Topical Sildenafil as Pre-Treatment for Hand-Foot Skin Reaction

NCT03229512 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: JNC052716
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

Skin toxicities are a major complication to cancer therapies. They can be painful and limit the amount of drug that can be received by cancer patients, preventing the patients from receiving optimal doses of drug. One such cutaneous toxicity, hand-foot skin reaction (HFSR), is caused by next generation targeted agents that are in routine use for the treatment of kidney and liver cancer. HFSR is characterized by swelling, redness, and pain of the palms and soles, in addition to the development of painful or thickened callus-like plaques with fissures in areas of friction and pressure. The investigators have identified a topical skin-directed therapy, 1% topical sildenafil cream, that the investigators believe will be useful in preventing and ameliorating this painful, skin side effect associated with the targeted agents sorafenib and sunitinib. This project proposal aims to conduct an open-label pilot study to assess whether pre-medication with this cream can be an effective way of preventing or decreasing the severity of hand-foot skin reaction, improving their quality of life on therapy and enabling the patients to receive optimal amounts of their anti-cancer drug.

Conditions

Hand Foot Skin Reaction

Keywords

Hand Foot Skin Reaction; Sildenafil

Outcome Measures

Primary Outcomes (1)

• Evidence of hand-foot skin reaction

  The primary outcome measure is the onset and calculated incidence of any grade of hand-foot skin reaction during the 12-week study period.

  Within 12 weeks of start of study

Secondary Outcomes (1)

• Adverse events due to 1% sildenafil cream

  Within 12 weeks of start of study

Study Arms (1)

Intervention

EXPERIMENTAL

Topical 1% Sildenafil Cream

Drug: Sildenafil

Interventions

Sildenafil DRUG

Topical 1% Sildenafil Cream

Also known as: Sildenafil citrate, Viagra

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a clinical diagnosis of cancer that are within ± 3 days of initiating treatment with sorafenib or sunitinib. Patients treated with a combination regimen that includes sorafenib or sunitinib are eligible.
• Patients must be age ≥ 18 years.
• Patients must exhibit an ECOG performance status of 0 to 2.
• Females of child-bearing potential (FOCBP) and males must agree to use adequate contraception (e.g., hormonal contraceptives such as birth control pills, patch, intrauterine device; barrier contraception such as male/female condoms, diaphragm; male partner with vasectomy; abstinence) prior to study entry, for the duration of study participation, and for 30 days following completion of therapy. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy or has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months).
• FOCBP must have a negative urine or serum pregnancy test within 7 days prior to registration on study.
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration in the study.

You may not qualify if:

• Patients with a prior diagnosis of hand-foot skin reaction are not eligible.
• Patients who have had other chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are not eligible.
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to sildenafil or phosphodiesterase-5 (PDE5) inhibitors such as vardenafil (Levitra) and tadalafil (Cialis) are not eligible.
• Patients may not be receiving any other investigational agents. Note: it is acceptable to be on combination therapy including either sorafenib and/or sunitinib.
• Patients must not be using topical steroids (e.g., hydrocortisone). Topical over-the-counter antibiotics (e.g., Neosporin) and skin protectants (e.g., Vaseline, Aquaphor) for local skin fissures on hands and feet are allowed. Patients are allowed to use topical medications on other body parts, besides the hands and feet, but must use qtips or gloves for application.
• Patients taking nitrates (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate) and/or alpha blockers (e.g., tamsulosin, prazosin, afluzosin, silodosin) are not eligible.
• Patients taking Viagra must have a 1 day washout period prior to treatment. Note: patients must agree to discontinue Viagra while on study treatment.
• Female patients who are pregnant or nursing are not eligible.
• Patients must not have any condition or situation which, in the investigator's opinion, puts the patient at significant risk, could confound the study results, or may interfere significantly with the patient's participation in the study.
• Patients who are unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function are not eligible.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (2)

Department of Dermatology, Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Related Publications (3)

• Choi JN. Chemotherapy-induced iatrogenic injury of skin: new drugs and new concepts. Clin Dermatol. 2011 Nov-Dec;29(6):587-601. doi: 10.1016/j.clindermatol.2011.08.032.

  PMID: 22014981 BACKGROUND

• Lacouture ME, Wu S, Robert C, Atkins MB, Kong HH, Guitart J, Garbe C, Hauschild A, Puzanov I, Alexandrescu DT, Anderson RT, Wood L, Dutcher JP. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008 Sep;13(9):1001-11. doi: 10.1634/theoncologist.2008-0131. Epub 2008 Sep 8.

  PMID: 18779536 BACKGROUND

• Meadows KL, Rushing C, Honeycutt W, Latta K, Howard L, Arrowood CA, Niedzwiecki D, Hurwitz HI. Treatment of palmar-plantar erythrodysesthesia (PPE) with topical sildenafil: a pilot study. Support Care Cancer. 2015 May;23(5):1311-9. doi: 10.1007/s00520-014-2465-z. Epub 2014 Oct 24.

  PMID: 25341548 BACKGROUND

MeSH Terms

Interventions

Sildenafil Citrate

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jennifer N Choi, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Division of Oncodermatology

Study Record Dates

• First Submitted: July 21, 2017
• First Posted: July 25, 2017
• Study Start: April 11, 2017
• Primary Completion: June 4, 2020
• Study Completion: June 4, 2020
• Last Updated: November 1, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)