A Trial of All-trans Retinoic Acid (ATRA) in Advanced Adenoid Cystic Carcinoma

Inclusion Criteria: * Participants must have histologically confirmed adenoid cystic carcinoma with evidence of recurrent, metastatic or advanced, unresectable disease that is not amenable to curative surgery with or without radiotherapy. * Participants must have at least one RECIST v1.1 measurable non-CNS based lesion, as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) equal to or greater than 1 cm with CT scans or MR imaging. * Participants must be willing to undergo fresh tissue core needle biopsy prior to study registration and repeat tumor biopsy while on study for correlatives. Willingness to provide blood samples for research throughout the study is also required. * Prior systemic therapy: At least 2 weeks must have elapsed since the end of prior chemotherapy, biological agents (4 weeks for anti-cancer monoclonal antibody containing regimens) or any investigational drug product, with adequate recovery of treatment-related toxicity to NCI CTCAE Version 5.0 grade ≤ 1 (or tolerable grade 2) or back to baseline (except for alopecia or neuropathy). Any number of prior therapies for recurrent/metastatic ACC are permitted. * Be ≥ 18 years of age on day of signing informed consent. * Have a performance status of 0 or 1 on the ECOG Performance Scale (see Appendix A). * Participants must have documentation of a new or progressive lesion on a radiologic imaging study performed within 12 months prior to study registration (progression of disease over any interval is allowed) and/or new or worsening disease-related symptoms within 12 months prior to study registration. This assessment is performed by the treating investigator. Evidence of progression by RECIST v1.1 criteria is not required. * Participants must have normal organ and marrow function as defined below (within 14 days prior to study registration): * leukocytes ≥ 3,000/mcL * absolute neutrophil count ≥ 1,500/mcL * hemoglobin ≥ 9 g/dL without transfusion within 7 days of treatment * platelets ≥ 100,000/mcL * total bilirubin ≤ 2x upper limit of normal (ULN) * AST(SGOT)/ALT(SGPT) ≤ 2.5x institutional ULN or ≤ 5x ULN for those with liver metastases * serum creatinine ≤ 1.5x ULN OR * creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above 1.5x ULN * coagulation profile INR ≤ 1.5x ULN unless the participant is receiving an anticoagulant * triglyceride level \< 500 mg/dL or \< 5.7 mmol/L * cholesterol level \< 400 mg/dL or \< 10.34 mmol/L * Baseline tumor measurements must be documented from imaging within 28 days prior to study registration. Other non-laboratory tests must be performed within 28 days prior to study registration. * Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 14 days of study registration. Female subjects of childbearing potential should have a negative urine or serum pregnancy test repeated within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Female and male subjects of childbearing potential must agree to use an adequate method of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of tretinoin administration. Contraception is required before starting the first dose of study medication through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. There is a significant risk of fetal malformation if pregnancy occurs while on tretinoin at any dose level, even if for short exposure periods. * Be willing and able to provide written informed consent for the trial. Exclusion Criteria: * Metastatic disease impinging on the spinal cord or threatening spinal cord compression. Patients that have had previous treatment of disease with impinging on the cord with either surgery or radiotherapy with clinical or radiographic evidence of response or stability are eligible. * Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment), and have no evidence of new or enlarging brain metastases. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability, because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * Concurrent administration of other cancer specific therapy or investigational agents during the course of this study is not allowed. * Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. * Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. * Subjects who are pregnant, or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. Pregnant women are excluded from this study because tretinoin has the potential for teratogenic or abortifacient effects. Breastfeeding should be discontinued if the mother is treated on this protocol. Women who could potentially become pregnant while undergoing treatment on this protocol must be willing to use 2 methods of contraception.