E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with resectable adenocarcinoma of the colon and who, at the time of screening, are considered to fulfil the local criteria for adjuvant post-operative chemotherapy. Based on CT/MRI subjects should be judged to be: T1-4, N1-2, M0 or T4, N0, M0. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of Foxy-5 in subjects with colon cancer. To assess circulating tumour DNA (ctDNA) in plasma as a surrogate parameter for disease recurrences in subjects with Wnt-5a low colon cancer treated with Foxy-5 compared to subjects with Wnt-5a low colon cancer who are in the Control Arm. |
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E.2.2 | Secondary objectives of the trial |
To determine the preliminary efficacy of Foxy-5 in subjects with colon cancer by assessing: • Overall survival (OS) defined as the time of surgery until death due to any cause, assessed at two years after surgery. • Disease-free survival (DFS) defined as the time from surgery to tumour recurrence or death due to any cause, assessed at two years after surgery. • Recurrence-free interval (RFI) defined as the time from randomization to tumour recurrence. • Circulating tumour DNA (ctDNA) in plasma as a surrogate parameter for disease recurrences in subjects with Wnt-5a high colon cancer treated with Foxy-5 compared to subject with Wnt-5a high colon cancer who are in the Control Arm.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ability to understand and willingness to provide written informed consent before any trial-related activities. 2. Age ≥ 18 years. 3. Male or female subjects with adenocarcinoma of the colon, judged by CT or MRI as either one of the following stages per TNM classification of colon cancer (8th edition, 2017): T1-4, N1-2, M0 or T4, N0, M0 and who are considered to fulfil the local criteria for adjuvant post-operative chemotherapy after scheduled surgery. 4. Scheduling of surgery according to local practice allows at least 9 pre-surgery administrations of Foxy-5 for the subject. (Please note: surgery should not be postponed for trial treatments). 5. Sexually active women of childbearing potential (WOCBP) and males with WOCBP partners who are randomized to the Foxy-5 Arm must use a highly effective method of contraception for the treatment duration and for 28 days after last Foxy-5. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 7. Clinical laboratory values at screening: a. Absolute neutrophil count ≥1.5 x 109/L b. Haemoglobin ≥ 9 g/dL c. Platelets ≥ 100 x 109/L d. Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤1.5x Upper Limit of Normal (ULN) e. Serum bilirubin ≤1.5 x the ULN f. Creatinine clearance >60 mL/min (determined by Cockcroft-Gault Equation).
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E.4 | Principal exclusion criteria |
1. Assessed as not suitable or unable to tolerate adjuvant chemotherapy. 2. Evidence of distant metastatic (M1) disease at Screening (N1-2 is allowed). 3. Any surgery (except tumour biopsy) or therapy with immune suppressive agents or bone marrow stimulating factors within the last two weeks prior to randomization. 4. Any active infection requiring IV antibiotic treatment at the time of screening. 5. History of hematologic or primary solid tumour malignancy. Subjects in complete remission for at least 5 years or judged as cured by the Investigator may be included. Subjects with any prior non-invasive basal and squamous skin cell carcinoma, cervical carcinoma of Stage 1B or less, and non-invasive superficial bladder cancer may be included. 6. Pregnant or breastfeeding women. 7. Currently participating in another trial and receiving trial therapy or received investigational therapy within 4 weeks of the first dose of Foxy-5. 8. Any other condition or treatment that, in the opinion of the Investigator, might interfere with the trial or current drug or substance abuse. 9. Inability to understand the protocol requirements, instructions and trial-related restrictions, the nature, scope, and possible consequences of the trial. 10. Unlikely to comply with the protocol requirements, instructions and trial-related restrictions; e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the trial 11. Legal incapacity or limited legal capacity. 12. Any condition, which results in an undue risk for the subject during the trial participation according to the Investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
1) The incidence of adverse events (AEs) related to Foxy-5 administration and Grade 3 and higher according to the National Cancer Institute – Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) and the Clavien-Dindo classification of surgical complications. 2) The level of ctDNA in plasma of subjects with Wnt-5a low colon cancer as a surrogate parameter for disease recurrence in subjects with Wnt-5a low colon cancer treated with Foxy-5 compared to subjects with Wnt-5a low colon cancer who are in the Control Arm.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Ongoing during the trial and after administration of Foxy-5 is completed for all subjects 2) Ongoing during the trial until 2 years after resection of the colon cancer and after follow-up period is completed for all subjects |
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E.5.2 | Secondary end point(s) |
1) OS at 2 years after resection of the colon cancer; 2) DFS at 2 years after resection of the colon cancer; 3) RFI 4) The level of ctDNA in plasma of subjects with Wnt-5a high colon cancer.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
If not otherwise specified in section E.5.2, ongoing during the trial and after follow-up period is completed for all subjects |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |