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Metastatic Breast CancerPhase 1NCT02655952

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

A Phase 1 study testing Foxy-5 in people with Metastatic Breast Cancer and Metastatic Colon Cancer, run by WntResearch AB at 4 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Foxy-5
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
4 sitesin 2 countries
Study dates
Apr 2016to Oct 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

Denmark3 sites

  • Clinical Research Department, Oncology, Rigshospitalet

    Copenhagen, 2100

  • Onkologisk Afdeling R, Herlev Hospital

    Herlev, 2730

  • Odense University Hospital

    Odense

Other trials in Denmark

United Kingdom1 site

  • NCCC, Freeman Hospital

    Newcastle, Newcastle Upon Tyne, NE7 7DN

Other trials in United Kingdom

About this study

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

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).

Being tested
Foxy-5
Medical subject headings
Breast Neoplasms, Colonic Neoplasms, Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Foxy-5Drug

Study groups in NCT02655952
Study groupRoleWhat they receive
Foxy-5ExperimentalSlow 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
Receives: Drug: Foxy-5

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6 month

Secondary outcomes (12)

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

    Determination of the biological response dose (BRD) based on the alterations in the exploratory biomarkers during treatment with Foxy-5

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

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

    Determination of the biological response dose (BRD) based on the alterations in the exploratory biomarkers during treatment with Foxy-5

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

  3. Numbers of circulating tumour cells (CTCs) in blood

    Determination of the biological response dose (BRD) based on the alterations in the exploratory biomarkers during treatment with Foxy-5

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

  4. Maximum tolerated dose (MTD)

    Determined as the dose preceding the dose at which two or more patients have experienced DLTs. Assessment of adverse events and laboratory abnormalities

    Measured: 6 month

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

    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

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

  6. Bioavailability (F) of Foxy-5

    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

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

  7. Half life (T½) of Foxy-5

    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

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

  8. Absorption rate Constant (tmax) of Foxy-5

    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

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

  9. Volume of distribution (V) of Foxy-5

    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

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

  10. Clearance (C) of Foxy-5

    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

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

  11. Extraction Ratio (E) of Foxy-5

    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

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

  12. Hepatic and Renal Clearance of Foxy-5

    The concentration of Foxy-5 in human biological samples will be measured with liquid chromatography with tandem mass spectrometry detection (LC-MS/MS)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jan 2016 (estimated)
  2. Study startApr 2016
  3. Primary completionOct 2017
  4. Study completionOct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02655952
Sponsor's protocol ID
SMR-3164
Status last verified
Feb 2018
First submitted
6 Jan 2016
Last updated
28 Dec 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Foxy-5 in people with Metastatic Breast Cancer and Metastatic Colon Cancer, run by WntResearch AB at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Denmark, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Presence of Dose Limiting Toxicities (DLTs). (time frame: 6 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02655952.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2018.

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