Intervention: Capecitabine
Trial phase: Phase 2
ATC code: L01BC06
SMILES: CCCCCOC(=O)Nc1nc(=O)n([C@@H]2O[C@H](C)[C@@H](O)[C@H]2O)cc1F
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 2
Group description: Participants are to receive 500 mg/m² of capecitabine orally (PO) twice daily (BID) on days 1 to 14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 2 years.
Eligibility criteria:
INCLUSION CRITERIA

Squamous cell carcinoma of the skin or "unknown primary lesions" at the time of diagnosis if metastatic disease present with a history of plausible primary skin site removed in the past. Example: squamous cell carcinoma in neck or parotid lymph nodes with no identifiable mucosal primary but with a history of the removal of one or more early stage squamous cell carcinomas of the skin in an anatomically relevant lymphatic drainage region would be eligible
Measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension as ≥ 10 mm with computed tomography (CT) scan; magnetic resonance imaging (MRI); or calipers during clinical exam
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
Life expectancy greater than 3 months
Absolute neutrophil count ≥ 1,000/mcL
Platelets ≥ 100,000/mcL

Total bilirubin

Within normal institutional limits OR
≤ 2 x upper limit of normal (ULN) if participant has Gilbert's syndrome (elevated unconjugated bilirubin from decreased UDP glucuronosyltransferase 1 family, polypeptide A1 [UGT1A1] activity)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional ULN or up to 5 X ULN if known to be caused by liver metastases

Creatinine OR

< 1.3 mg/dL OR
Creatinine clearance ≥ 30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (Note creatinine clearances between 30 and 49 mg/dL necessitate dose modification)
For participants with a history of coronary artery disease (CAD)/myocardial infarction (MI) or congestive heart failure (CHF), ejection fraction (EF) ≥ 50% by multi-gated acquisition (MUGA) or echocardiogram (exceptions by PI discretion)

EXCLUSION CRITERIA

Prior treatment with systemic capecitabine or prodrugs
Prior treatment with systemic fluorouracil (5-FU) or prodrugs (prior topical treatment with 5FU is permitted if recovered from any toxicities > grade 1, and after at least 5 half-lives of the last systemically administered agent have passed)
Receiving any other investigational agents or anti-cancer treatments
Candidates for curative locoregional treatment (patients with recurrent locoregional disease following surgery and/ or radiation for which a resection is unacceptably morbid and unlikely to be curative are eligible)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine

Uncontrolled concurrent illness including, but not limited to:

Ongoing or active infection
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmia
Psychiatric illness/social situations that would limit compliance with study requirements
Pregnant
Lactating