Foxy-5 as Neo-Adjuvant Therapy in Subjects With Wnt-5a Low Colon Cancer (NeoFox)

A Randomized, Multicentre, Open-Label Controlled Phase II Trial of Foxy-5 as Neo-Adjuvant Therapy in Subjects With Wnt-5a Low Colon Cancer

Phase II study investigating the safety, tolerability and effect on disease reccurence of Foxy-5 as neo-adjuvant therapy in resected colon cancer patients treated with FOLFOX chemotherapy regimen. It is a two-arm study and patients will be randomised to receive either standard therapy (surgery + FOLFOX 6 months regimen) or standard therapy + neo-adjuvant administration of Foxy-5 prior to- and following surgery (maximum of 39 administrations) until initiation of FOLFOX therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: Foxy-5; Drug: FOLFOX regimen; Procedure: Tumour resection (colon cancer surgery)

Detailed Description

Foxy-5 is a synthetic hexapeptide with a formylated N-terminus, derived from the protein sequence of the Wnt-5a protein. Low/no expression levels of Wnt-5 protein in primary tumour cells have been correlated to high risk of recurrent metastatic disease and shortened survival in several different types of cancer patients, including colon cancer.

Current standard therapy involves surgical removal of the tumour followed by 6 months treatment with chemotherapy (FOLFOX). Foxy-5 is expected to decrease migration of cancer cells, in subjects with low/absent levels of Wnt-5a protein in their primary tumour and hence result in lower recurrence and a better overall survival. The trial intends to establish the safety and tolerability of Foxy-5 and to evaluate early signs of anti-metastatic activity in subjects with resectable colon cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Valencia, Spain, 46010
    • Instituto de Investigación Sanitaria INCLIVA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to understand and willingness to provide written informed consent before any trial-related activities.
2. 18 years of age or older.

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 purposes.)
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:

   1. Absolute neutrophil count ≥1.5 x 109/L
   2. Haemoglobin ≥ 9 g/dL
   3. Platelets ≥ 100 x 109/L

   4. Aspartate Transaminase (AST) and Alanine Transaminase (ALT)

      ≤1.5x Upper Limit of Normal (ULN)

   5. Serum bilirubin ≤1.5 x the ULN
   6. Creatinine clearance >60 mL/min (determined by Cockcroft-Gault Equation).

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.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Foxy-5; Arm will receive Foxy-5 as neo-adjuvant therapy prior to surgical removal of tumour and afterwards until initiation of FOLFOX 6 months regimen	Drug: Foxy-5; Lyophilized powder for solution for intravenous infusion; Drug: FOLFOX regimen; 6 months treatment regimen; Procedure: Tumour resection (colon cancer surgery); Surgical removal of patients colon cancer
Active Comparator: Standard therapy; Surgical removal of tumour followed by 6 months FOLFOX regimen	Drug: FOLFOX regimen; 6 months treatment regimen; Procedure: Tumour resection (colon cancer surgery); Surgical removal of patients colon cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The incidence of adverse events (AEs) related to Foxy-5 administration of 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. cancer.	From date of randomization until 28 days after the last dose of Foxy-5, assessed up to 120 days
ctDNA as surrogate marker for disease free period	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.	2 years after resection of colon cancer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	OS at 2 years after resection of the colon cancer	2 years after resection of tumour
Disease-Free Survival	DFS at 2 years after resection of the colon cancer	2 years after resection of tumour
Recurrence-Free Interval	Recurrence-free interval (RFI) defined as the time from randomization to tumour recurrence.	study start to 2 years after resection of tumour
ctDNA in Wnt-5a high patients	The level of ctDNA in plasma of subjects with Wnt-5a high colon cancer.	2 years after resection of tumour

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thymidine Kinase activity	The level of thymidine kinase activity in serum in relationship to Wnt- 5a expression in the tumour.	1 year after resection of tumour

Collaborators and Investigators

• Sponsor: WntResearch AB
• Collaborators: Institut Català d'Oncologia; SMS-Oncology BV; SAGA diagnostics AB; Unilabs A/S; BioVica AB
• Investigators: Principal Investigator: Ramon Salazar, MD, Institut Catala d'Oncologia

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2019
• Primary Completion (Anticipated): December 14, 2024
• Study Completion (Anticipated): December 14, 2024

Study Registration Dates

• First Submitted: December 26, 2018
• First Submitted That Met QC Criteria: March 20, 2019
• First Posted (Actual): March 21, 2019

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: SMS-0472B; 2018-003074-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No