Phase I Study to Evaluate Safety, Tolerability, Anti-Tumour Activity and PK Profiles of Foxy-5 in 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 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.


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
* 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
* 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