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

• ClinicalTrials.gov Identifier: NCT03883802
• Recruitment Status: Active, not recruiting
• First Posted: March 21, 2019
• Last Update Posted: December 9, 2022
• Sponsor: WntResearch AB
• Collaborators: SMS-Oncology BV; SAGA diagnostics AB; Unilabs A/S; BioVica AB; Institut Català d'Oncologia
• Information provided by (Responsible Party): WntResearch AB

Tracking Information

• First Submitted Date: December 26, 2018
• First Posted Date: March 21, 2019
• Last Update Posted Date: December 9, 2022
• Actual Study Start Date: April 12, 2019
• Estimated Primary Completion Date: December 14, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 20, 2019)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: From date of randomization until 28 days after the last dose of Foxy-5, assessed up to 120 days ]
  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.
• ctDNA as surrogate marker for disease free period [ Time Frame: 2 years after resection of colon cancer ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 20, 2019)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: March 20, 2019)

Thymidine Kinase activity [ Time Frame: 1 year after resection of tumour ]

The level of thymidine kinase activity in serum in relationship to Wnt- 5a expression in the tumour.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Foxy-5 as Neo-Adjuvant Therapy in Subjects With Wnt-5a Low Colon Cancer
• Official Title: A Randomized, Multicentre, Open-Label Controlled Phase II Trial of Foxy-5 as Neo-Adjuvant Therapy in Subjects With Wnt-5a Low Colon Cancer
• Brief Summary: 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.

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
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

two-arm study, 1 to 1 randomization: treatment group and standard therapy

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Colon Cancer

Intervention

• 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

Study Arms

• 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
  Interventions:

  • Drug: Foxy-5
  • Drug: FOLFOX regimen
  • Procedure: Tumour resection (colon cancer surgery)
• Active Comparator: Standard therapy
  Surgical removal of tumour followed by 6 months FOLFOX regimen
  Interventions:

  • Drug: FOLFOX regimen
  • Procedure: Tumour resection (colon cancer surgery)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: March 20, 2019): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 14, 2024
• Estimated Primary Completion Date: December 14, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT03883802
• Other Study ID Numbers: SMS-0472B; 2018-003074-27 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: WntResearch AB
• Original Responsible Party: Same as current
• Current Study Sponsor: WntResearch AB
• Original Study Sponsor: Same as current

Collaborators

• SMS-Oncology BV
• SAGA diagnostics AB
• Unilabs A/S
• BioVica AB
• Institut Català d'Oncologia

Investigators

• Principal Investigator: Ramon Salazar, MD; Institut Català d'Oncologia

• PRS Account: WntResearch AB
• Verification Date: December 2022