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

NCT ID: NCT02655952

Last Updated: 2018-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2017-10-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Foxy-5

Intervention Type: DRUG

Interventions

Foxy-5

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

WntResearch AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tine Mølvadgaard, M.Sc.Pharm

Role: STUDY_DIRECTOR

Smerud Medical Research Denmark

Locations

Clinical Research Department, Oncology, Rigshospitalet

Copenhagen, , Denmark

Onkologisk Afdeling R, Herlev Hospital

Herlev, , Denmark

Odense University Hospital

Odense, , Denmark

NCCC, Freeman Hospital

Newcastle, Newcastle Upon Tyne, United Kingdom

Countries

Denmark; United Kingdom

Other Identifiers

SMR-3164

Identifier Type: -

Identifier Source: org_study_id