Clinical Development

Clinical studies

The AGENT study

Isofol is now focused on the initiated Pivotal Phase 3 AGENT study (ISO-CC-007) which is currently recruiting patients in the USA, Canada and Europe. In total around 80 hospitals will participate in recruiting around 440 patients who will receive first line treatment for metastatic colorectal cancer (mCRC).

The study will have two treatment arms: the first group will be treated with arfolitixorin, and the second, with leucovorin (today’s folate-based treatment), both in combination with the 5-FU and oxaliplatin chemotherapeutic agents and the biological therapy, bevacizumab (Avastin), see illustration below.

The primary focus of the study will be to measure the percentage of patients who experience tumour size reduction, (Objective Response Rate, ORR). The secondary endpoint will be the measurement of Progression Free Survival (PFS), i.e. the time until the tumour begins to grow again or the patient dies. A ststistically significant tumour shrinkage in 55-60 % of patients should be demonstrated. Isofol’s objective is, therefore, to achieve a 10-15% improvement in ORR in those patients treated with arfolitixorin in comparison with those treated with leucovorin.

Interim analysis and final analysis

An interim analysis of ORR and PFS will be performed after 330 patients have been treated for at least 16 weeks. With a positive outcome for tumor reduction, ORR (an improvement of about 10 percentage points) in the interim analysis combined with a positive trend for survival, PFS, an independent group, a so-called Data Safety Monitoring Board (DSMB), may propose an extension of the study with another 220 patients (a total of 660 patients) to strengthen the statistical basis for evaluation of PFS. The interim analysis is now planned for the first half of 2020, but is dependent on the outcome of the patient recruitment. The entire study is expected to be completed during the first half of 2021 (at 440 patients) or at the end of 2021 (at 660 patients).

All clinical studies

NCT IDResearchPreclinPhase 1Phase 2Phase 3
Colorectal Cancer
03750786AGENT
ISO-CC-007, Phase III. Pivotal study with 440 patients undergoing first line treatment for metastatic colorectal cancer (mCRC). Clinical Trial >>
Ongoing
01681472ISO-CC-002, a Phase I/II Pharmacockinetics and pharmacodynamics clinical investigation of arfolitixorin (Modufolin®) in Plasma, Tumor and Adjacent Mucosa in Patients with Colon Cancer. Clinical Trial >>
Completed
01397305ISO-MC-091, Phase I/II Study where Pemetrexed is co-administered with arfolitixorin (Modufolin®) to newly diagnosed, non-cytostatically-treated patients with resectable Rectal Cancer. Clinical Trial >>
Completed
02244632ISO-CC-005, Phase I/II arfolitixorin (Modufolin®) in Combination with 5-Fluorouracil Alone or with Irinotecamn or Oxaliplatin ± bevacizumab in patients with colorectal cancer.
Ongoing
Osteosarcoma
02383901ISO-MTX-OB1, A Retrospective Non-intervention Study tto investigate how rescue treatment with folates in patients with osteosarcoma works in clinical context. Clinical Trial >>
Results available
01987102ISO-MTX-003, Phase I/II study intended to identify the arfolitixorin (Modufolin®) dose to be used in continued clinical development for in the osteosarcoma indication. Clinical Trial >>
Completed

CLINICAL STUDIES IN PHASE I/II FOR BOTH HDMTX RESCUE AND COLORECTAL CANCER

ISO-CC-002

ISO-CC-002 (NCT01681472) is a Phase I/II single-center, blinded, randomized, pharmacokinetic and pharmacodynamic investigation with two doses of arfolitixorin compared to levoleucovorin in tumor tissue, adjacent mucosa and plasma for patients with colon cancer admitted for resection of the colon. The study is completed.

ISO-MC-091

ISO-MC-091 (NCT01397305) is a Phase I/II single-center, open-label, feasibility extended study of pemetrexed single agent with arfolitixorin (Modufolin®) given to chemo-naïve patients with newly diagnosed operable rectal cancer. The study is currently ongoing but approaching completion and the last patient is undergoing treatment.

ISO-CC-005

ISO-CC-005 (NCT02244632) is a Phase I/II, multiple-center, open label study aiming to identify the safety and tolearability of a dose range of arfolitixorin (Modufolin®) in combination with the routine doses of 5-FU and irinotecan or oxaliplatin (with or without bevacizumab) in patients with colorectal cancer, stage IV. Patients are currently being enrolled in eight active sites in Europe. The results will be used to define the dose to be documented as efficacious in a blinded multicentre trial in patients with colon cancer, stage IV.

ISO-MTX-003

ISO-MTX-003 (NCT01987102) is a Phase I/II open-label, multicenter clinical trial designed to identify the arfolitixorin (Modufolin®) dose with most favorable safety prospect and confirmed ability to mitigate HDMTX induced toxicity during treatment of osteosarcoma patients. This is the first study in which HDMTX rescue with arfolitixorin (Modufolin®) is investigated. The study is completed.