Back to resultsSafety and Efficacy Placebo Controlled Study of ATH008 Cream in PPES Patients Secondary to Capecitabine
Primary Purpose
Palmar-Plantar Erythrodysesthesia Syndrome
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ATH008
Sponsored by
About this trial
This is an interventional treatment trial for Palmar-Plantar Erythrodysesthesia Syndrome focused on measuring safety, efficacy, treatment, PPES, Palmar-Plantar Erythrodysesthesia Syndrome, Hand-foot syndrome, capecitabine
Eligibility 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.
Sites / Locations
- Imelda
- Institute Jules Bordet
- AZ Maria Middelares
- Iniversitätsklinikum Hamburg Eppendorf
- OncoResearch Lerchenfeld UG
- Klinikum Offenbach GmbH
- Prosper Hospital
- IRCCS - Istituto Europeo di Oncologia (IEO) di Milano
- A.O. Universitaria Policlinico S.Orsola-Malpighi di Bologna
- Azienda Ospedaliero Universitaria "Maggiore Della Carità" di Novara
- Azienda Ospedaliero Universitaria di Sassari
- Institut Català d'Oncología
- Hospital Puerta de Hierro
- HGU Alicante
- Hospital del Mar
- Hospital Vall d'Hebron
- Complejo Hospitalario Regional Reina Sofia
- Hospital General de Elche
- Hospital Clínic i Provincial
- Hospital Gregorio Marañón
- HGU La Paz
- Hospital Ramón y Cajal
- Hospital de Navarra
- Hospital de Torrevieja
- Institut Valencià d'Oncologia
- Hospital Miguel Servet
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
ATH008 cream 3%
ATH008 cream 8%
ATH008 cream placebo
Arm Description
ATH008 cream 3%
ATH008 cream 8%
ATH008 cream placebo
Outcomes
Primary Outcome Measures
Efficacy of ATH008 cream in reducing the number of subjects presenting PPES grade 2/3 secondary to capecitabine therapy
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
adverse events and serious adverse events (incidence, causality, and severity) related to treatment with ATH008 cream
Plasmatic levels of ATH008 cream when given topically
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
quality of life compared to baseline
Efficacy of ATH008 cream in improving signs and symptoms of PPES
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
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
accumulated capecitabine dose during study treatment (mg / m2) from the starting of ATH008 cream treatment
Full Information
NCT ID
NCT01316406
First Posted
March 14, 2011
Last Updated
January 29, 2014
Sponsor
Advancell - Advanced In Vitro Cell Technologies, S.A.
Collaborators
Cromsource
1. Study Identification
Unique Protocol Identification Number
NCT01316406
Brief Title
Safety and Efficacy Placebo Controlled Study of ATH008 Cream in PPES Patients Secondary to Capecitabine
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.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Advancell - Advanced In Vitro Cell Technologies, S.A.
Collaborators
Cromsource
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Palmar-Plantar Erythrodysesthesia Syndrome
Keywords
safety, efficacy, treatment, PPES, Palmar-Plantar Erythrodysesthesia Syndrome, Hand-foot syndrome, capecitabine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
122 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ATH008 cream 3%
Arm Type
Experimental
Arm Description
ATH008 cream 3%
Arm Title
ATH008 cream 8%
Arm Type
Experimental
Arm Description
ATH008 cream 8%
Arm Title
ATH008 cream placebo
Arm Type
Placebo Comparator
Arm Description
ATH008 cream placebo
Intervention Type
Drug
Intervention Name(s)
ATH008
Other Intervention Name(s)
ATH008 cream
Intervention Description
The subject will be incorporated in the study and randomised to ATH008 cream 3% or 8% or ATH008 cream placebo
Primary Outcome Measure Information:
Title
Efficacy of ATH008 cream in reducing the number of subjects presenting PPES grade 2/3 secondary to capecitabine therapy
Description
percentage of subjects that develop PPES grade 2 or 3 according to the NCI CTCAE v4.03 criteria
Time Frame
minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
Title
Safety of ATH008 cream in patients presenting PPES secondary to capecitabine therapy
Description
adverse events and serious adverse events (incidence, causality, and severity) related to treatment with ATH008 cream
Time Frame
minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
Title
Plasmatic levels of ATH008 cream when given topically
Description
plasmatic levels of the active ingredient and its metabolite when given topically
Time Frame
blood sampling at specific timepoints (Pre-dose, Day 1 and Day 21)
Secondary Outcome Measure Information:
Title
Efficacy of ATH008 cream in improving the quality of life of patients presenting PPES
Description
quality of life compared to baseline
Time Frame
minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
Title
Efficacy of ATH008 cream in improving signs and symptoms of PPES
Description
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
Time Frame
minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
Title
Assessment of patient reported pain
Description
assessment of pain, using a 0-10 score, analysed comparing the values measured during the study treatment period with the baseline pain value
Time Frame
minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
Title
Accumulated dose intensity of capecitabine before and during ATH008 cream treatment
Description
accumulated capecitabine dose during study treatment (mg / m2) from the starting of ATH008 cream treatment
Time Frame
minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. A. Awada
Organizational Affiliation
Jules Bordet Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Imelda
City
Bonheiden
ZIP/Postal Code
2820
Country
Belgium
Facility Name
Institute Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
AZ Maria Middelares
City
St-Niklaas
ZIP/Postal Code
9100
Country
Belgium
Facility Name
Iniversitätsklinikum Hamburg Eppendorf
City
Hamburg
Country
Germany
Facility Name
OncoResearch Lerchenfeld UG
City
Hamburg
Country
Germany
Facility Name
Klinikum Offenbach GmbH
City
Offenbach
Country
Germany
Facility Name
Prosper Hospital
City
Recklinghausen
Country
Germany
Facility Name
IRCCS - Istituto Europeo di Oncologia (IEO) di Milano
City
Milano
State/Province
Dr. Franco Nolè
ZIP/Postal Code
20141
Country
Italy
Facility Name
A.O. Universitaria Policlinico S.Orsola-Malpighi di Bologna
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria "Maggiore Della Carità" di Novara
City
Novara
ZIP/Postal Code
28100
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria di Sassari
City
Sassari
ZIP/Postal Code
07100
Country
Italy
Facility Name
Institut Català d'Oncología
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
HGU Alicante
City
Alicante
ZIP/Postal Code
03010
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08033
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Complejo Hospitalario Regional Reina Sofia
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital General de Elche
City
Elche
ZIP/Postal Code
03203
Country
Spain
Facility Name
Hospital Clínic i Provincial
City
Madrid
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Gregorio Marañón
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
HGU La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
ZIP/Postal Code
28049
Country
Spain
Facility Name
Hospital de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital de Torrevieja
City
Torrevieja
ZIP/Postal Code
03186
Country
Spain
Facility Name
Institut Valencià d'Oncologia
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
Hospital Miguel Servet
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy Placebo Controlled Study of ATH008 Cream in PPES Patients Secondary to Capecitabine
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