NCT03167268: PaSTo

Panitumumab Skin Toxicity Prevention Trial

Status unknown Phase 2 Last updated 9 September 2021

What this trial tests

Phase 2 trial testing Lycopene in Colorectal Cancer Metastatic in 28 participants. Status unknown.

Timeline

3 August 2016

Primary endpoint
13 January 2020

30 November 2021

Quick facts

Lead sponsor	Ospedale San Carlo Borromeo
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	supportive care
Enrollment	28
Start date	3 August 2016
Primary completion	13 January 2020
Estimated completion	30 November 2021
Sites	1 location across Italy

Drugs / interventions tested

• Lycopene (LYCOPENE) — full drug profile →
• Placebo

Conditions studied

• Colorectal Cancer Metastatic — all drugs for Colorectal Cancer Metastatic →
• Skin Toxicity — all drugs for Skin Toxicity →

Sponsor

Ospedale San Carlo Borromeo

Who can join

18 and older, any sex, with Colorectal Cancer Metastatic or Skin Toxicity. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Phytochemicals in Cancer Treatment: From Preclinical Studies to Clinical Practice.
   Choudhari AS, Mandave PC, Deshpande M, Ranjekar P, et al · · 2019 · cited 560× · PMID 32116665 · DOI 10.3389/fphar.2019.01614
2. Targeting GSK3 and Associated Signaling Pathways Involved in Cancer.
   Duda P, Akula SM, Abrams SL, Steelman LS, et al · · 2020 · cited 190× · PMID 32365809 · DOI 10.3390/cells9051110
3. Traditional Chinese Medicine and Colorectal Cancer: Implications for Drug Discovery.
   Sun Q, He M, Zhang M, Zeng S, et al · · 2021 · cited 40× · PMID 34276374 · DOI 10.3389/fphar.2021.685002
4. Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation.
   Tufail M, Jiang CH, Li N. · · 2025 · cited 36× · PMID 40170063 · DOI 10.1186/s12943-025-02306-w
5. The Anticancer Potential of Plant-Derived Nutraceuticals via the Modulation of Gene Expression.
   Vrânceanu M, Galimberti D, Banc R, Dragoş O, et al · · 2022 · cited 28× · PMID 36235389 · DOI 10.3390/plants11192524
6. Reactive oxygen species mediated apoptotic death of colon cancer cells: therapeutic potential of plant derived alkaloids.
   Nelson VK, Nuli MV, Mastanaiah J, Saleem T S M, et al · · 2023 · cited 22× · PMID 37560308 · DOI 10.3389/fendo.2023.1201198
7. Phytocompounds targeting epigenetic modulations: an assessment in cancer.
   Khan A, Khan A, Khan MA, Malik Z, et al · · 2023 · cited 20× · PMID 38596245 · DOI 10.3389/fphar.2023.1273993
8. Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals.
   Son SW, Lee HY, Moeng S, Kuh HJ, et al · · 2020 · cited 15× · PMID 33066509 · DOI 10.3390/molecules25204701