Safety and Efficacy Placebo Controlled Study of ATH008 Cream in PPES Patients Secondary to Capecitabine

This study has been completed.
Sponsor:
Collaborator:
CROMSOURCE
Information provided by (Responsible Party):
Advancell - Advanced In Vitro Cell Technologies, S.A.
ClinicalTrials.gov Identifier:
NCT01316406
First received: March 14, 2011
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

The aim of this study is to evaluate the safety and efficacy of ATH008 cream in patients with Palmar-Plantar Erythrodysesthesia Syndrome (PPES) secondary to capecitabine therapy. In part I, the safety and plasmatic levels of the active ingredient and its metabolite will allow to determine the most appropriate and beneficial dose for the second part of the study. In Part II, the efficacy of ATH008 cream in reducing the number of patients presenting PPES grade 2/3 secondary to capecitabine therapy following a four times daily application will be tested.


Condition Intervention Phase
Palmar-Plantar Erythrodysesthesia Syndrome
Drug: ATH008
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Placebo Controlled, Multicenter Study to Investigate the Safety and Efficacy of ATH008 Cream in Patients With Palmar-Plantar Erythrodysesthesia Syndrome (PPES) Secondary to Capecitabine Therapy.

Resource links provided by NLM:


Further study details as provided by Advancell - Advanced In Vitro Cell Technologies, S.A.:

Primary Outcome Measures:
  • Efficacy of ATH008 cream in reducing the number of subjects presenting PPES grade 2/3 secondary to capecitabine therapy [ Time Frame: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days ] [ Designated as safety issue: No ]
    percentage of subjects that develop PPES grade 2 or 3 according to the NCI CTCAE v4.03 criteria

  • Safety of ATH008 cream in patients presenting PPES secondary to capecitabine therapy [ Time Frame: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days ] [ Designated as safety issue: Yes ]
    adverse events and serious adverse events (incidence, causality, and severity) related to treatment with ATH008 cream

  • Plasmatic levels of ATH008 cream when given topically [ Time Frame: blood sampling at specific timepoints (Pre-dose, Day 1 and Day 21) ] [ Designated as safety issue: Yes ]
    plasmatic levels of the active ingredient and its metabolite when given topically


Secondary Outcome Measures:
  • Efficacy of ATH008 cream in improving the quality of life of patients presenting PPES [ Time Frame: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days ] [ Designated as safety issue: No ]
    quality of life compared to baseline

  • Efficacy of ATH008 cream in improving signs and symptoms of PPES [ Time Frame: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days ] [ Designated as safety issue: No ]
    proportion of subjects that present no PPES signs or symptoms, time to progression and time to improvement of PPES grades,assessment from photographs of erythema, desquamation, existence of blisters, fissures and ulcers; percentage of palms and soles affected by PPES

  • Assessment of patient reported pain [ Time Frame: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days ] [ Designated as safety issue: No ]
    assessment of pain, using a 0-10 score, analysed comparing the values measured during the study treatment period with the baseline pain value

  • Accumulated dose intensity of capecitabine before and during ATH008 cream treatment [ Time Frame: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days ] [ Designated as safety issue: No ]
    accumulated capecitabine dose during study treatment (mg / m2) from the starting of ATH008 cream treatment


Enrollment: 122
Study Start Date: February 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATH008 cream 3%
ATH008 cream 3%
Drug: ATH008
The subject will be incorporated in the study and randomised to ATH008 cream 3% or 8% or ATH008 cream placebo
Other Name: ATH008 cream
Experimental: ATH008 cream 8%
ATH008 cream 8%
Drug: ATH008
The subject will be incorporated in the study and randomised to ATH008 cream 3% or 8% or ATH008 cream placebo
Other Name: ATH008 cream
Placebo Comparator: ATH008 cream placebo
ATH008 cream placebo
Drug: ATH008
The subject will be incorporated in the study and randomised to ATH008 cream 3% or 8% or ATH008 cream placebo
Other Name: ATH008 cream

Detailed Description:

This is a Phase II Placebo Controlled, Multicenter Study that will involve up to 114 patients with Palmar-Plantar Erythrodysesthesia Syndrome (PPES) secondary to capecitabine therapy. Eligible patients will be enrolled into Part I or Part II of the study.

The first part of the study (Part I) is designed

  • to demonstrate the safety of ATH008 cream 1%, 3% and 8% and ATH008 cream placebo,
  • to determine the plasmatic levels of the active ingredient and its metabolite after repeated doses of ATH008 cream 1%, 3% and 8%, and
  • to determine the grade of PPES at Day 1 and Day 21 of ATH008 cream treatment Part I will have four different arms; patients will receive one of the three different doses of drug product (ATH008 cream 1%, ATH008 cream 3% or ATH008 cream 8%) or placebo (ATH008 cream placebo) in repeated doses (twice daily) during a period of 21 days.

