Modelle 001, TS-inhibition in Colorectal Liver Metastases Comparing Arfolitixorin and Calciumfolinate

NCT04126655 | Unknown Phase 1 DMC

• 1 other identifier: 2016-005052-25
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

A study that is blinded to the patient and the investigator where the combination of Arfolitixorin + 5-FU is compared to Calciumfolinate + 5-FU. The patients will be randomised and will receive the above described combination as IV bolus injections, peroperatively in conjuction with collection of the first tissue sample. A low dose (30 mg) and a high dose (120) mg of Arfolitixorin will be used in order to investigate the relation between dose of Arfolitixorin and TS-inhibition.

Conditions

Metastatic Colorectal Cancer

Keywords

Colorectal cancer,; Liver metastases; 5-FU; Arfolitixorin; Calciumfolinate; TS-inhibtion

Outcome Measures

Primary Outcomes (3)

• TS inhibition i tumour tissue

  The primary objective is to compare the TS-inhibtion capacity of the combination Arfolitixorin/5-FU in contrast to Calciumfolinate/5-FU in tumour, adjacent liver parenchyma and plasma in patients with liver metastases from colorectal cancer

  Biopsies will be collected during liver surgery

• TS inhibition in adjacent liver parenchyma

  The primary objective is to compare the TS-inhibtion capacity of the combination Arfolitixorin/5-FU in contrast to Calciumfolinate/5-FU in adjacent liver in patients with liver metastases from colorectal cancer

  Biopsies will be collected during live surgery

• TS inhibition in plasma

  The primary objective is to compare the TS-inhibtion capacity of the combination Arfolitixorin/5-FU in contrast to Calciumfolinate/5-FU in plasma in patients with liver metastases from colorectal cancer

  Blood samples will be collected according to a sampling schedule during 24 hours after the bolus injection.

Study Arms (2)

Arfolitixorin.

EXPERIMENTAL

Drug: Arfolitixorin Drug: 5-FU Per operative i.v. bolus injection of Arfolitixorin in combination with 5-FU

Drug: Arfolitixorin

Calciumfolinate.

ACTIVE COMPARATOR

Drug: Calciumfolinate Drug: 5-FU Per operative i.v. bolus injection of Calciumfolinate in combination with 5-FU

Drug: Arfolitixorin

Interventions

Arfolitixorin DRUG

Per operative administration of 5-FU with Arfolitixorin or Calciumfolinate

Also known as: Calciumfolinate

Arfolitixorin.; Calciumfolinate.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must sign an informed consent document.
• At least two liver metastases secondary to CRC. Patients must have removable metastases amenable to surgery.
• Performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG). Performance Status scale. (See Protocol Attachment 1.)
• For women: Must be surgically sterile, postmenopausal, or compliant with a contraceptive regimen during and for 3 months after treatment. Fertile women must have a negative serum or urine pregnancy test (within 7 days before enrolment) and must not be lactating.
• For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after treatment.
• Patient legally competent and able to communicate effectively with the study personnel as judged by the investigator.
• Patient likely to co-operate during the study.
• Patients must be at least 18 years of age.

You may not qualify if:

• Concurrent administration of any other anti-tumour therapy minimum 3 weeks before surgery according to clinical practise.
• \. Treatment within the last 30 days with a drug/device that has not received regulatory approval for any indication at the time of study entry.
• \. Any intake of medication, which could influence folate, and vitamin B12 status, within 30 days of surgery.
• \. 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.
• \. Second primary malignancy that is clinically detectable at the time of consideration for study enrollment.
• \. Patients with a high risk of postoperative liver failure due to advanced liver metastatic load.
• \. Pregnancy. 8. History of significant neurological or mental disorder, including seizures or dementia.
• \. Presence of clinically relevant (i.e., detectable by physical examination) third-space fluid collection (e.g., ascites, pleural effusion) that cannot be controlled by drainage or other procedures prior to study entry.
• \. Known hypersensitivity to 5-FU and or Calciumfolinate/Arfolitixorin.

Sponsors & Collaborators

• Vastra Gotaland Region: lead
• Isofol Medical AB: collaborator

Study Sites (1)

Sahlgrenska University Hospital

Gothenburg, 41345, Sweden

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Helena Taflin, MD, PhD

  Vastra Gotaland Region

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Helena Taflin, MD, PhD

CONTACT

+4631342100; helena.taflin@vgregion.se

Göran Carlsson, MD,PhD

CONTACT

+4633421000; ulf.goran.carlsson@vgregion.se

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Randomisation will be performed by a sealed envelope system. The randomisation envelopes are kept in a locked cabinet together with the randomisation list Two sets of code envelopes are prepared. The study personnel that will be responsible for study drug administration will have one set for the randomisation of patients and one set will be held by the investigator for emergency code breaking. The code envelopes are prepared for each patient and contain information about what treatment the patient should receive. The randomisation will be made by the study personnel responsible for the administration of the study drugs at the day of the surgery. The patients will be randomised in consecutive order. The date and time of randomisation should be recorded on the document followed by a signature of the person opening the envelope.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: A total of 30 patients will be included in the study and will be equally randomised in three steps. In the first phase, six patients will receive a reduced dose 5-FU; 250 mg / m², of which three patients will be randomized to additional Calciumfolinate and three patients will be randomized to additional Arfolitixorin. P When all six patients have been followed up in the context of visits consultation, a clinical safety evaluation (SE) of all AE, and SAE will be performed by two independent physicians If the responsible physicians finds that it is safe that the study will continue, we intend to increase the dose of 5-FU 500 mg / m, after which additional 12 patients will be included. After inclusion of 6 patients receiving 5-FU 500 mg /m² in combination with Arfolitixorin in the dose of 30mg/m2 a dose adjustment will take place and the last 12 patients will be randomised to either Calciumfolinate 60 mg/m2 or Arfolitixorin 120 /m2.

Study Record Dates

• First Submitted: October 4, 2019
• First Posted: October 15, 2019
• Study Start: February 5, 2020
• Primary Completion: October 1, 2021
• Study Completion: November 1, 2021
• Last Updated: August 27, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)