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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01397305
• Date of registration: 25/05/2011
• Prospective Registration: No
• Primary sponsor: Isofol Medical AB
• Public title: An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate (Arfolitixorin) and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer
• Scientific title: An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer
• Date of first enrolment: April 14, 2011
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01397305
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Sweden

Contacts

• Name: Bengt G Gustavsson, PhD, MD
• Affiliation: Sahlgrenska University Hospital, Sweden

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Rectal Cancer

Intervention(s)

Drug: Pemetrexed

Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin)

Primary Outcome(s)

Feasibility of Pemetrexed Prior to Surgery [Time Frame: 3 cycles (21-day cycles)]

Secondary Outcome(s)

Correlation between 5,10-methylenetetrahydrofolate and HCy levels in blood [Time Frame: Samples taken prior before study treatment, during 3 cycles of chemotherapy and after completion of study treatment. Expected average 20 weeks.]

Number of Participants Receiving Sphincter Saving Surgery [Time Frame: Surgery following 3 cycles (21-day cycles) of chemotherapy]

[6R] 5,10-methylenetetrahydrofolate tissue concentration determination [Time Frame: Surgery following 3 cycles (21-day cycles) of chemotherapy]

Pathological Complete Response (pCR) [Time Frame: Surgery following 3 cycles (21-day cycles) of chemotherapy]

Pharmacokinetic parameters of [6R] 5,10-mTHF, 5-formyl-THF, 5-methyl-THF and THF calculated from plasma [Time Frame: Calculated on Day1 and Day15 after cycle 1 and 3]

Correlation of folate gene polymorphisms and gene signature profiling with clinical outcome and toxicity profiles. [Time Frame: Tissue to be collected from tumor and adjacent mucosa before start of study treatment, during and after completed study treatment. Expected average 20 weeks.]

Evaluation of qualitative and quantitative toxicities [Time Frame: Start of study treatment until last postoperative visit. Expected average 16 weeks.]

Secondary ID(s)

ISO-MC-091

Source(s) of Monetary Support

Please refer to primary and secondary sponsors