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

NCT01681472 | Completed Phase 1 Results

• 2 other identifiers: ISO-CC-0022012-000522-22
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Colonic Neoplasms

Keywords

Colon cancer; 5,10-methylenetetrahydrofolate; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Therapeutic Uses; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (8)

• Concentration of [6R]-5,10-methylene-THF in Tumor Tissue

  Comparison of concentration of the active substance in Modufolin: \[6R\]-5,10-methylene-THF in tumor tissue after the different treatments.

  Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration

• Concentration of [6R]-5,10-methylene-THF in Adjacent Mucosa Tissue

  Comparison of concentration of the active substance in Modufolin: \[6R\]-5,10-methylene-THF in mucosa adjacent to the tumor after the different treatments.

  Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration

• Concentration of [6S]-5-THF in Tumor Tissue

  Comparison of concentration of the metabolite \[6S\]-5-THF in tumor after the different treatments.

  Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration

• Concentration of [6S]-5-THF in Adjacent Mucosa Tissue

  Comparison of concentration of the metabolite \[6S\]-5-THF in mucosa adjacent to the tumor after the different treatments.

  Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration

• Concentration of [6S]-5-methyl-THF in Tumor Tissue

  Comparison of concentration of the metabolite \[6S\]-5-methyl-THF in tumor after the different treatments.

  Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration

• Concentration of [6S]-5-methyl-THF in Adjacent Mucosa Tissue

  Comparison of concentration of the metabolite \[6S\]-5-methyl-THF in mucosa adjacent to the tumor after the different treatments.

  Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration

• Concentration of [6S]-5-formyl-THF in Tumor Tissue

  Comparison of concentration of the metabolite \[6S\]-5-formyl-THF in tumor after the different treatments.

  Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration

• Concentration of [6S]-5-formyl-THF in Adjacent Mucosa Tissue

  Comparison of concentration of the metabolite \[6S\]-5-formyl-THF in mucosa adjacent to the tumor after the different treatments.

  Sample taken Day 1 (Day of surgery) at 0 min (before anesthetics) and 5, 10, 20, 40, 60, 90, 120, 180, 240, 360 min after study drug administration, and 24 h after study drug administration

Secondary Outcomes (35)

• AUC(0-2h) of [6R]-5,10-methylene-THF

  Samples taken Day 1 (Day of surgery)

• AUC(0-2h) of [6S]-5-THF

  Samples taken Day 1 (Day of surgery)

• AUC(0-2h) of [6S]-5-methyl-THF

  Samples taken Day 1 (Day of surgery)

• AUC(0-2h) of [6SR]-5-formyl-THF

  Samples taken Day 1 (Day of surgery)

• AUC(Last) of [6R]-5,10-methylene-THF

  Samples taken Day 1 (Day of surgery) and Day 2

Study Arms (4)

Levoleucovorin 200 mg/m2

ACTIVE COMPARATOR

One i.v. bolus injection of study drug after the patient has been anaesthetized.

Drug: Levoleucovorin 200 mg/m2

Levoleucovorin 60 mg/m2

ACTIVE COMPARATOR

One i.v. bolus injection of study drug after the patient has been anaesthetized.

Drug: Levoleucovorin 60 mg/m2

6R-MTHF 200 mg/m2

EXPERIMENTAL

One i.v. bolus injection of study drug after the patient has been anaesthetized.

Drug: 6R-MTHF (arfolitixorin) 200 mg/m2

6R-MTHF 60 mg/m2

EXPERIMENTAL

One i.v. bolus injection of study drug after the patient has been anaesthetized.

Drug: 6R-MTHF (arfolitixorin) 60 mg/m2

Interventions

6R-MTHF (arfolitixorin) 200 mg/m2 DRUG

i.v. bolus injection

Also known as: Modufolin®, ISO-901, [6R] 5,10-methylenetetrahydrofolate, arfolitixorin

6R-MTHF 200 mg/m2

Levoleucovorin 200 mg/m2 DRUG

i.v. bolus injection

Also known as: Isovorin®

Levoleucovorin 200 mg/m2

6R-MTHF (arfolitixorin) 60 mg/m2 DRUG

i.v. bolus injection

Also known as: Modufolin®, ISO-901, [6R] 5,10-methylenetetrahydrofolate, arfolitixorin

6R-MTHF 60 mg/m2

Levoleucovorin 60 mg/m2 DRUG

i.v. bolus injection

Also known as: Isovorin®

Levoleucovorin 60 mg/m2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Isofol Medical AB: lead

Study Sites (1)

Sahlgrenska University Hospital

Gothenburg, 461 85, Sweden

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases

Interventions

5,10-methylenetetrahydrofolic acid; Levoleucovorin; Leucovorin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Anders Rabbe
• Organization: Isofol Medical

anders.rabbe@isofolmedical.com

+46 (0)707 64 65 00

Study Officials

• Kristoffer Derwinger, MD PhD

  Sahlgrenska University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2012
• First Posted: September 10, 2012
• Study Start: September 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: September 25, 2020
• Results First Posted: July 17, 2015

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)