E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Palmar-Plantar Erythrodysesthesia Syndrome (PPES) |
|
E.1.1.1 | Medical condition in easily understood language |
Hand-foot syndrom caused by chemotherapy |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054524 |
E.1.2 | Term | Palmar-plantar erythrodysesthesia syndrome |
E.1.2 | System Organ Class | 100000004858 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
|
|
E.2.2 | Secondary objectives of the trial |
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.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
|
|
E.4 | Principal 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.
|
|
E.5 End points |
E.5.1 | 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
|
|
E.5.1.1 | 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) |
|
E.5.2 | 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.
|
|
E.5.2.1 | 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) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
This is provided in the protocol |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |