Topical Tretinoin Prophylaxis for Anti-EGFR Induced Skin Toxicity in Metastatic Colorectal Cancer

Inclusion Criteria:

• Participant aged ≥ 18 years

• Histologically confirmed colorectal cancer.

• Radiologically confirmed metastatic disease.

• Eligible for and willing to receive treatment with panitumumab or cetuximab asstandard-of-care.

• ECOG Performance Status ≤ 2.

• Adequate organ function as defined as:

--Hepatic:

• Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)

• AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN ----Participants with livermetastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN.

• Negative pregnancy test for participants who have not undergone surgicalsterilization or shown evidence of post-menopausal status. The followingage-specific requirements apply:

--< 50 years of age:

• Amenorrheic for ≥ 12 months following cessation of exogenous hormonaltreatments; and

• Luteinizing hormone and follicle-stimulating hormone levels in thepost-menopausal range for the institution; or

• Underwent surgical sterilization (bilateral oophorectomy or hysterectomy). --≥ 50 years of age:

• Amenorrheic for 12 months or more following cessation of all exogenous hormonaltreatments; or

• Had radiation-induced menopause with last menses >1 year ago; or

• Had chemotherapy-induced menopause with last menses >1 year ago; or

• Underwent surgical sterilization (bilateral oophorectomy, bilateralsalpingectomy, or hysterectomy).

• Participants of childbearing potential and participants with a sexual partner ofchildbearing potential must agree to use a highly effective method of contraceptionas described in Section 5.4.2.

• Must have recovered from adverse effects of any prior oncologic treatment (e.g.prior surgery, radiotherapy, or other antineoplastic therapy). CTCAE adverse eventsless than or equal to grade 1 are acceptable. CTCAE adverse events grade 2 orgreater may be acceptable as determined by an investigator with appropriatedocumentation.

• Able to provide informed consent and willing to sign an approved consent form thatconforms to federal and institutional guidelines.

Exclusion Criteria:

• Prior treatment with an anti-EGFR agent.

• Pre-existing facial rash with an IGA score of >2 or that per the treatinginvestigator would preclude the ability to assess response to topical tretinoin.

• The diagnosis of another malignancy within ≤ 2 years before study enrollment, exceptfor those considered to be adequately treated with no evidence of disease orsymptoms and/or will not require therapy during the study duration (i.e., basal cellor squamous cell skin cancer, carcinoma in situ of the breast, bladder or of thecervix, or low-grade prostate cancer with Gleason Score ≤ 6).

• Any other condition that would, in the Investigator's judgment, contraindicate theparticipant's participation in the clinical study due to safety concerns orcompliance with clinical study procedures.

• Systemic active infection including tuberculosis (clinical evaluation that includesclinical history, physical examination, radiographic findings, and TB testing inline with local practice), hepatitis B (known positive HBV surface antigen (HBsAg)result), or hepatitis C.

--Note: Participants with a past or resolved HBV infection (defined as the presenceof hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.Participants positive for hepatitis C (HCV) antibody are eligible only if polymerasechain reaction is negative for HCV RNA.

• Medical, psychiatric, cognitive, or other conditions that may compromise theparticipant's ability to understand the participant information, give informedconsent, comply with the study protocol or complete the study.

• Known prior severe hypersensitivity to investigational product or any component inits formulations (CTCAE v5.0 Grade ≥ 3).

• Participants taking prohibited medications as described in Section 6.8.2. A washoutperiod of prohibited medications for a period of at least five half-lives or asclinically indicated should occur before the start of treatment.