Topical Tretinoin for Colon Cancer

(FACE Trial)

Overseen By Susan Sharry

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Disqualifiers: Prior anti-EGFR, Facial rash, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a topical cream called tretinoin can manage acne-like rashes in people with colorectal cancer. These rashes often occur as a side effect of certain cancer treatments. Participants will apply tretinoin to one side of their face and a placebo (a non-active cream) to the other side to determine if tretinoin makes a difference. The trial seeks individuals with colorectal cancer who experience these rashes while undergoing specific cancer treatments like panitumumab or cetuximab. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial requires a washout period (time without taking certain medications) for any prohibited medications, lasting at least five half-lives or as clinically indicated, before starting treatment. The specific medications that are prohibited are not listed in the provided information.

Is there any evidence suggesting that topical tretinoin is likely to be safe for humans?

Research has shown that using topical tretinoin on the skin is generally safe. It has been used for over ten years without causing or increasing cancer risk in people, indicating its likely safety for long-term use. Common side effects are usually mild, including itching, skin pain, and redness. These effects are typical for many skin treatments and are not considered serious. Overall, evidence suggests that tretinoin is generally well-tolerated when applied to the skin. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colon cancer?

Researchers are excited about using topical tretinoin for colon cancer because it represents a novel approach to treatment. Unlike traditional options like chemotherapy or radiation, which target cancer cells systemically or with high-energy particles, tretinoin is a topical retinoid that targets cancer cells through the skin, potentially reducing systemic side effects. This method could offer a less invasive and more targeted treatment option, with the added benefit of being easier on patients. By focusing on a new delivery method and mechanism of action, there’s hope that tretinoin could provide an effective alternative with fewer complications.

What evidence suggests that topical tretinoin might be an effective treatment for acneiform rash in colorectal cancer patients?

Research has shown that all-trans retinoic acid (ATRA), a key component of topical tretinoin, can make colon cancer cells less aggressive. Some studies have also found that tretinoin can enhance the effectiveness of other cancer treatments. Additionally, tretinoin may help prevent or reduce acne-like rashes caused by certain cancer therapies, especially those used in colorectal cancer. This trial will apply tretinoin to one half of the face and a placebo to the other half to evaluate its potential in managing skin-related side effects in cancer patients, potentially improving their overall treatment experience. ^{2 5 6 7 8}

Who Is on the Research Team?

Christopher D. Nevala-Plagemann

Principal Investigator

Huntsman Cancer Institute

Are You a Good Fit for This Trial?

Adults over 18 with metastatic colorectal cancer, who are about to start or are currently receiving panitumumab or cetuximab treatment. They must have good organ function and performance status, not be pregnant, agree to use contraception if applicable, and have recovered from previous cancer treatments.

Inclusion Criteria

My colorectal cancer diagnosis was confirmed through tissue examination.

I am willing to receive treatment with panitumumab or cetuximab.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I am not taking any medications that are not allowed in the study.

I do not have an active infection like TB, hepatitis B, or C.

Known prior severe hypersensitivity to investigational product or any component in its formulations

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topical tretinoin on one side of the face and placebo on the other side to assess the impact on anti-EGFR induced acneiform rash

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Topical Tretinoin

Trial Overview The trial is testing whether topical tretinoin can prevent or reduce skin rash side effects in patients treated with anti-EGFR drugs for colorectal cancer. One side of the face will receive tretinoin while the other side gets a placebo to compare results.

How Is the Trial Designed?

Group I: Tretinoin half of face (right) and Placebo/Moisturizer other half of the face (left) Experimental Treatment 1 Intervention

Randomized, double-blind, split-face. Randomization will determine which side of the face Tretinoin will be applied to (left or right). The other side of the face (left or right) will have placebo applied. All participants will receive both treatment and placebo.

Group II: Tretinoin half of face (left) and Placebo/Moisturizer other half of the face (right) Experimental Treatment 1 Intervention

Randomized, double-blind, split-face. Randomization will determine which side of the face Tretinoin will be applied to (left or right). The other side of the face (left or right) will have placebo applied. All participants will receive both treatment and placebo.

