Patient case: 81-year-old male with Prostate cancer. Genetic variant: PTEN Inactivating. Other conditions: Hypertension, Depression.

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

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).


Eligibility: 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

Relevance to patient case: not relevant