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Panitumumab Skin Toxicity Prevention Trial (PaSTo)

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ClinicalTrials.gov Identifier: NCT03167268
Recruitment Status : Recruiting
First Posted : May 25, 2017
Last Update Posted : May 25, 2017
Sponsor:
Information provided by (Responsible Party):
DR. MAURO MORONI, Ospedale San Carlo Borromeo

Brief Summary:

Background and rationale: EGFR represents the main and more studied signal activation pathway in the development of colorectal carcinoma. KRAS, NRAS, BRAF and PI3KA mutations and ERBB2 and MET amplification are responsible for most of the cases of primary resistance to anti-EGFR antibody treatments. Despite the identification of these resistance mechanisms, a primary resistance to the therapy was detected in a certain percentage of cases, in which tumour bio-molecular characteristics would suggest a possible response to anti-EGFR antibody treatment. In these cases, pathway activation mechanisms should exist, which act in an alternative, complementary or parallel way than the EGFR one, allowing tumour progression despite of EGFR pharmacological deactivation. Skin toxicity is a characteristic of drugs having EGFR as a target and it shows itself mainly as a sterile acneiform folliculitis together with neutrophils perifollicular infiltrates but also as skin xerosis and paronychia starting from the earliest cycles of treatment. This skin toxicity seems to be closely related to EGFR activation of pro-inflammatory cytokines able to activate specific inflammatory activators, which induce neutrophils granulocytes chemotaxis. Lycopene is a compound belonging to carotenoid group, largely contained in tomatoes and their derivatives, which has an extreme antioxidant activity. In Dermatology, prolonged use of β-carotenoids in general and of lycopene in particular in the diet showed to be effective in skin protection from ageing, sunlight and radiotherapy damages because these compounds may accumulate in skin and thus contribute to reduce free radicals and inflammation effects. Moreover, lycopene ability to induce apoptosis and to inhibit cell cycle progression in some types of tumour cells, both in vitro and in vivo, has already been described. Lycopene seems to be able to suppress significantly PCNA (Proliferating cell nuclear antigen, cofactor of DNA polymerase-β) and β-catenin nuclear expression in neoplastic cells, essential substrate of WNT/β-catenin pathway, which is itself closely connected to activating pathways often involved in carcinogenesis of some kinds of tumours, in particular of colorectal carcinoma, like Akt/GSK3β/β-catenin and Hippo pathways. For its proved skin anti-inflammatory activity as powerful free radicals scavenger, lycopene, which accumulates itself specifically in skin, could be effective in reducing anti-EGFR drugs toxicity. Contemporary use of lycopene could have a positive effect on anti-EGFR drugs treatment effectiveness in patients with metastatic colorectal carcinoma due to its ability to interfere with pathways involved in neoplastic cells proliferation.

Estimated population:100 patients (50 for each of the two groups of treatment)

Study Framework: In this study, patients suffering from metastatic colorectal cancer and submitted to therapy with panitumumab would be enrolled. According to indications, panitumumab would be used:

in first line combined with Folfox or Folfiri;

in second line combined with Folfiri or treatments containing Irinotecan

in monotherapy in any therapeutic line in patients resistant to Fluoropyrimidines, Oxaliplatin and Irinotecan or intolerant to these drugs.

Standard schedules of these treatments would be used.

This is a phase-II, randomized, double-blind study between experimental prophylactic treatment with Lycopene vs placebo:

  • Treatment A - lycopene tablets 20 mg
  • Treatment B - placebo tablets

Patients should take orally Lycopene/placebo after dinner (to promote its absorption), starting the day before the beginning of treatment with panitumumab for the entire duration of the therapy, until progression of the disease or definitive drug suspension for toxicity.

Objectives of the study

Primary objective: to assess the effectiveness of lycopene versus placebo in reducing skin toxicity induced by panitumumab in patients treated for metastatic colorectal carcinoma.

Secondary objective: to assess lycopene pharmacokinetics

Exploratory objectives: to assess lycopene effectiveness versus placebo in increasing panitumumab effectiveness in terms of Disease Control (DC), Objective Response (OR) and Stabilisation of the Disease (SD). To assess lycopene effectiveness versus placebo in increasing panitumumab effectiveness in terms of Progression Free Survival (PFS).