Topical Tretinoin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Tretinoin for:

• Acne
• Psoriasis
• Fine wrinkles
• Mottled hyperpigmentation
• Lentigines

Approved in European Union as Tretinoin for:

• Acne
• Severe psoriasis

Approved in Canada as Tretinoin for:

• Acne
• Psoriasis

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Published Research Related to This Trial

In a multi-institutional study in Japan, tretinoin (ATRA) was highly effective for treating refractory and relapsed acute promyelocytic leukemia, achieving complete remission in 81.5% of previously untreated patients who could not tolerate chemotherapy.

While side effects were common (87.8% of patients experienced issues like skin dryness and headaches), they were generally well tolerated, and serious complications like retinoic acid syndrome were managed effectively, allowing for continued treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Co-operative study of all-trans retinoic acid as a differentiation induction therapy of acute promyelocytic leukemia]. Yamada, O., Hatake, K., Tanimoto, M., et al.[2013]

All-trans-retinoic acid (ATRA) is an effective treatment for acute promyelocytic leukemia, with most side effects being minor except for differentiation syndromes.

The study highlights genital ulcers as an underreported adverse effect of ATRA, emphasizing the need for awareness to prevent serious complications in patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genital ulcers following all-trans-retinoic acid therapy: A case series with review of literature. Saraswat, N., Kumar, S., Prem, R., et al.[2023]

In a study involving 84 patients with facial hyperpigmented lesions, a new nano-atRA gel formulation improved hyperpigmentation in 95.5% of cases after an average treatment duration of 14.3 weeks, with nearly complete elimination in 59.1% of lesions.

The nano-atRA gel caused similar exfoliation and scaling effects as conventional atRA gel but resulted in less erythema, indicating a potentially safer option for patients prone to irritant dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical trial of topical bleaching treatment with nanoscale tretinoin particles and hydroquinone for hyperpigmented skin lesions. Sato, K., Matsumoto, D., Iizuka, F., et al.[2017]

ATRA microspheres (MS) effectively reduced disease symptoms in murine models of inflammatory bowel disease (IBD), suggesting a promising treatment option with fewer systemic side effects compared to traditional oral ATRA.

The ATRA MS formulation demonstrated superior efficacy and better pharmacokinetics than soluble ATRA, indicating that targeted delivery to the gut may enhance therapeutic outcomes for IBD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Delivery of Encapsulated All-Trans Retinoic Acid Ameliorates Disease in Rodent Models of Colitis. Nicoletti, F., Hammer, L., Furtado, S., et al.[2022]

The study demonstrated that incorporating all-trans-retinoic acid (ATRA) into 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) significantly enhances its aqueous solubility and photostability, which are crucial for developing effective formulations.

These findings suggest that a parenteral or aqueous oral formulation of ATRA could be feasible, but further evaluation of its biopharmaceutical properties is needed before clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2-hydroxypropyl-beta-cyclodextrin increases aqueous solubility and photostability of all-trans-retinoic acid. Lin, HS., Chean, CS., Ng, YY., et al.[2019]

Topical all-trans retinoic acid (tretinoin) 0.1% showed improvement in symptoms and signs for all eight patients with various ocular surface disorders, including those following Stevens-Johnson syndrome and chronic kerato conjunctivitis.

While the treatment was effective, some patients experienced local irritation, and challenges with formulation and stability need to be addressed before broader use of topical retinoids can be implemented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical retinoic acid therapy for disorders of the outer eye. Wright, P.[2013]

In a study involving 28 female nude mice, dietary vitamin A supplementation significantly reduced the number of liver metastases from ATRA-resistant colon cancer cells to 17% of the control group, suggesting its potential as a therapeutic strategy.

The vitamin A supplementation did not cause any adverse effects, such as weight loss or toxicity, indicating it is a safe option for potentially reducing cancer metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic vitamin A preloading reduces colorectal cancer metastatic multiplicity in a mouse xenograft model. Park, EY., Pinali, D., Lindley, K., et al.[2021]

All three tested retinoids (ATRA, 9-cis, and 13-cis retinoic acid) effectively reduced the expression of matrilysin, an enzyme linked to the invasion of colon cancer cells, in both laboratory and mouse models.

