Phase 2 N=32 Randomized Single-blind Treatment

PK/PD Investigation of Modufolin (Arfolitixorin) in Plasma, Tumor and Adjacent Mucosa Adjacent Mucosa in Patients With Colon Cancer

Colonic Neoplasms

Bottom Line

View on ClinicalTrials.gov: NCT01681472 ↗

Enrolled (actual)

Serious AEs

16.1%

Results posted

Jul 2015

Primary outcome: Primary: Concentration of [6R]-5,10-methylene-THF in Tumor Tissue — 1871; 959; 4725; 2393 pmol/g — p=0.0323

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: 6R-MTHF (arfolitixorin) 200 mg/m2 (Drug); Levoleucovorin 200 mg/m2 (Drug); 6R-MTHF (arfolitixorin) 60 mg/m2 (Drug); Levoleucovorin 60 mg/m2 (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Isofol Medical AB
Primary completion: Aug 2013

Outcome Measures

Outcome	Result	p-value
PRIMARY Concentration of [6R]-5,10-methylene-THF in Tumor Tissue	1871; 959; 4725; 2393	0.0323 sig
PRIMARY Concentration of [6R]-5,10-methylene-THF in Adjacent Mucosa Tissue	1333; 626; 5099; 3481	0.1480
PRIMARY Concentration of [6S]-5-THF in Tumor Tissue	1329; 933; 4175; 2219	0.1182
PRIMARY Concentration of [6S]-5-THF in Adjacent Mucosa Tissue	1333; 626; 5099; 3481	0.2716
PRIMARY Concentration of [6S]-5-methyl-THF in Tumor Tissue	3574; 1904; 4396; 1882	0.0092 sig
PRIMARY Concentration of [6S]-5-methyl-THF in Adjacent Mucosa Tissue	3667; 1216; 2494; 2066	0.0728
PRIMARY Concentration of [6S]-5-formyl-THF in Tumor Tissue	3611; 512; 100; 57	0.0728
PRIMARY Concentration of [6S]-5-formyl-THF in Adjacent Mucosa Tissue	5456; 1403; 82; 42	0.0240 sig
SECONDARY AUC(0-2h) of [6R]-5,10-methylene-THF	326.40261; 239.90076; 7734.09113; 0	—
SECONDARY AUC(0-2h) of [6S]-5-THF	827.1083; 640.0489; 19408.1712; 5639.2700	0.0015 sig
SECONDARY AUC(0-2h) of [6S]-5-methyl-THF	2336.24432; 1258.60184; 2277.89290; 997.74091	0.0728
SECONDARY AUC(0-2h) of [6SR]-5-formyl-THF	29911.9184; 7595.4599; 0; 0	—
SECONDARY AUC(Last) of [6R]-5,10-methylene-THF	462.10746; 239.90076; 7910.61038; 2272.78010	0.0015 sig
SECONDARY AUC(Last) of [6S]-5-THF	2231.1443; 640.0489; 28466.5389; 6766.9104	0.0015 sig
SECONDARY AUC(Last) of [6S]-5-methyl-THF	32206.2771; 7689.0921; 21737.2428; 5495.1924	0.0240 sig
SECONDARY AUC(Last) of [6S]-5-formyl-THF	43429.1885; 9637.0308; 75.6174; 50.1858	—
SECONDARY Cmax of [6R]-5,10-methylene-THF	195.0000; 123.0000; 22087.5000; 6452.8571	0.0014 sig
SECONDARY Cmax of [6S]-5-THF in Plasma	577.6250; 335.0000; 13372.5000; 5015.7143	0.0015 sig
SECONDARY Cmax of [6S]-5-methyl-THF in Plasma	2786.25000; 1078.00000; 2020.50000; 800.42857	0.0240 sig
SECONDARY Cmax of [6S]-5-formyl-THF in Plasma	32962.5000; 10168.3333; 252.7500; 261.0000	—
SECONDARY Tmax of [6R]-5,10-methylene-THF	1.14285857; 1.00000000; 0.08333000; 0.08333000	1.0000
SECONDARY Tmax of [6S]-5-THF	2.02083375; 1.50000000; 0.38541750; 0.09523571	0.0056 sig
