Safety and Efficacy Study of Epitope Peptide To Treat HLA-A*24 or A*02-positive Advanced Solid Tumors

Phase I/II Study Using Epitope Peptide Restricted to HLA-A*24 or HLA-A*02 in Patients With Advanced Solid Tumors That Are Refractory to Standard Therapy

In this study, the investigators examine using a combination of two types of HLA-A*2402 (or HLA-A*0201)-restricted epitope peptides, which were derived from VEGF-R1 and VEGF-R2 the safety, immunogenicity, and antitumor effect of vaccine treatment for advanced solid tumor patients who are refractory to standard therapy.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Biological: HLA-A*2402 or A*0201 restricted peptides

Detailed Description

The purpose of this study is to evaluate the safety, tolerability, immune response and clinical efficacies of HLA-A*2402 or HLA-A*0201 restricted epitope peptides (VEGF-R1 and VEGF-R2) emulsified with Montanide ISA 51 for advanced solid tumors.

In this phase I/II trial, the investigators examine using a combination of the two peptides the safety, immunogenicity, and antitumor effect of vaccine treatment for HLA-A*2402 or HLA-A*0201-positive advanced solid tumor patients who are refractory to standard therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 26
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Shiga
    • Ohtsu, Shiga, Japan, 520-2192
      • Shiga University of Medical Science Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Advanced solid tumors that are refractory to standard therapies or that cannot be treated with those due to medical reason.
2. ECOG performance status 0-1
3. Age between 20 to 85
4. Clinical efficacy can be evaluated by some methods
5. No prior chemotherapy, radiation therapy, hyperthermia or immunotherapy within two weeks
6. Life expectancy > 3 months
7. Laboratory values as follows 1500/mm3 < WBC < 10000/mm3 Platelet count > 75000/mm3 15% < Lymphcyte fraction Asparate transaminase < 3 X cutoff value Alanine transaminase < 3 X cutoff value Total bilirubin < 3 X cutoff value Serum creatinine < 2X cutoff value
8. HLA-A*2402 or HLA-A*0201
9. Able and willing to give valid written informed consent

Exclusion Criteria:

1. Active and uncontrolled cardiac disease (i.e. coronary syndromes, arrhythmia)
2. Myocardial infarction within six months before entry
3. Breastfeeding and Pregnancy (woman of child bearing potential)
4. Active and uncontrolled infectious disease
5. Concurrent treatment with steroids or immunosuppressing agent
6. Other malignancy requiring treatment
7. Non-cured traumatic wound
8. Decision of unsuitableness by principal investigator or physician-in-charge

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLA-A*2402 restricted peptides; HLA-A*2402 restricted peptides with adjuvant	Biological: HLA-A*2402 or A*0201 restricted peptides; Open Label, Non-Randomized, Safety/Efficacy study: HLA-A*2402-positive patients will be vaccinated subcutaneously once a week with HLA-A*2402 restricted peptides for VEGF-R1 and VEGF-R2 with adjuvant.; HLA-A*0201-positive patients will be vaccinated subcutaneously once a week with HLA-A*0201 restricted peptides for VEGF-R1 and VEGF-R2 with adjuvant.
Experimental: HLA-A*0201 restricted peptides; HLA-A*0201 restricted peptides with adjuvant	Biological: HLA-A*2402 or A*0201 restricted peptides; Open Label, Non-Randomized, Safety/Efficacy study: HLA-A*2402-positive patients will be vaccinated subcutaneously once a week with HLA-A*2402 restricted peptides for VEGF-R1 and VEGF-R2 with adjuvant.; HLA-A*0201-positive patients will be vaccinated subcutaneously once a week with HLA-A*0201 restricted peptides for VEGF-R1 and VEGF-R2 with adjuvant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of safety: the number of adverse events of vaccination therapy.	2 months
Evaluation of clinical efficacy: Overall survival.	2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Various immunological responses including peptides specific CTL, antigen cascade, regulatory T cells, cancer antigens and HLA levels.	2 months
Evaluation of clinical efficacy: Progression free survival.	2 months
Evaluation of clinical efficacy: Tumor markers.	2 months
Evaluation of clinical efficacy: Objective response rate.	2 months

Collaborators and Investigators

• Sponsor: Shiga University
• Collaborators: Tokyo University
• Investigators: Principal Investigator: Yataro Daigo, MD, PhD, Shiga University

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: September 20, 2013
• First Submitted That Met QC Criteria: September 20, 2013
• First Posted (Estimate): September 24, 2013

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 15, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: SUMS-22-15; 22-15 (Other Identifier: Shiga University)