Phase I Dose Escalation Study of AB-16B5 in Subjects With an Advanced Solid Malignancy

Solid Tumor Clinical Trial

Official title:

A Phase I Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AB-16B5 in Subjects With an Advanced Solid Malignancy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02412462
• Other study ID #: AB-16B5-101
• Status: Completed
• Phase: Phase 1
• First received: March 30, 2015
• Last updated: June 27, 2017
• Start date: April 2015
• Est. completion date: January 2017

Study information

• Verified date: July 2016
• Source: Alethia Biotherapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1 clinical study to investigate the safety, pharmacokinetics and pharmacodynamics of AB-16B5 in patients with an advanced solid malignancy. AB-16B5 is a humanized monoclonal antibody that inhibits the activity of the secreted form of clusterin (sCLU), a potent inducer of the epithelial-to-mesenchymal transition (EMT). Eligible subjects will have a disease that has been refractory to prior therapy and is unlikely to benefit from known therapies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects with a histologically or cytologically confirmed advanced solid malignancy that has been refractory to prior therapy and is unlikely to benefit from known therapies.

• Subjects may have measurable or non-measurable but evaluable disease.

• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of = 2 and an estimated life expectancy of at least 12 weeks.

• Subjects must be = 18 years old.

• Male, or female subjects who are post-menopausal (amenorrheic for at least 12 months), or surgically or biologically sterile. Females of childbearing potential with a negative serum pregnancy test prior to entering the study and using adequate forms of contraception for the duration of the study, including 30 days after the last treatment. Males should avoid fathering children during the course of the study, and adequate methods of contraception should be used by both male and female subjects. Subjects and their partners with reproductive potential must use an effective contraceptive method while the subject is on the study treatment and for 30 days after the last treatment.

• Subjects must have adequate organ and immune function as indicated by the following laboratory values:

• ANC = 1.5 X 109/L

• Platelets > 100 X 109/L

• Hemoglobin = 90 g/L

• Serum creatinine = 132 µmol/L

• Total Bilirubin = 1.5 X ULN

• AST (SGOT) and ALT (SGPT) = 3 X ULN* or;

• 5 X ULN* (if hepatic metastases present)

• ULN: Institution's upper limit of normal

• Subjects enrolled in the standard dose escalation portion of the study must have a tumor lesion amenable for biopsy with no contraindications for biopsy.

• Subjects must understand and be able and willing and likely to fully comply with the study procedures, including scheduled follow-up, and restrictions.

• Subjects must have given written personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines, before completing any study related procedures.

Exclusion Criteria:

• Subjects with medical, social, or psychosocial factors that, in the opinion of the Investigator, could impact safety or compliance with study procedures.

• Prior cancer therapy including surgery, radiotherapy, chemotherapy, hormonal and biological therapies within 3 weeks prior to study treatment.

• Uncontrolled brain metastases.

• Uncontrolled infection.

• Clinically significant ECG abnormalities.

• Known hypersensitivity of Grade > 2 to previous monoclonal antibody therapy.

• History of alcohol or other substance abuse within the last year.

• Use of another investigational agent in a clinical trial within the last 4 weeks prior to study treatment.

• Female subjects who are pregnant or lactating, including females with a positive pregnancy test at screening must be excluded.

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Solid Tumor

Intervention

Drug:
• AB-16B5

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Alethia Biotherapeutics

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with an adverse event as a measure of safety and tolerability		Up to treatment discontinuation + 30 days with an estimated treatment duration of 6 to 24 weeks
Secondary	Determination of plasma concentrations of AB-16B5		Several time-points during Cycle 1 and Cycle 2 for a total of 6 weeks
Secondary	Objective tumor responses in subjects with measurable disease according to RECIST		Up to treatment discontinuation + 30 days with an estimated treatment duration of 6 to 24 weeks
Secondary	Monitoring of epithelial-to-mesenchymal (EMT) and stem cells biomarkers in peripheral blood circulating tumor cells and paired tumor biopsies		Up to treatment discontinuation + 30 days with an estimated treatment duration of 6 to 24 weeks