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

• Status: Completed
• Trial end date: 2015-11-01
• Target enrollment: 0
• Participant gender: All

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 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: WntResearch AB

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