Dose Escalating Study of Foxy-5 in Breast-, Colon- or Prostate Cancer Patients

NCT02655952 | Completed Phase 1 DMC

• 1 other identifier: SMR-3164
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 4

Brief Summary

The Wnt proteins belong to a family of proteins that have been demonstrated to play a role in the formation and dissemination of tumours. The present project focuses on the critical role of the Wnt-5a protein in the pathobiological processes that lead to metastatic cancer disease. WntResearch has identified a formylated 6 amino acid peptide fragment, named Foxy-5, which mimick the effects of Wnt-5a to impair migration of epithelial cancer cells and thereby acting anti-metastatic. The aim of the first clinical phase I study was to establish the recommended dose for a clinical phase II study and enable further development of Foxy-5 as a first in class anti-metastatic cancer drug. The study did not see any DLTs and therefore failed to reach maximum tolerated dose (MTD); no recommended phase II dose (RP2D) could therefore be established based on toxicity. The aim of this study is to continue to establish the safety profile of Foxy-5 in higher doses, and determine the RP2D for later stage development based on any observed DLT's/MTD and further analysis of the pharmacodynamic profile of Foxy-5 to determine the biological response dose (BRD).

Conditions

Metastatic Breast Cancer; Metastatic Colon Cancer; Metastatic Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Presence of Dose Limiting Toxicities (DLTs).

  The number of adverse events along with the results of vital sign measurements, physical examinations, and clinical laboratory tests will be used to determine the safety and tolerability profile of Foxy-5

  6 month

Secondary Outcomes (12)

• Genome wide mRNA gene expression in tumour biopsies and blood (buffy coat)

  Tumour biopsies obtained prior to day 1 and on day 12 and 19

• Wnt-5a protein expression and hematoxylin-eosin (HE) staining of tumour biopsies

  Tumour biopsies obtained prior to day 1 and on day 12 and 19

• Numbers of circulating tumour cells (CTCs) in blood

  Blood sample obtained prior to day 1 and on day 12 and 19

• Maximum tolerated dose (MTD)

  6 month

• Area under the plasma concentration curve (AUC) of Foxy-5

  immediately prior to treatment, at 0, 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion.

Study Arms (1)

Foxy-5

EXPERIMENTAL

Slow infusion of lyophilised and reconstituted Foxy-5 three times weekly for three weeks. There will be a maximum of 8 dose cohorts. Cohorts 1-4 will be conducted in the United Kingdom and Denmark whereas cohorts 5-8 will only be conducted in Denmark. As doses in cohort 1 and 2 have been investigated in the previous phase I study, cohorts 1+2 and 3 can be run in parallel with dose escalation approved by the DSMB at all times. DK+UK: Cohort 1: 0.8 mg/kg DK+UK: Cohort 2: 1.3 mg/kg DK+UK: Cohort 3: 1.8 mg/kg DK+UK: Cohort 4: 2.3 mg/kg DK only: Cohort 5: 3.0 mg/kg DK only: Cohort 6: 4.0 mg/kg DK only: Cohort 7: 5.3 mg/kg DK only: Cohort 8: 7.0 mg/kg

Drug: Foxy-5

Interventions

Foxy-5 DRUG

Foxy-5

Eligibility Criteria

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

You may qualify if:

• Males and females of at least 18 years of age
• Histologically/cytologically documented diagnosis of metastatic breast, colon or prostate cancer, refractory to standard therapy or for which no curative therapy exists
• Must have an evaluable tumour appropriate for biopsy as determined by the Investigator.
• Loss of or reduced Wnt-5a protein expression in primary or metastatic tumour cells, characterised by IHC analysis
• Eastern Cooperative Oncology Group (ECOG) performance status of \<= 1
• Life expectancy of at least 3 months
• Unresectable disease, i.e. the metastases cannot be surgically removed with a curative intent
• weeks must have elapsed since the patient has received any other IMP
• weeks must have elapsed since the patient has received any anti cancer treatment; including radiotherapy (except for single dose of palliative radiotherapy), cytotoxic chemotherapy, biologic agents or targeted therapy
• weeks must have elapsed since any prior surgery or therapy with bone marrow stimulating factors
• Adequate haematological functions as defined by:
• Absolute neutrophil count \>= 1.5 10E9/L
• Platelets \>= 100 10E9/L
• Hemoglobin \>= 5.6 mmol/L
• Adequate hepatic function as defined by:

You may not qualify if:

• Active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease)
• Any active infection requiring antibiotic treatment
• Known infection with human immunodeficiency virus (HIV) or hepatitis virus
• Active heart disease including myocardial infarction or congestive heart failure within the previous 6 months, symptomatic coronary artery disease, or symptomatic arrhythmias currently requiring medication
• Known or suspected active central nervous system (CNS) metastasis. (Patients stable 8 weeks after completion of treatment for CNS metastasis are eligible)
• Impending or symptomatic spinal cord compression or carcinomatous meningitis
• Requiring immediate palliative surgery and/or radiotherapy(except for a single dose of palliative radiotherapy)
• Pre-existing neuropathy, i.e., Grade \>2 neuromotor or neurosensory toxicity
• Participation in other clinical studies within 4 weeks of first dose of study treatment
• Previous exposure to Foxy-5
• History of severe allergic or hypersensitive reactions to excipients
• Pregnant or breastfeeding women
• Active and/or within the last 5 years histologically confirmed diagnosis of malignant melanoma, gastric cancer, pancreatic cancer, lung cancer or nasopharyngeal cancer
• Severe or uncontrolled chronic or uncontrolled systemic disease (e. g. severe respiratory or cardiovascular disease)
• Other medications or conditions that in the Investigator's opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results

Sponsors & Collaborators

• WntResearch AB: lead

Study Sites (4)

Clinical Research Department, Oncology, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Onkologisk Afdeling R, Herlev Hospital

Herlev, 2730, Denmark

Location

Odense University Hospital

Odense, Denmark

Location

NCCC, Freeman Hospital

Newcastle, Newcastle Upon Tyne, NE7 7DN, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms; Colonic Neoplasms; Prostatic Neoplasms

Interventions

Foxy-5 peptide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Tine Mølvadgaard, M.Sc.Pharm

  Smerud Medical Research Denmark

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 14, 2016
• Study Start: April 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: December 28, 2018

Record last verified: 2018-02

Locations

DK (3); GB (1)