Clinical trial NCT01227772: Study of OTSGC-A24 Vaccine in Advanced Gastric Cancer
Official title: A Phase I/IIa Study of OTSGC-A24 Vaccine in Advanced Gastric Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Gastric Cancer
Keywords: gastric cancer vaccine
OTSGC-A24
A Phase I/IIa study
HLA-A24-positive
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
Collaborators: name: Wakayama Medical University
name: Severance Hospital
First posted: 2010-10-25
Enrollment: 23
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Active vaccination with tumor specific antigens and VEGFR1 HLA-A24 epitopes can improve survival of patients with advanced Gastric Cancer.

Detailed description: Although palliative chemotherapy improved the outcome of patients with advanced Gastric Cancer, the prognosis for this group of patients remains poor. Tumor specific antigens and angiogenesis pathway are potential targets for immunotherapy. A cocktail of peptide vaccines is selected to overcome gastric cancer's heterogeneous and enhance the anti-tumor effect. Five HLA-A\*2402-binding peptide vaccines derived from tumor specific antigens and VEGFR1 are chosen based on the frequencies of their expressions in gastric cancer and the ability to induce specific cytotoxic T-lymphocytes. In preclinical model, both down regulation these targets with siRNA and active vaccination resulted in tumor regression. The purpose of the study is to evaluate the safety and optimal dosing schedule of a cancer vaccine cocktail, OTSGC-A24 targeting novel specific tumor antigens FOXM1, DEPDC1, KIF20A, URLC10 and VEGFR1 in advanced gastric cancer patients with HLA-2402 haplotype.

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed inoperable or metastatic adenocarcinoma of the stomach or lower third of the oesophagus refractory or intolerable to standard therapy.
* Patients must have measurable or evaluable disease.
* Age \>= 201years
* ECOG performance status of 0 to 2
* Life expectancy at least 3 months
* Patients must have normal organ and marrow function as defined below:
* absolute neutrophil count \>=1,500/mcL
* platelets \>=100,000/mcL
* total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SGPT) \<=2.5 X institutional upper limit of
* Normal creatinine within normal institutional limits
* Patients must be HLA-A\*2402
* Patients must have recover from all reversible treatment toxicity from prior chemotherapy, radiotherapy or surgery.
* The effects of OTSGC-A24 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Patients receiving any other investigational agents.
* History of significant gastrointestinal bleeding that required intervention within the prior 1 month is ineligible; inherited bleeding diathesis or coagulopathy.
* Serious non healing wound and peptic ulcer disease
* Previous history of intestinal perforation
* Invasive procedures defined as follows (Insertion of a vascular access device is not considered major/minor surgery):
* Major surgical procedure, open biopsy or significant traumatic injury =28 days prior to -registration
* Anticipation of need for major surgical procedures during the course of the study
* Core biopsy \<=7 days
* Minor surgery \<=2 weeks
* Symptomatic CNS metastasis
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension (systolic \>150 mmHg and/or diastolic \>100 mmHg), symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction/cerebrovascular event (\<=6 months prior to study entry), cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, long term systemic immunosuppressant or corticosteroid.
* Women who are breast-feeding or pregnant are excluded from this study

Primary outcomes:
measure: safety of OTSGC-24
timeFrame: within 4 weeks of treatment
measure: Optimal dosing schedule
timeFrame: 1 year
Secondary outcomes:
measure: Induction of specific cytotoxic T-lymphocyte (CTL) response
timeFrame: after 4 weeks and 12 weeks of vaccination
Other outcomes:
Locations:
city: Wakayama
country: Japan
facility: Wakayama Medical University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University Hospital, Singapore
name: Wei Peng Yong, MRCP, MB ChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ajani JA. Evolving chemotherapy for advanced gastric cancer. Oncologist. 2005;10 Suppl 3:49-58. doi: 10.1634/theoncologist.10-90003-49.
citation: Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006 Jun 20;24(18):2903-9. doi: 10.1200/JCO.2005.05.0245.
citation: Sundar R, Rha SY, Yamaue H, Katsuda M, Kono K, Kim HS, Kim C, Mimura K, Kua LF, Yong WP. A phase I/Ib study of OTSGC-A24 combined peptide vaccine in advanced gastric cancer. BMC Cancer. 2018 Mar 27;18(1):332. doi: 10.1186/s12885-018-4234-8.