Topical Tretinoin for Colon Cancer
(FACE Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Utah
Disqualifiers: Prior anti-EGFR, Facial rash, Others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?
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 side effect of their treatment. Researchers will compare the use of tretinoin on one side of the face to the use of a placebo on the other side of the face to see if there is an impact.
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.
What evidence supports the effectiveness of the drug Topical Tretinoin for colon cancer?
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 of liver metastases in animal models. Additionally, ATRA has been found to inhibit the growth of colon cancer cells by targeting specific receptors involved in cancer cell growth.12345
Is topical tretinoin generally safe for humans?
Topical tretinoin (all-trans-retinoic acid) has been used in various treatments and is generally well-tolerated, but it can cause skin irritation and dryness. In some cases, it has been associated with more serious side effects like hypercalcemia (high calcium levels in the blood) and genital ulcers, especially when used in combination with other medications.46789
How is the drug Topical Tretinoin unique for treating colon cancer?
Topical Tretinoin is unique for colon cancer treatment because it is applied directly to the skin, unlike most cancer treatments that are taken orally or intravenously. This method may help reduce systemic side effects, which are common with oral formulations of tretinoin used for other conditions.14101112
Eligibility Criteria
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 am 18 years old or older.
See 7 more
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
See 5 more
Trial Timeline
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
Treatment Details
Interventions
- Topical Tretinoin (Retinoid)
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Tretinoin half of face (right) and Placebo/Moisturizer other half of the face (left)Experimental Treatment1 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 Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Huntsman Cancer Institute at University of UtahSalt Lake City, UT
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Who Is Running the Clinical Trial?
University of UtahLead Sponsor
References
Hepatic vitamin A preloading reduces colorectal cancer metastatic multiplicity in a mouse xenograft model. [2021]Previous research in our laboratory showed that retinol inhibited all-trans retinoic acid (ATRA)-resistant human colon cancer cell invasion via a retinoic acid receptor-independent mechanism in vitro. The objective of the current study was to determine if dietary vitamin A supplementation inhibited metastasis of ATRA-resistant colon cancer cells in a nude mouse xenograft model. Female nude mice (BALB/cAnNCr-nu/nu, n = 14 per group) consumed a control diet (2,400 IU retinyl palmitate/kg diet) or a vitamin A supplemented diet (200,000 IU retinyl palmitate/kg diet) for 1 mo prior to tumor cell injection to preload the liver with vitamin A. HCT-116, ATRA-resistant, human colon cancer cells were intrasplenically injected. Mice continued to consume their respective diets for 5 wk following surgery. Consumption of supplemental vitamin A decreased hepatic metastatic multiplicity to 17% of control. Hepatic and splenic retinol and retinyl ester concentrations were significantly higher in the mice supplemented with vitamin A when compared to mice consuming the control diet. Supplemental vitamin A did not decrease body weight, feed intake, or cause toxicity. Thus, supplemental dietary vitamin A may decrease the overall number of hepatic metastasis resulting from colon cancer.
Retinoic acids reduce matrilysin (matrix metalloproteinase 7) and inhibit tumor cell invasion in human colon cancer. [2018]All-trans retinoic acid (ATRA), 9-cis retinoic acid and 13-cis retinoic acid are naturally occurring retinoids used in the prevention and therapy of various preneoplastic and neoplastic diseases. It was previously reported that matrilysin, one of the matrix metalloproteinases (MMP-7), plays a critical role in the invasion and metastasis of gastrointestinal cancers. Moreover, it has been shown that ATRA downregulates matrilysin expression and prevents in vitro invasion by colon cancer cells. In this study, three retinoids were used, both in Matrigel invasion assays and in subcutaneous xenografts in mice, to evaluate the effects of retinoids on invasion by colon cancer cell lines (CHC-Y1, DLD-1, HT-29, BM314, CaR-1 and WiDr). All three retinoic acids tested reduced matrilysin expression and suppressed the invasiveness of colon cancer cell lines in vitro. Retinoic acids also reduced tumor invasion in mice without influencing tumor growth. Matrilysin expression in these tumors was clearly reduced. These data support the use of retinoic acids as useful reagents to manage patients with colorectal carcinoma.
All-trans-retinoic acid and cutaneous cancers. [2019]All-trans-retinoic acid (tretinoin) is a biologically active metabolite of vitamin A. Topical tretinoin has been shown to have antineoplastic activity in a variety of experimentally induced and naturally occurring tumors. In some animal studies it has inhibited the development of ultraviolet-induced carcinomas. However, in other studies it accelerated such ultraviolet tumorigenesis. Other work has shown that the drug can eradicate chemically induced papillomas and carcinomas. These various effects may stem from tretinoin's influences on deoxyribonucleic acid synthesis, polyamine enzyme systems, sister-chromatid exchanges, oncogene expression, or lysosome lability. In clinical trials, tretinoin removed premalignant actinic keratoses from the face. Combined with 5-fluorouracil, it is also quite effective in the treatment of such lesions on the forearms and hands, areas where neither agent alone has much effect. It should be emphasized that tretinoin has not been shown to be carcinogenic in either animals or humans. After more than a decade of topical use of tretinoin on human skin, there is no evidence that the drug either initiates or promotes carcinogenesis in humans.
An International Evaluation of the Cancer-Preventive Potential of Nine Retinoids. [2019]The International Agency for Research on Cancer (IARC) convened a working Group of experts in March 1999 to evaluate the cancer preventive potential of nine retinoids and to compile the fourth volume of the IARC Handbooks of Cancer Prevention. The handbook provides a comprehensive review of the relevant information in the published scientific literature through March 1999 on the potential role of all-trans-retinoic acid, 13-cis-retinoic acid, 9-cis-retinoic acid, all-trans N-(4-hydroxyphenyl)retinamide, etretinate, acitretin, N-ethylretinamide, targretin and LGD 1550 in cancer prevention. Of these, the data suggest that all-trans-retinoic acid, 13-cis-retinoic acid and N-ethylretinamide are not suitable for chemoprevention of cancer in humans either because they are too toxic, may enhance cancer occurrence or are ineffective. In contrast, 9-cis-retinoic acid, etretinate and acitretin show some promise, but more data are required, while all- trans N-(4-hydroxyphenyl)retinamide is quite promising. Targretin and LGD 1550 are of interest, based on theoretical grounds, but there are no significant human and little experimental data as yet.
Retinoic acid receptor alpha mediates growth inhibition by retinoids in human colon carcinoma HT29 cells. [2013]Although retinoids have been suggested to inhibit chemically induced colon carcinogenesis, the molecular mechanisms underlying retinoid-mediated growth regulation in colon carcinoma cells are unknown. Therefore, we investigated the biological effects of retinoids on growth in HT29 colon carcinoma cells. All-trans retinoic acid (ATRA) treatment of HT29 cells resulted in a profound inhibition of anchorage-independent growth without biochemical or morphological evidence for induction of differentiation. Treatment with the selective RARalpha agonist Ro 40-6055 completely mimicked the effects of ATRA on growth and transactivation of a betaRAREx2-luciferase reporter construct, while RARbeta- and gamma-specific analogues were ineffective. Furthermore, ATRA-regulated growth and transactivation could be completely blocked by a RARalpha-selective receptor antagonist. Thus, ATRA potently inhibits anchorage-independent growth in HT29 cells and this effect is mainly if not exclusively mediated by the retinoic acid receptor alpha.
Hypercalcemia due to all trans retinoic acid in the treatment of acute promyelocytic leukemia potentiated by voriconazole. [2019]All-trans-retinoic acid (ATRA) is a new and effective treatment of acute promyelocytic leukemia. It has many side-effects, including the retinoic acid syndrome and Sweet's syndrome. There have been only nine cases of hypercalcemia associated with ATRA described in the literature. We discuss a case of hypercalcemia, which we believe was due to inhibition of cytochrome P450 function by voriconizole when used concomitantly with ATRA.
