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* Have previously completed or withdrawn from this study or any other study investigating pemetrexed.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.