamous cell carcinomas of the lower extremity: a distinct subset of squamous cell carcinomas. J Am Acad Dermatol. 2014 Jan;70(1):70-4. doi: 10.1016/j.jaad.2013.09.026. Epub 2013 Nov 5.

  PMID: 24210370 BACKGROUND

• Solus JF, Murphy GF, Kraft S. Cutaneous Squamous Cell Carcinomas of the Lower Extremities Show Distinct Clinical and Pathologic Features. Int J Surg Pathol. 2016 Feb;24(1):29-36. doi: 10.1177/1066896915599058. Epub 2015 Aug 10.

  PMID: 26261102 BACKGROUND

• Munday WR, Leffell DJ, McNiff JM, Ko CJ. Histopathologic features of multiple cutaneous squamous cell carcinomas of the lower extremity. J Cutan Pathol. 2016 Sep;43(9):759-65. doi: 10.1111/cup.12738. Epub 2016 Jun 14.

  PMID: 27220356 BACKGROUND

• Bangash SJ, Green WH, Dolson DJ, Cognetta AB Jr. Eruptive postoperative squamous cell carcinomas exhibiting a pathergy-like reaction around surgical wound sites. J Am Acad Dermatol. 2009 Nov;61(5):892-7. doi: 10.1016/j.jaad.2009.01.037. Epub 2009 Sep 18.

  PMID: 19766351 BACKGROUND

• Moore AY. Clinical applications for topical 5-fluorouracil in the treatment of dermatological disorders. J Dermatolog Treat. 2009;20(6):328-35. doi: 10.3109/09546630902789326.

  PMID: 19954388 BACKGROUND

• Metterle L, Nelson C, Patel N. Intralesional 5-fluorouracil (FU) as a treatment for nonmelanoma skin cancer (NMSC): A review. J Am Acad Dermatol. 2016 Mar;74(3):552-7. doi: 10.1016/j.jaad.2015.09.040. Epub 2015 Nov 11.

  PMID: 26577512 BACKGROUND

• Kraus S, Miller BH, Swinehart JM, Shavin JS, Georgouras KE, Jenner DA, Griffin E, Korey A, Orenberg EK. Intratumoral chemotherapy with fluorouracil/epinephrine injectable gel: a nonsurgical treatment of cutaneous squamous cell carcinoma. J Am Acad Dermatol. 1998 Mar;38(3):438-42. doi: 10.1016/s0190-9622(98)70502-x.

  PMID: 9520026 BACKGROUND

• Reisinger DM, Cognetta AB Jr, Pynes LT, Paredes AA Jr, Sweeney TJ, Dolson DJ. Treatment of a giant squamous cell carcinoma on the dominant thumb with intralesional 5-fluorouracil. J Am Acad Dermatol. 2011 Jul;65(1):219-21. doi: 10.1016/j.jaad.2009.11.017. No abstract available.

  PMID: 21679825 BACKGROUND

• Morse LG, Kendrick C, Hooper D, Ward H, Parry E. Treatment of squamous cell carcinoma with intralesional 5-Fluorouracil. Dermatol Surg. 2003 Nov;29(11):1150-3; discussion 1153. doi: 10.1046/j.1524-4725.2003.29355.x.

  PMID: 14641346 BACKGROUND

• Love WE, Bernhard JD, Bordeaux JS. Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma: a systematic review. Arch Dermatol. 2009 Dec;145(12):1431-8. doi: 10.1001/archdermatol.2009.291.

  PMID: 20026854 BACKGROUND

• Peris K, Micantonio T, Fargnoli MC, Lozzi GP, Chimenti S. Imiquimod 5% cream in the treatment of Bowen's disease and invasive squamous cell carcinoma. J Am Acad Dermatol. 2006 Aug;55(2):324-7. doi: 10.1016/j.jaad.2006.04.004.

  PMID: 16844522 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Carcinoma

Interventions

Fluorouracil; calcipotriene

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Melissa Pugliano-Mauro, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa Pugliano-Mauro, MD

CONTACT

(412) 996-6428; puglianomauroma@upmc.edu

Jeff Plowey, MS

CONTACT

(412) 724-7375; ploweyjm2@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Dermatology

Model Details: 10 participants will serve as a control group, and will receive neither 5FU injection nor topical calcipotriene. 10 participants will receive one 1ml intralesional injection of 50mg/ml 5FU aqueous injectable solution once a month for 3 months. 10 participants will receive intralesional 5FU as in the previous group, additionally they will also apply 0.005% calcipotriene two (2) times daily for four (4) days one (1) day after each of three (3) 5FU injections to the same lesion. At the end of week eight (8), a 2mm punch biopsy of the lesion will be obtained for mid-point analysis, and will be stored for tissue banking. Four weeka after the last injection (week 12), 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.

Study Record Dates

• First Submitted: December 1, 2017
• First Posted: December 12, 2017
• Study Start: August 3, 2018
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: June 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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 puglianomauroma@upmc.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years through RedCap.

Locations

US (1)