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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by WntResearch AB
Sponsor:
Information provided by (Responsible Party):
WntResearch AB
ClinicalTrials.gov Identifier:
NCT02020291
First received: December 11, 2013
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Colorectal Cancer
Prostate Cancer
Drug: Foxy-5
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Dose Escalating Study to Evaluate the Safety, Tolerability, Anti-Tumour Activity and Pharmacokinetic and Pharmacodynamic Profiles of Foxy-5 in Patients With Metastatic Breast, Colorectal or Prostate Cancer

Resource links provided by NLM:


Further study details as provided by WntResearch AB:

Primary Outcome Measures:
  • Safety and tolerability of Foxy-5 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Assessment of adverse events and laboratory abnormalities


Secondary Outcome Measures:
  • Profile for the biomarker NGAL and the amount of circulating tumour cells before and after treatment with Foxy-5 [ Time Frame: samples at pre-dose at day 1, pre-dose at day 12 and pre-dose at day 26 ] [ Designated as safety issue: No ]
  • Maximum tolerated dose (MTD) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

    To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of Foxy-5.

    Assessment of adverse events and laboratory abnormalities


  • Area under the plasma concentration curve (AUC) of Foxy-5 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS).

  • Maximum observed plasma drug concentration (Cmax) of Foxy-5 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS).

  • Time to maximum observed plasma drug concentration (tmax) of Foxy-5 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS).

  • Terminal elimination half-life (t½) of Foxy-5 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS).

  • Total plasma clearance (CL) of Foxy-5 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS).

  • Volume of distribution (V) of Foxy-5 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS).

  • Plasma concentration at steady state (Css) of Foxy-5 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS).

  • Drug accumulation ratio of Foxy-5 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS).


Estimated Enrollment: 27
Study Start Date: June 2013
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Foxy-5
One intravenous slow infusion of lyophilised and reconstituted Foxy-5 on day 1 (Monday), followed by a wash-out period of one week. During the subsequent weeks Foxy-5 will be administered as a slow infusion three times weekly on Monday, Wednesday and Friday for three weeks.
Drug: Foxy-5

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females of at least 18 years of age
  • Histologically/cytologically documented diagnosis of metastatic breast, colorectal 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 (for the first 3 dosing cohorts any protein expression of Wnt-5a is allowed and results are not needed before administration of study drug)
  • 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 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)
  • Aspartate aminotransferase (AST) <= 2.5 x ULN
  • Alanine aminotransferase (ALT) <= 2.5 x ULN
  • Adequate renal function as defined by Serum creatinine <= 1,5 x ULN
  • Provision of written informed consent
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
  • Sexually active males and females of child-producing potential, must use adequate contraception (intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release) or diaphragm always with spermicidal jelly and a male condom) for the study duration and at least six months afterwards

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02020291

Contacts
Contact: Peter G Sørensen, MD +45 38689044 Peter.Grundtvig.Soerensen@regionh.dk
Contact: Dorte Nielsen, MD Professor + 45 38682344 dorte.nielsen.01@regionh.dk

Locations
Denmark
Oncology Department, Herlev Hospital Recruiting
Herlev, Denmark, 2730
Contact: Peter G Sørensen, MD    +45 38689044    Peter.Grundtvig.Soerensen@regionh.dk   
Principal Investigator: Peter G Sørensen, MD         
Sponsors and Collaborators
WntResearch AB
  More Information

No publications provided

Responsible Party: WntResearch AB
ClinicalTrials.gov Identifier: NCT02020291     History of Changes
Other Study ID Numbers: SMR-2562
Study First Received: December 11, 2013
Last Updated: December 18, 2013
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Danish Health and Medicines Authority
Denmark: Ethics Committee

Keywords provided by WntResearch AB:
Foxy-5
Wnt-5A

Additional relevant MeSH terms:
Prostatic Neoplasms
Colorectal Neoplasms
Breast Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on October 19, 2014