Treatment of Palmar Plantar Erythrodysesthesia (PPE) With Topical Sildenafil

NCT01219023 | Completed Phase 1

• 1 other identifier: Pro00021480
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysethesia (PPE), occurs in a 25%-50% of patients treated with several commonly used anti-cancer drugs including capecitabine and sunitinib. These drugs are known to improve survival in many cancers, including cancers of the colon, stomach, liver, breast, kidney, and GI stromal tumors (GIST). Worldwide, over 400,000 patients per year are treated with one of these agents. HFS involves skin changes, such as swelling, peeling, and blistering of the palms and soles, which is often painful and debilitating. As a result, HFS-related symptoms can frequently lead to dose reduction and/or discontinuation of otherwise effective anti-cancer treatment. There is no treatment for HFS other than dose reduction or stopping treatment. This proposal could quickly lead to treatments to prevent and/or treat HFS and help patients avoid debilitating side effects while continuing otherwise effective treatments for their cancer.

Conditions

Hand Foot Syndrome; Palmar Plantar Erythrodysesthesia

Keywords

Hand foot syndrome; Palmar Plantar Erythrodysesthesia; chemotherapy; Sunitinib; Capecitebine; Sildenafil

Outcome Measures

Primary Outcomes (3)

• Grade of hand foot syndrome over time as measured by NCI CTC version 4.0 PPE syndrome criteria

  Grading of PPE by NCI CTC criteria occurs every 2 weeks for subjects in the sunitinib arm for 1st 8 weeks (and as clinically indicated). Grading of PPE by NCI CTC criteria occurs every 3 weeks for subjects in the capeccitabine arm for the 1st 9 weeks (and as clinically indicated)

  Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)

• Assessment of patient reported pain, at rest and when making a fist, using a 1-10 score.

  Assessment of patient reported pain, at rest and when making a fist, using a 1-10 score, is collected on a diary card that subjects fill out twice daily.

  twice daily

• Assessment of severity of erythema and desquamation or blistering as measured on 0-4 score from photographs.

  Assessment of severity of erythema and desquamation or blistering as measured on 0-4 score from photographs of hands and/or feet taken every two weeks (for subjects in sunitinib arm) or every 3 weeks (for subjects in capecitabine arm).

  Every 2 weeks (sunitinib arm); Every 3 weeks (capecitabine arm)

Interventions

sildenafil citrate DRUG

Subjects will be given 2 types of topical creams, one containing 1% sildenafil and one containing placebo control. Subjects will be randomized to apply sildenafil cream to either the right or left hand/foot; placebo cream will be applied to the opposite hand/foot. The cream will be supplied to subjects with proper labeling to indicate right and left application assignment. Cream will be applied to each affected hand/foot two times per day.

Also known as: Viagra

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet the following criteria to be eligible for the study:
• Receiving capecitabine or sunitinib as part of routine standard care.
• CTCAE version 4.0, grade 1-3 PPE.
• Adults age ≥ 18
• Karnofsky (KPS) performance status of ≥70%
• Adequate organ and marrow function as defined below:
• \- ANC \> 1000/mL
• \- Platelets \> 75,000/mL
• \- Total bilirubin \< 1.5 x UNL
• \- AST(SGOT)/ALT(SGPT) \< 5 x UNL
• \- Creatinine Cr Cl est \> 40 mL/min (by Cockcroft-Gault)
• Not pregnant or lactating.
• Use of adequate birth control with female partners of male subjects agreeing to use a medically acceptable form of birth control: (1) surgical sterilization, (2) approved hormonal contraceptives (such as birth control pills or Depo-Provera), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, (4) an intrauterine device (IUD) or (5) post menopausal. Abstinence is not considered acceptable birth control. Postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Subjects meeting any of the following criteria are ineligible for study entry:
• Currently participating in a clinical trial.
• History of hypersensitivity or intolerance to sildenafil or other related products tadalafil (Cialis™), vardenafil (Levitra™) or poloxamer vehicle.
• Currently taking oral sildenafil or other related products tadalafil (Cialis™), vardenafil (Levitra™).
• Currently taking other treatment for PPE other than standard emollients.
• Using organic nitrates, either regularly and/or intermittently, in any form.
• History of myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.
• Resting hypotension (BP \<90/50 mmHg) or hypertension (BP \>170/110 mmHg). Those subjects on alpha-blocker or anti-hypertensive therapy must be hemodynamically stable for at least two weeks before day 1 of study drug.
• Cardiac failure or coronary artery disease causing unstable angina.
• Known retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).
• Concomitant use of strong cytochrome P450 3A4 inducers or inhibitors (Ex: ketoconazole, itraconazole, erythromycin, saquinavir).
• Other acute or chronic inflammatory conditions or infections of the hands or feet that would complicate safety, application of topical creams, or study endpoints.
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
• Pregnant or breast-feeding and/or lactating.
• Inability or unwillingness to comply with protocol.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Hand-Foot Syndrome

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Drug Eruptions; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

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

• Herbert Hurwitz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2010
• First Posted: October 13, 2010
• Study Start: June 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: October 30, 2012

Record last verified: 2012-10

Locations

US (1)