An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate (Arfolitixorin) and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer

Inclusion Criteria: * Pathological/ cytological diagnosis of adenocarcinoma of the rectum. Patients must have operable rectal cancer that is amenable to surgery. * No prior therapy for rectal cancer * Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1 * Adequate organ function * Patient compliance and geographic proximity that allow adequate follow-up * For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after treatment; must have a negative serum or urine pregnancy test and must not be lactating. * For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after treatment. * Estimated life expectancy of at least 12 weeks * Signed informed consent * At least 18 years of age Exclusion Criteria: * Concurrent administration of any other anti-tumor therapy. * Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. * Serious concomitant systemic disorders (e.g., active infection including HIV, cardiac disease) that in the opinion of the investigator would compromise the patient's ability to complete the study. * Have previously completed or withdrawn from this study or any other study investigating pemetrexed. * Are pregnant or breast-feeding. * Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. * History of significant neurological or mental disorder, including seizures or dementia. * Inability to interrupt aspirin or other nonsteroidal anto-inflammatory drugs (NSAIDs) * Presence of clinically relevant third-space fluid collection that cannot be controlled by drainage or other procedures prior to study entry. * Inability or unwillingness to be given 5,10-methylenetetrahydrofolate, vitamin B12 or dexamethasone.