The retinoids suppressed the invasiveness of colon cancer cell lines and reduced tumor invasion in mice without affecting overall tumor growth, suggesting their potential as therapeutic agents in managing colorectal carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinoic acids reduce matrilysin (matrix metalloproteinase 7) and inhibit tumor cell invasion in human colon cancer. Adachi, Y., Itoh, F., Yamamoto, H., et al.[2018]

The review of nine retinoids for cancer prevention found that all-trans-retinoic acid, 13-cis-retinoic acid, and N-ethylretinamide are not suitable for human use due to toxicity, potential to enhance cancer, or ineffectiveness.

Conversely, 9-cis-retinoic acid, etretinate, and acitretin show some potential for cancer prevention, but further research is needed, while all-trans N-(4-hydroxyphenyl)retinamide appears particularly promising.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An International Evaluation of the Cancer-Preventive Potential of Nine Retinoids. Miller, AB., Nettesheim, P., Stewart, BW.[2019]

All-trans retinoic acid (ATRA) significantly inhibits the growth of HT29 colon carcinoma cells in a way that does not induce differentiation, suggesting a unique mechanism of action against cancer cell proliferation.

The growth-inhibiting effects of ATRA are primarily mediated through the retinoic acid receptor alpha (RARalpha), as shown by the ability of a selective RARalpha agonist to replicate ATRA's effects and the complete blockage of these effects by a RARalpha antagonist.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinoic acid receptor alpha mediates growth inhibition by retinoids in human colon carcinoma HT29 cells. Nicke, B., Kaiser, A., Wiedenmann, B., et al.[2013]

All-trans-retinoic acid (ATRA) is an effective treatment for acute promyelocytic leukemia, but it can cause side effects such as retinoic acid syndrome and Sweet's syndrome.

This report highlights a rare case of hypercalcemia in a patient treated with ATRA, potentially linked to the interaction with voriconazole, which inhibits cytochrome P450 function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypercalcemia due to all trans retinoic acid in the treatment of acute promyelocytic leukemia potentiated by voriconazole. Bennett, MT., Sirrs, S., Yeung, JK., et al.[2019]

Topical tretinoin, a form of vitamin A, has demonstrated antitumor effects in various studies, effectively removing premalignant actinic keratoses and showing potential in treating skin lesions when combined with 5-fluorouracil.

Importantly, after over a decade of use, tretinoin has not been found to cause or promote cancer in humans, indicating its safety in long-term topical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

All-trans-retinoic acid and cutaneous cancers. Epstein, JH.[2019]

Citations

1. withpower.com withpower.com/trial/phase-2-rectal-neoplasms-6-2024-91d03

Topical Tretinoin for Colon Cancer (FACE Trial) Research shows that all-trans retinoic acid (ATRA), a component of Topical Tretinoin, can reduce the invasiveness of colon cancer cells and decrease the number ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10865642/

Tretinoin improves the anti-cancer response to ... As we observed that the addition of tretinoin significantly increased CY efficacy in AB1HA mesothelioma, we tested whether this treatment worked ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7465813/

Current Trends in ATRA Delivery for Cancer Therapy - PMC This up-to-date review deals with recent studies on different ATRA-loaded Drug Delivery Systems (DDSs) development and application on several tumor models.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-03602

Topical Tretinoin for the Prevention of Anti-EGFR Induced ... Topical tretinoin may prevent or reduce the development of an acneiform rash among patients receiving anti-EGFR treatment for metastatic colorectal cancer.

5. nature.com nature.com/articles/s41467-020-18042-2

Advances and challenges in retinoid delivery systems ... In the last application, the remission rate (67% clinical remission) was lower than that obtained using a combinatorial therapy (77% clinical ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06358677

Topical Tretinoin Prophylaxis for Anti-EGFR Induced Skin ... The goal of this clinical trial is to learn if using topical tretinoin will help patients with colorectal cancer who are experiencing an acneiform rash as a ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK557478/

Tretinoin - StatPearls - NCBI Bookshelf - NIH According to the FDA drug labeled guidelines, the most common adverse effects in topically administered tretinoin are the following: pruritus, skin pain, skin/ ...

8. trialx.com trialx.com/clinical-trials/listings/319405/topical-tretinoin-prophylaxis-for-anti-egfr-induced-skin-toxicity-in-metastatic-colorectal-cancer/

Topical Tretinoin Prophylaxis for Anti-EGFR Induced Skin ... The goal of this clinical trial is to learn if using topical tretinoin will help patients with colorectal cancer who are experiencing an acneiform rash as a ...