Phase I Study to Evaluate Safety, Tolerability, Anti-Tumour Activity and PK Profiles of Foxy-5 in Metastatic Breast, Colon or Prostate Cancer

NCT02020291 | Completed Phase 1 DMC

• 1 other identifier: SMR-2562
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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 present clinical phase 1 trial is to establish the recommended dose for a clinical phase 2 study and thereby further develop Foxy-5 as a first in class anti-metastatic cancer drug. Foxy-5 is designed to inhibit the development of metastasis by reducing the motility of cancer cells and should thereby increase the survival rates of patients with solid malignant tumours.

Conditions

Metastatic Breast Cancer; Colorectal Cancer; Prostate Cancer

Keywords

Foxy-5; Wnt-5A

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of Foxy-5

  Assessment of adverse events and laboratory abnormalities

  1 year

Secondary Outcomes (13)

• Profile for the biomarker NGAL and the amount of circulating tumour cells before and after treatment with Foxy-5

  samples at pre-dose at day 1, pre-dose at day 12 and pre-dose at day 26

• Profile for the biomarker 15-PGHD and the amount of circulating tumour cells before and after treatment with Foxy-5

  samples at pre-dose at day 1, pre-dose at day 12 and pre-dose at day 26

• Maximum tolerated dose (MTD)

  1 year

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

  Plasma immediately prior to treatment, instantly after infusion, at 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion. In the Multiple dosing cycles on days 1+3+5 and 15+29

• Maximum observed plasma drug concentration (Cmax) of Foxy-5

  Plasma immediately prior to treatment, instantly after infusion, at 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion. In the Multiple dosing cycles on days 1+3+5 and 15+29

Study Arms (1)

Foxy-5

EXPERIMENTAL

Slow infusion of lyophilised and reconstituted Foxy-5 three times weekly on Monday, Wednesday and Friday for three weeks.

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
• 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
• \>= 4 weeks must have elapsed since the patient has received any other IMP
• \>=4 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
• \>= 2 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:
• Total bilirubin \<= 1.5 x the upper limit of normal (ULN)

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
• 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
• History of severe allergic or hypersensitive reactions to excipients
• Pregnant or breastfeeding women
• Chronic immunosuppressant use (e.g. systemic steroids for treatment of autoimmune disease)
• History of second malignancy, including histologically confirmed diagnosis of malignant melanoma except for carcinoma in situ or basal cell carcinoma
• 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 (1)

Oncology Department, Herlev Hospital

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms; Prostatic Neoplasms

Interventions

Foxy-5 peptide

Condition Hierarchy (Ancestors)

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

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: December 11, 2013
• First Posted: December 24, 2013
• Study Start: June 1, 2013
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: February 2, 2016

Record last verified: 2016-02

Locations

DK (1)