Genital ulcers following all-trans-retinoic acid therapy: A case series with review of literature. [2023]All-trans-retinoic acid (ATRA) has transformed the treatment of acute promyelocytic leukemia. Most of the adverse effects associated with this drug are minor barring differentiation syndromes. Genital ulcers feature among the underreported adverse effects of ATRA which needs to be kept in mind to avoid life-threatening complications. We describe two cases who developed genital ulcers while treated with ATRA.
[Co-operative study of all-trans retinoic acid as a differentiation induction therapy of acute promyelocytic leukemia]. [2013]Efficacy and safety of tretinoin (all-trans retinoic acid, ATRA, Ro01-5488) for refractory and relapsed acute promyelocytic leukemia were studied by multi-institutional study in Japan. 22 out of 27 (81.5%) patients with previously untreated who were intolerable to chemotherapy, relapsed and refractory were achieved CR. And 4 out of 11 (36.4%) in relapsed patients who received ATRA remission induction therapy previously responded. Side effects, such as dryness of the lip and skin, headache, increase of triglyceride, beta-lipoprotein and lactate dehydrogenase, were observed in 36 of 41 eligible patients (87.8%) but these were well tolerated. In addition to these, hyperleukocytosis in 4 cases and retinoic acid syndrome in 3 cases were observed. However, all patients were prescribed tretinoin again by adequate management.
A clinical trial of topical bleaching treatment with nanoscale tretinoin particles and hydroquinone for hyperpigmented skin lesions. [2017]Although combined use of tretinoin (all-trans-retinoic acid; atRA) and hydroquinone improves various hyperpigmented lesions, the pharmacologic instability of atRA and atRA-induced irritant dermatitis are difficult unsolved problems.
Oral Delivery of Encapsulated All-Trans Retinoic Acid Ameliorates Disease in Rodent Models of Colitis. [2022]All-trans retinoic acid (ATRA) is a biologically active isomer of retinoic acid (RA). Topical ATRA (retin-a, retin-a micro, atralin, renova, and avita) is the active pharmaceutical ingredient for FDA-approved treatments for acne and skin wrinkles. Oral formulations (Vesanoid) treat acute promyelocytic leukemia, but oral dosing can induce severe side effects. Despite benefits in various rodent models of inflammatory bowel disease (IBD), toxicity and controversial clinical observations have diminished enthusiasm for ATRA IBD clinical trials. To circumvent these issues and to use ATRA's key role in maintaining gut tolerance, we developed a poly(lactic-co-glycolic acid) (PLGA) microsphere (MS) encapsulated ATRA formulation aimed at directing ATRA delivery to immune structures of the gut, limiting systemic exposure. Initially, ATRA MS was developed as a component of a combinatorial product (TreXTAM) that also contained encapsulated transforming growth factor (TGF)-β and ATRA in a 1:2 w/w ratio. Although the combination was optimal, benefit was also observed when ATRA MS was given alone in the CD4+ CD25-T-cell adoptive transfer (ACT) colitis model.
2-hydroxypropyl-beta-cyclodextrin increases aqueous solubility and photostability of all-trans-retinoic acid. [2019]All-trans-retinoic acid (ATRA, vitamin A acid or tretinoin) is effective in the treatment of acute promyelocytic leukaemia (APL). Unfortunately, the oral absorption of ATRA is highly variable. Its poor aqueous solubility also makes it difficult to be formulated into parenteral formulation. To date, there is no parenteral formulation of ATRA available commercially.
Topical retinoic acid therapy for disorders of the outer eye. [2013]Topical all trans retinoic acid (tretinoin) 0.1 per cent has been used to treat eight patients with squamous metaplasia and keratinisation of the conjunctiva. In four patients the changes followed Stevens-Johnson syndrome, one patient had chronic atopic kerato conjunctivitis, one had persistent epithelial erosions following sarcoid related kerato conjunctivitis sicca complicated by preservative induced epithelial toxicity, one had a recurrent Bowen like epithelial dysplasia and one had an unclassifiable primary ocular surface disorder. Improvement in symptoms and signs were noted in all patients but local irritation developed in some and the optimum dosage remains to be determined. Problems of formulation and stability of the preparation need to be solved before topical retinoid therapy can be more widely used.