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

WntResearch

Status and phase: Completed; Phase 1

Conditions: Metastatic Prostate Cancer; Metastatic Breast Cancer; Metastatic Colon Cancer

Treatments: Drug: Foxy-5

Study type: Interventional

Funder types: Industry

Identifiers

NCT02655952

SMR-3164

Details and patient eligibility

About

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).

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 1 patient group

Foxy-5

Experimental group

Description:

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

Treatment:

Drug: Foxy-5