Patients will continue to be assessed for safety and pharmacokinetics of active ingredient and its metabolite (Pre-dose, Day 1 and Day 21). Results of Part I will determine the most appropriate and beneficial dose for the second part of the study.

The second part of the study (Part II) is aimed at demonstrating the safety and efficacy of ATH008 cream in reducing the number of patients presenting PPES grade 2/3 secondary to capecitabine therapy following a four times daily application.

Part II will have three different arms; patients will receive ATH008 cream 3%, 8% or placebo in repeated doses (four times per day) since appearance of PPES grade 1 until appearance of grade 2-3 or a maximum of 4 cycles. Patients will continue to be assessed for safety. The clinical signs will be reported by iconographic register of lesions and pain will be evaluated using a pain scale. Patient will fill a questionnaire reporting QoL.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Are under capecitabine monotherapy 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.
  • In Part I, subjects still have to undergo at least 1 planned cycle with capecitabine monotherapy.
  • In Part II, subjects still have to undergo at least 2 planned cycles with capecitabine monotherapy.

Exclusion Criteria:

  • Are younger than 18 years.
  • Use of other chemotherapies for the treatment of cancer except trastuzumab (Herceptin®) or bevacizumab (Avastin®).
  • Diagnosis of PPES grade 1 in any hand or foot according to the NCI CTCAE v4.03 definition for more than 2 cycles previously to inclusion in this clinical study.
  • 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).
  • 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).
  • 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 study treatment.
  • Need to use other emollient creams or other topical treatments in hands and/or feet during the study.
  • Are receiving radiotherapy.
  • Have received topical corticosteroids in hands 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.

The above is not a complete list of eligibility criteria. Please see your study doctor for more information.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01316406

Locations
Belgium
Imelda
Bonheiden, Belgium, 2820
Institute Jules Bordet
Brussels, Belgium, 1000
AZ Maria Middelares
St-Niklaas, Belgium, 9100
Germany
OncoResearch Lerchenfeld UG
Hamburg, Germany
Iniversitätsklinikum Hamburg Eppendorf
Hamburg, Germany
Klinikum Offenbach GmbH
Offenbach, Germany
Prosper Hospital
Recklinghausen, Germany
Italy
IRCCS - Istituto Europeo di Oncologia (IEO) di Milano
Milano, Dr. Franco Nolè, Italy, 20141
A.O. Universitaria Policlinico S.Orsola-Malpighi di Bologna
Bologna, Italy, 40138
Azienda Ospedaliero Universitaria "Maggiore Della Carità" di Novara
Novara, Italy, 28100
Azienda Ospedaliero Universitaria di Sassari
Sassari, Italy, 07100
Spain
Institut Català d'Oncología
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Hospital Puerta de Hierro
Majadahonda, Madrid, Spain, 28222
HGU Alicante
Alicante, Spain, 03010
Hospital del Mar
Barcelona, Spain, 08033
Hospital Vall d'Hebron
Barcelona, Spain, 08035
Complejo Hospitalario Regional Reina Sofia
Córdoba, Spain, 14004
Hospital General de Elche
Elche, Spain, 03203
Hospital Clínic i Provincial
Madrid, Spain, 08036
Hospital Ramón y Cajal
Madrid, Spain, 28049
Hospital Gregorio Marañón
Madrid, Spain, 28007
HGU La Paz
Madrid, Spain, 28046
Hospital de Navarra
Pamplona, Spain, 31008
Hospital de Torrevieja
Torrevieja, Spain, 03186
Institut Valencià d'Oncologia
Valencia, Spain, 46009
Hospital Miguel Servet
Zaragoza, Spain, 50009
Sponsors and Collaborators
Advancell - Advanced In Vitro Cell Technologies, S.A.
CROMSOURCE
Investigators
Principal Investigator: Dr. A. Awada Jules Bordet Institute
  More Information

No publications provided

Responsible Party: Advancell - Advanced In Vitro Cell Technologies, S.A.
ClinicalTrials.gov Identifier: NCT01316406     History of Changes
Other Study ID Numbers: ATH008-CLN02
Study First Received: March 14, 2011
Last Updated: January 29, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Spain: Spanish Agency of Medicines
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Advancell - Advanced In Vitro Cell Technologies, S.A.:
safety
efficacy
treatment
PPES
Palmar-Plantar Erythrodysesthesia Syndrome
Hand-foot syndrome
capecitabine

Additional relevant MeSH terms:
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014