As far as randomization is concerned, the two groups will be balanced according to sex, therapeutic line and institution in which patients will be treated.


Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastatic Skin Toxicity Drug: Lycopene Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind study
Primary Purpose: Supportive Care
Official Title: Double-blind, Phase II Study to Assess the Effectiveness of Lycopene vs Placebo to Reduce Skin Toxicity in Patients With Colorectal Carcinoma Treated With Panitumumab
Actual Study Start Date : August 3, 2016
Estimated Primary Completion Date : May 31, 2019
Estimated Study Completion Date : November 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Lycopene 20mg cpr/die
Lycopene is a compound belonging to carotenoid group, largely contained in tomatoes and their derivatives, which has an extreme antioxidant activity. In Dermatology, prolonged use of β-carotenoids in general and of lycopene in particular in the diet showed to be effective in skin protection from ageing, sunlight and radiotherapy damages because these compounds may accumulate in skin and thus contribute to reduce free radicals and inflammation effects.
Drug: Lycopene
Placebo Comparator: Placebo
Containing same excipients than the experimental "Lycopene 20 mg" but not active principle (Lycopene)
Other: Placebo



Primary Outcome Measures :
  1. Skin toxicity reduction [ Time Frame: Skin toxicity will be verified every two weeks assessed up to 12 weeks, from date of randomization until the date of first documented progression ]

    Reduction of grade 2/4 skin toxicity of 30% in the experimental group.

    Toxicity will be evaluated as:

    1. worst toxicity for each patient during the treatment;
    2. grade 3 or grade 4 toxicity duration related to the treatment duration for each patient in the two arms;
    3. number and duration of tetracyclines and antibiotic treatment related to the treatment duration for each patient in the two arms;
    4. toxicity in difference time points (G15, G29, .....) for each clinical skin features (rash papular, pustular - xerosis skin - paronychia) in the two arms



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Standard schedules of these treatments would be used.

Inclusion and exclusion criteria would be the following:

Inclusion criteria:

  1. Age ≥ 18 years;
  2. Patients suffering from colorectal adenocarcinoma at stage-IV, for which a treatment with panitumumab is required;
  3. No previous treatment with anti-EGFR drugs;
  4. Presence of at least one neoplastic lesion one-dimensionally measurable;
  5. No systemic anti-neoplastic therapy, nor experimental therapy or radiotherapy during the three weeks before randomization;
  6. Proper contraceptive treatment by patient and his/her partner;
  7. Written informed consent for participating to the study;
  8. Performance Status (under ECOG scale) 0, 1. 2.

Exclusion criteria

  1. PS > 2
  2. Poor patient compliance;
  3. Dermatological ongoing pathologies which contraindicate the treatment or made skin toxicity assessment difficult;
  4. Presence of clinical conditions which could alter lycopene absorption (altered intestinal transit, malabsorption);
  5. Pregnancy;
  6. Absence of measurable lesions;
  7. Previous treatment with anti-EGFR drugs;
  8. Intolerance/allergy to tomato or milk.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03167268


Contacts
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Contact: Mauro moroni, MD +390240222119 ext 2668 mauro.moroni@asst-santipaolocarlo.it

Locations
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Italy
Marco Pirovano Recruiting
Milano, Italy, 20153
Contact: Marco Pirovano, MD    +390240222108    marco.pirovano@asst-santipaolocarlo.it   
Sponsors and Collaborators
Ospedale San Carlo Borromeo

Publications of Results:

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Responsible Party: DR. MAURO MORONI, Director of Oncology Unit, Ospedale San Carlo Borromeo
ClinicalTrials.gov Identifier: NCT03167268     History of Changes
Other Study ID Numbers: PaSTo
First Posted: May 25, 2017    Key Record Dates
Last Update Posted: May 25, 2017
Last Verified: May 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by DR. MAURO MORONI, Ospedale San Carlo Borromeo:
Lycopene
Anti EGFR therapy

Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Panitumumab
Lycopene
Antineoplastic Agents, Immunological
Antineoplastic Agents
Anti-Inflammatory Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Radiation-Protective Agents
Anticarcinogenic Agents