SECONDARY Tmax of [6S]-5-methyl-THF	4.75000000; 2.41666667; 3.75000000; 2.92857143	0.1796
SECONDARY Tmax of [6S]-5-formyl-THF	0.12499750; 0.08333000; 0.10416500; 0.08333000	—
SECONDARY T(1/2) of [6R]-5,10-methylene-THF	3.07069184; 9.12204918; 0.90893994; 0.34368840	0.0268 sig
SECONDARY T(1/2) of [6S]-5-THF	5.59459251; 0; 1.24808943; 0.96378070	0.0177 sig
SECONDARY T(1/2) of [6S]-5-methyl-THF	7.0955575; 10.7281060; 9.0743346; 8.5121573	—
SECONDARY T(1/2) of [6S]-5-formyl-THF	1.51328500; 0.98944069; 0.23180085; 0	—
SECONDARY T(Last) of [6R]-5,10-methylene-THF	3.00000000; 2.00000000; 3.25000000; 1.35714286	0.0011 sig
SECONDARY T(Last) of [6S]-5-THF	4.75000000; 2.00000000; 5.75000000; 3.42857143	0.0015 sig
SECONDARY T(Last) of [6S]-5-methyl-THF	24.0000000; 12.0000000; 15.0000000; 8.5714286	0.1791
SECONDARY T(Last) of [6S]-5-formyl-THF	6.00000000; 8.33333333; 0.33333500; 0.16667000	—
SECONDARY Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6R]-5,10-methylene-THF	0.54039; NA; -0.21666; 0.68223; NA; 0.27618	0.6063
SECONDARY Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-THF	-0.02188; NA; 0.27018; 0.38298; 0.07937; NA	0.3964
SECONDARY Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-methyl-THF	0.73743; 0.44757; 0.03292; 0.09033; 0.76502; 0.34496	0.0586
SECONDARY Correlation Between Plasma and Tissue Concentration (Tumor and Mucosa) for [6S]-5-formyl-THF	0.68778; 0.11512; 0.23512; 0.02576	0.5751
SECONDARY Gene Expression Ratios (Mucosa:Tumor)	1.35; 5.60; 1.86; 3.33; 2.03; 2.75	0.0451 sig
SECONDARY Correlation of Gene Expression in Tumor and Adjacent Mucosa	-0.47193; -0.70730; 0.75404; 0.42972; 0.11497; 0.89976	0.3359
SECONDARY Homocystein Concentration	12.59; 11.27; 14.53; 13.80; 6.41; 6.40	—
SECONDARY S-Folate Concentration	21.75; 21.00; 15.03; 18.71; 45.00; 45.00	—
SECONDARY Change in Homocystein Concentration From Screening	5; 4; 4; 4; 0; 1	—
SECONDARY Change in S-Folate Concentration From Screening	7; 8; 5; 8; 0; 0	—
SECONDARY Number of AEs Per Severity	1; 0; 1; 5; 3; 0	—

Summary

The purpose of this study is to compare the concentration of four different metabolites in the tumor, in adjacent mucosa and in plasma in patients with colon cancer receiving two different doses of Modufolin (arfolitixorin) and Levoleucovorin (Isovorin®), respectively (60 and 200 mg/m2).

Eligibility Criteria

Main Inclusion Criteria:

Operable colon cancer amenable to curative surgery.
Performance status of 0 to 1
Informed consent form
Patients must be at least 18 years of age.

Main Exclusion Criteria:

Any concurrent other anti-tumor therapy
Any prohibited concomitant medication within 30 days of surgery
Pregnancy or breast-feeding.
Second primary malignancy

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01681472). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.