An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate (Arfolitixorin) and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer
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|ClinicalTrials.gov Identifier: NCT01397305|
Recruitment Status : Completed
First Posted : July 19, 2011
Last Update Posted : September 9, 2020
|Condition or disease||Intervention/treatment||Phase|
|Rectal Cancer||Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin) Drug: Pemetrexed||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Extended Feasibility Phase I/II Study of Methylenetetrahydrofolate and Pemetrexed Single Agent, Given as Neoadjuvant Treatment in Patients With Resectable Rectal Cancer|
|Actual Study Start Date :||April 14, 2011|
|Actual Primary Completion Date :||October 16, 2014|
|Actual Study Completion Date :||October 16, 2014|
Experimental: Modufolin and Pemetrexed
Modufolin ( [6R] 5,10-methylenetetrahydrofolate) and Pemetrexed
Drug: [6R] 5,10-methylenetetrahydrofolate (arfolitixorin)
10, 50, 100, 200, and 500 mg/m2 IV on day 1, day 8 day and day 15 of each 21-day cycle. 3 cycles.
500 mg/m2 IV on day 1 of each 21-day cycle. 3 cycles.
- Feasibility of Pemetrexed Prior to Surgery [ Time Frame: 3 cycles (21-day cycles) ]
Feasibility is defined as the ability to receive the total planned dose of pemetrexed (i.e., 1500 mg/m) administered over a period of no more than 9 weeks. Feasibility is measured as absence of the following toxicities:
- CTC grade 4 lasting >= 7 days, or febrile neutropenia
- CTC grade 4 thrombocytopenia or grade 3 with bleeding.
- CTC grade 3 nonhematologic toxicity (excluding nausea and vomiting, isolated CTC grade 3 ALT or AST that returns to the patient's pretreatment CTC grade within 3 weeks, or grade 3 fatigue lasting <7 days).
- Pathological Complete Response (pCR) [ Time Frame: Surgery following 3 cycles (21-day cycles) of chemotherapy ]
- Number of Participants Receiving Sphincter Saving Surgery [ Time Frame: Surgery following 3 cycles (21-day cycles) of chemotherapy ]
- Evaluation of qualitative and quantitative toxicities [ Time Frame: Start of study treatment until last postoperative visit. Expected average 16 weeks. ]Bleeding, anastomosis, leakage, serious infection.
- [6R] 5,10-methylenetetrahydrofolate tissue concentration determination [ Time Frame: Surgery following 3 cycles (21-day cycles) of chemotherapy ]
- 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. ]Blood samples are taken before start of study treatment, in conjunction with start of every study drug cycle, and after completed study treatment. HCy measurements performed using HPLC. 5-10-methylenetetrahydrofolate is measured in tissue biopsies (tumor and adjacent mucosa) sampled in conjunction with surgery. The tissue is collected before start of study treatment, during and after completed study treatment. 5,10-methylenetetrahydrofolate levels are measured using LC/MS/MS.
- 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. ]RT-PCR will be used to measure and determine the gene expression levels of the genes FPGS (Folylpolyglutamate synthase) and GGH (Gamma-glutamyl hydrolase). This translational research will be compared with the clinical outcome and toxicity profiles of patients.
- 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 ]Plasma samples will be collected prior to study treatment, and at 10 minutes, 1, 2 and 4 hours after study treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01397305
|Sahlgrenska University Hospital|
|Göteborg, Sweden, 416 85|
|Principal Investigator:||Bengt G Gustavsson, PhD, MD||Sahlgrenska University Hospital, Sweden|