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

This study is currently recruiting participants.
Verified December 2016 by WntResearch AB
Sponsor:
ClinicalTrials.gov Identifier:
NCT02655952
First Posted: January 14, 2016
Last Update Posted: January 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
WntResearch AB
  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 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).


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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Dose Escalating Study to Evaluate the Safety, Tolerability and Pharmacodynamic Response of Foxy-5 in Patients With Metastatic Breast-, Colon- or Prostate Cancer

Resource links provided by NLM:


Further study details as provided by WntResearch AB:

Primary Outcome Measures:
  • Presence of Dose Limiting Toxicities (DLTs). [ Time Frame: 6 month ]
    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


Secondary Outcome Measures:
  • Genome wide mRNA gene expression in tumour biopsies and blood (buffy coat) [ Time Frame: Tumour biopsies obtained prior to day 1 and on day 12 and 19 ]
    Determination of the biological response dose (BRD) based on the alterations in the exploratory biomarkers during treatment with Foxy-5

  • Wnt-5a protein expression and hematoxylin-eosin (HE) staining of tumour biopsies [ Time Frame: Tumour biopsies obtained prior to day 1 and on day 12 and 19 ]
    Determination of the biological response dose (BRD) based on the alterations in the exploratory biomarkers during treatment with Foxy-5

  • Numbers of circulating tumour cells (CTCs) in blood [ Time Frame: Blood sample obtained prior to day 1 and on day 12 and 19 ]
    Determination of the biological response dose (BRD) based on the alterations in the exploratory biomarkers during treatment with Foxy-5

  • Maximum tolerated dose (MTD) [ Time Frame: 6 month ]
    Determined as the dose preceding the dose at which two or more patients have experienced DLTs. Assessment of adverse events and laboratory abnormalities

  • Area under the plasma concentration curve (AUC) of Foxy-5 [ Time Frame: immediately prior to treatment, at 0, 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion. ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

  • Bioavailability (F) of Foxy-5 [ Time Frame: immediately prior to treatment, at 0, 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion. ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

  • Half life (T½) of Foxy-5 [ Time Frame: immediately prior to treatment, at 0, 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion. ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

  • Absorption rate Constant (tmax) of Foxy-5 [ Time Frame: immediately prior to treatment, at 0, 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion. ]
    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: immediately prior to treatment, at 0, 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion. ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

  • Clearance (C) of Foxy-5 [ Time Frame: immediately prior to treatment, at 0, 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion. ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

  • Extraction Ratio (E) of Foxy-5 [ Time Frame: immediately prior to treatment, at 0, 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion. ]
    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

  • Hepatic and Renal Clearance of Foxy-5 [ Time Frame: immediately prior to treatment, at 0, 5, 15, 30, minutes 1, 3, 6, 8, 24, 48, 72 and 96 hours after infusion. ]
    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: 15
Study Start Date: April 2016
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Foxy-5

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

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

      • 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)
    • Aspartate aminotransferase (AST) <= 2.5 x ULN*
    • Alanine aminotransferase (ALT) <= 2.5 x ULN*

      • For patients with liver metastasis adequate hepatic function is defined by AST <= 5 x ULN and ALT <= 5 ULN.
    • Adequate renal function as defined by Serum creatinine <= 1,5 x ULN
    • Patients in active anti-coagulating treatment must be evaluated according to local standards on the discretion of the Investigator..
    • 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(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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02655952


Contacts
Contact: Peter G. Sørensen, MD +45 3868 9044 peter.grundtvig.soerensen@regionh.dk
Contact: Tine Mølvadgaard, M.Sc.Pharm +45 2066 2199 Tine.Molvadgaard@smerud.com

Locations
Denmark
Clinical Research Department, Oncology, Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Morten M Sørensen    +45 35450879    mms@regionh.dk   
Onkologisk Afdeling R, Herlev Hospital Recruiting
Herlev, Denmark, 2730
Contact: Peter G. Sørensen    +45 38689044    petyer.grundtvig.soerensen@regionh.dk   
Odense University Hospital Recruiting
Odense, Denmark
Contact: Camilla Quortrup    +45 51428359    camilla.quortrup@rsyd.dk   
United Kingdom
NCCC, Freeman Hospital Recruiting
Newcastle, Newcastle upon Tyne, United Kingdom, NE7 7DN
Contact: Ruth Plummer       ruth.plummer@newcastle.ac.uk   
Sponsors and Collaborators
WntResearch AB
Investigators
Study Director: Tine Mølvadgaard, M.Sc.Pharm Smerud Medical Research Denmark
  More Information

Responsible Party: WntResearch AB
ClinicalTrials.gov Identifier: NCT02655952     History of Changes
Other Study ID Numbers: SMR-3164
First Submitted: January 6, 2016
First Posted: January 14, 2016
Last Update Posted: January 5, 2017
Last Verified: December 2016

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases