Palmar-Plantar Erythrodysesthesia SyndromePhase 2NCT01316406
Safety and Efficacy Placebo Controlled Study of ATH008 Cream in PPES Patients Secondary to Capecitabine
A Phase 2 study testing ATH008 in people with Palmar-Plantar Erythrodysesthesia Syndrome, run by Advancell - Advanced In Vitro Cell Technologies, S.A. at 26 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Palmar-Plantar Erythrodysesthesia Syndrome
- What is being tested?
- ATH008
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 26 sitesin 4 countries
- Study dates
- Feb 2011to Aug 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
26 sites in 4 countries.
26 sites in 4 countries
Spain15 sites
HGU Alicante
Alicante, 03010
Hospital del Mar
Barcelona, 08033
Hospital Vall d'Hebron
Barcelona, 08035
Complejo Hospitalario Regional Reina Sofia
Córdoba, 14004
Hospital General de Elche
Elche, 03203
Institut Català d'Oncología
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital Clínic i Provincial
Madrid, 08036
Hospital Gregorio Marañón
Madrid, 28007
HGU La Paz
Madrid, 28046
Hospital Ramón y Cajal
Madrid, 28049
Hospital Puerta de Hierro
Majadahonda, Madrid, 28222
Hospital de Navarra
Pamplona, 31008
Hospital de Torrevieja
Torrevieja, 03186
Institut Valencià d'Oncologia
Valencia, 46009
Hospital Miguel Servet
Zaragoza, 50009
Germany4 sites
Iniversitätsklinikum Hamburg Eppendorf
Hamburg
OncoResearch Lerchenfeld UG
Hamburg
Klinikum Offenbach GmbH
Offenbach
Prosper Hospital
Recklinghausen
Italy4 sites
A.O. Universitaria Policlinico S.Orsola-Malpighi di Bologna
Bologna, 40138
IRCCS - Istituto Europeo di Oncologia (IEO) di Milano
Milan, Dr. Franco Nolè, 20141
Azienda Ospedaliero Universitaria "Maggiore Della Carità" di Novara
Novara, 28100
Azienda Ospedaliero Universitaria di Sassari
Sassari, 07100
Belgium3 sites
Imelda
Bonheiden, 2820
Institute Jules Bordet
Brussels, 1000
AZ Maria Middelares
St-Niklaas, 9100
About this study
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.
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.
Read the 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.
- Being tested
- ATH008
- Keywords
- safety, efficacy, treatment, PPES, Palmar-Plantar Erythrodysesthesia Syndrome, Hand-foot syndrome, capecitabine
- Medical subject headings
- Hand-Foot Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATH008Drug
Also called ATH008 cream
The subject will be incorporated in the study and randomised to ATH008 cream 3% or 8% or ATH008 cream placebo
| Study group | Role | What they receive |
|---|---|---|
| ATH008 cream 3% | Experimental | ATH008 cream 3% Receives: Drug: ATH008 |
| ATH008 cream 8% | Experimental | ATH008 cream 8% Receives: Drug: ATH008 |
| ATH008 cream placebo | Placebo comparator | ATH008 cream placebo Receives: Drug: ATH008 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
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
Measured: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
Plasmatic levels of ATH008 cream when given topically
plasmatic levels of the active ingredient and its metabolite when given topically
Measured: blood sampling at specific timepoints (Pre-dose, Day 1 and Day 21)
Secondary outcomes (4)
Efficacy of ATH008 cream in improving the quality of life of patients presenting PPES
quality of life compared to baseline
Measured: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
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
Measured: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
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
Measured: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
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
Measured: minimum every 21 days, maximum of 4 capecitabine cycles, followed by a safety observation period of 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2011 (estimated)
- Study startFeb 2011
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Palmar-Plantar Erythrodysesthesia SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advancell - Advanced In Vitro Cell Technologies, S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cromsource
- Responsible party
- Sponsor
- Investigators
- Dr. A. Awada, Principal investigator, Jules Bordet Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01316406
- Sponsor's protocol ID
- ATH008-CLN02
- Status last verified
- Jan 2014
- First submitted
- 14 Mar 2011
- Last updated
- 30 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01316406
- Acronym / sponsor ID
- ATH008-CLN02
- Keywords
- safety, efficacy, treatment, PPES, Palmar-Plantar Erythrodysesthesia Syndrome, Hand-foot syndrome, capecitabine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Advancell - Advanced In Vitro Cell Technologies, S.A.Industry (pharma, biotech, devices)
- Collaborators
- Cromsource
- Study start
- Feb 2011
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 16 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ATH008 cream 3% | Experimental | Drug: ATH008ATH008 cream 3% |
| ATH008 cream 8% | Experimental | Drug: ATH008ATH008 cream 8% |
| ATH008 cream placebo | Placebo comparator | Drug: ATH008ATH008 cream placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (12 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ATH008Also: ATH008 creamThe subject will be incorporated in the study and randomised to ATH008 cream 3% or 8% or ATH008 cream placebo | Drug | ATH008 cream 3%, ATH008 cream 8%, ATH008 cream placebo |
Primary outcome
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
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
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)
plasmatic levels of the active ingredient and its metabolite when given topically
4 secondary outcomes
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. A. Awada principal investigator
Jules Bordet Institute
26 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ATH008 in people with Palmar-Plantar Erythrodysesthesia Syndrome, run by Advancell - Advanced In Vitro Cell Technologies, S.A. at 26 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Spain, Germany, Italy, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2014.