Palmar-Plantar Erythrodysesthesia Syndrome (PPES) MedDRA version: 14.1 Level: LLT Classification code 10054524 Term: Palmar-plantar erythrodysesthesia syndrome System Organ Class: 100000004858
Conditions
Interventions
Product Name: ATH008 cream 3%
Product Code: ATH008 cream
Pharmaceutical Form: Cream
INN or Proposed INN: Allopurinol
CAS Number: 315-30-0
Concentration unit: % percent
Concentration type: equal
Concen
Sponsors
Advancell Advanced In Vitro Cell Technologies, S.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Have signed Informed Consent. • Are under capecitabine therapy for treatment of colon or breast cancer at a regimen of 2 weeks on and 1 week off (14+7) and a daily doses between 2000 and 2500 mg/m2. • Diagnosis of PPES grade 1 in any hand or foot according to the NCI CTCAE v4.03 definition. • Are able to apply topical medication or provide for another person to apply it. • Have a life expectancy longer than 3 months. • In Part I, subjects still have to undergo at least 1 planned cycle with capecitabine therapy. • In Part II, subjects still have to undergo at least 2 planned cycles with capecitabine therapy Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Are younger than 18 years. • Have neurologic symptoms greater than grade 1, which under the criteria of the clinician could interfere with PPES diagnosis or study treatment (e.g. hands or feet neuropathy). • Diagnosis of PPES grade 1 in any hand or foot according to the NCI CTCAE v4.03 definition (Appendix 20.1) for more than 2 cycles previously to inclusion in this clinical study. • Have any dermatologic condition that in the opinion of the investigator may affect hands or feet or may complicate evaluation during study treatment (e.g. neurodermatitis, psoriasis, etc). • Use of other chemotherapies for the treatment of cancer except trastuzumab (Herceptin ®) or bevacizumab (Avastin ®) • Have onycholysis with a non-stable grade 1 or onycholysis greater than grade 1 (nail loss, NCI CTCAE v4.03 criteria) which in the assessment of the clinician could interfere with PPES diagnosis or treatment. • Need to use other emollient creams or other topical treatments in hands and/or feet during the study. • Are receiving radiotherapy. • Are actively treated with systemic allopurinol (oral or parenteral) for the treatment of gout, or any other indication. • Have developed a severe reaction to allopurinol in the past (e.g. Lyell syndrome). • Known allergy to allopurinol or any of the excipients of the product. • Previous contraindication to treatment with capecitabine. • Have received topical corticosteroids in hands and/ or feet 7 days prior to planned inclusion in the study. • Are participating in any other investigational studies for the treatment of PPES. • Have participated in any other investigational studies for the treatment of PPES, or received an experimental therapeutic procedure, considered to potentially interfere with the study in the 4 weeks preceding Day 1. • Have a serious medical or psychiatric condition that could, in the investigator’s opinion, potentially interfere with their study treatment or participation in the study. • Pregnant women, women in child bearing age not using contraceptives or men not using contraceptives. Methods of contraception which have a failure rate (Pearl index) of less than 1% per year are regarded as highly effective. • Are participating in other clinical trials. • Haematological limits indicating that capecitabine (Xeloda®) cannot be administered due to safety reasons, based on the PI review before each cycle of chemotherapy. • Total bilirubin > 3 upper normal value. • Serum creatinine level > 2 upper normal value.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part I – Safety evaluation •To demonstrate the safety of ATH008 cream in patients presenting PPES secondary to capecitabine therapy. • To determine the plasmatic levels of the active ingredient, allopurinol, and its metabolite, oxypurinol, when given topically. • To select the dose for Part II of this study. Part II – Safety and Primary Efficacy evaluation • To demonstrate the safety of ATH008 cream in patients presenting PPES secondary to capecitabine therapy. • To demonstrate the efficacy of ATH008 cream in reducing the number of subjects presenting PPES grade 2/3 secondary to capecitabine therapy. ;Timepoint(s) of evaluation of this end point: Primary timepoint for Part II: V0, V1 (1-5th day of capecitabine cycle), V2 (D21 ±3), V3 (D42 ±3), V4 (D63 ±3) and V5 (1st day of next capecitabine cycle);Secondary Objective: Part I • To determine the grade of PPES at Day 1 and Day 21 of ATH008 cream treatment. Part II – Secondary Efficacy evaluation • To determine the plasmatic levels of the active ingredient, allopurinol, and its metabolite, oxypurinol, when given topically. • To demonstrate the efficacy of ATH008 cream in improving the quality of life of patients presenting PPES. • To demonstrate the efficacy of ATH008 cream in improving the signs and symptoms of PPES. ;Primary end point(s): Safety variables Part I and II Adverse events and serious adverse events (incidence, causality, and severity) related to treatment with ATH008 cream. Pharmacokinetic variables Part I • Plasmatic allopurinol levels. • Plasmatic oxypurinol levels. Part II • Plasmatic allopurinol levels. • Plasmatic oxypurinol levels. Primary efficacy variable Part I None. Part II Percentage of subjects that develop PPES grade 2 or 3 according to the NCI CTCAE v4.03 criteria | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): o Efficacy evaluation: ? To demonstrate the efficacy of ATH008 cream in improving the quality of life of patients presenting PPES. ? To demonstrate the efficacy of ATH008 cream in improving the signs and symptoms of PPES. o Apart from primary and secondary end-point, we also have Exploratory objectives: ? To describe the accumulated dose intensity of capecitabine before and during treatment in order to find any possible correlation between the efficacy of the product and the accumulated dose intensity before development of PPES grade 2 or 3. ;Timepoint(s) of evaluation of this end point: o Secondary timepoint for Part II: V0, V1 (1-5th day of capecitabine cycle), V2 (D21 ±3), V3 (D42 ±3), V4 (D63 ±3) and V5 (1st day of next capecitabine cycle) | — |
Countries
Belgium, Germany, Italy, Spain
Contacts
Public ContactMarta Rayo Lunar
Advancell Advanced In Vitro Cell Technologies, S.A
Outcome results
None listed