Pancreas Neoplasms, Pancreatic Cancer
Conditions
Keywords
cancer, pancreas, advanced, peptide, vaccination, VEGFR1, HLA, gemcitabine, IFA, Cancer of Pancreas, Neoplasms, Pancreas, Pancreas Cancer
Brief summary
Pancreatic cancer is the fourth leading cause of cancer death in the United States, and no combination therapy is far superior to gemcitabine alone. Vascular endothelial growth factor receptor type 1 (VEGFR1) is expressed on the tumor vessels and a candidate of tumor vessel-specific peptide vaccination strategy to induce T cell immune response. We conducted the study to confirm the safety and efficacy of combined modality intervention using conventional dose of gemcitabine with peptide vaccination targeting tumor-vessel specific VEGFR1 in case of advanced/inoperable or therapy-resistant pancreatic cancer patients. Gemcitabine 1,000 mg/m\^2 (body surface area) will be administered on day 1, day 8, day 15, day 29, day 36, and day 43, respectively. VEGFR1-derived HLA-A\*02:01-restricted peptide (VEGFR1-A02-770; TLFWLLLTL) emulsified with Montanide ISA51 will be subcutaneously injected twice weekly for 8 weeks (total 16 doses).
Detailed description
HLA-A\*02:01-restricted VEGFR1-specific cytotoxic T lymphocyte (CTL) responses were obtained from HLA-A2/Kd transgenic murine model. HLA-A\*02:01-restricted VEGFR1-specific CTL clones were also obtained from peripheral blood mononuclear cells of healthy volunteer donors. These CTL clones showed potent anti-tumor CTL responses in HLA class Ⅰ-restricted manner in vitro. Vaccination of HLA-A\*02:01-restricted VEGFR1-specific peptide to A2/Kd transgenic mice markedly suppress the tumor-induced angiogenesis and tumor growth in vivo.
Interventions
BIOLOGICALHLA-A*02:01-restricted VEGFR1-derived peptide vaccination
VEGFR1-derived HLA-A\*02:01-restricted peptide (VEGFR1-A2-770; TLFWLLLTL)was vaccinated twice weekly for 8 weeks (total 16 doses) combined with conventional dose (1,000 mg/m\^2 body surface area) of gemcitabine 6 doses for advanced stage pancreatic cancer to confirm the feasibility and efficacy of this type of peptide.
Sponsors
Human Genome Center, Institute of Medical Science, University of Tokyo
Tokyo University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Heterozygote or homozygote of HLA-A\*02:01 allele * Inoperable or recurrent pancreatic cancer with or without any prior therapy * Difficult to continue the prior therapy due to treatment-related toxicities * ECOG performance status 0-2 * Evaluable primary or metastatic lesion with RECIST v.1.0 criteria * Clearance period from prior therapy more than 4 weeks * Life expectancy more than 3 months * Laboratory values as follows 2,000/μL\< WBC \<15,000/μL Platelet count \>100,000/μL AST \<150 IU/L ALT \<150 IU/L Total bilirubin \<3.0 mg/dl Serum creatinine \<3.0 mg/dl
Exclusion criteria
* Pregnancy (refusal or inability to use effective contraceptives) * Breastfeeding * Active or uncontrolled infection * Systemic use of corticosteroids or immunosuppressants * Uncontrollable brain metastasis and/or meningeal infiltration * Unhealed external wound * Possibilities of complicated paralytic ileus or interstitial pneumonitis * Decision of not eligible determined by principal investigator or attending doctor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Without Grade 4 Hematological or Grade 3 to 4 Non-hematological Adverse Events | 2 months | Number of participants without grade 4 hematological or grade 3 other adverse events were caslculated based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v.3) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Tumor Regression | 2 months | Sum of diameters of primary pancreatic tumor or metastatic tumors (target lesions) before and after vaccination were measured by computed tomography. Sum of tumors' size diameters decrease more than 30% after vaccination was diagnosed as response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines. |
Countries
Japan
Participant flow
Recruitment details
Neighboring research hospitals around Tokyo, Japan sent three candidates to our hospital during May, 2008 to March, 2009.
Pre-assignment details
Wash out time was four weeks from preceding therapy, and three candidates were evaluated for eligibility. Two cases were compatible to our eligibility, but another candidate was excluded from this study entry because he was not expected to survive more than three months.
Participants by arm
| Arm | Count |
|---|---|
| Peptide 1 mg Twice Weekly for 8 Weeks With Gemcitabine HLA-A\*0201-restricted VEGFR1-specific peptide, VEGFR1-A02-770(TLFWLLLTL) 1 mg, subcutaneous injection, twice every weeks for eight weeks (total 16 doses) combined with incomplete Freund adjuvant (IFA) and gemcitabine 1,000 mg/m\^2 of body surface area | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Peptide 1 mg Twice Weekly for 8 Weeks With Gemcitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age Continuous | 55 years STANDARD_DEVIATION 7.07 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 1 / 2 |
Outcome results
Primary
Number of Participants Without Grade 4 Hematological or Grade 3 to 4 Non-hematological Adverse Events
Number of participants without grade 4 hematological or grade 3 other adverse events were caslculated based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v.3)
Time frame: 2 months
Population: Intention to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peptide 1 mg Twice Weekly for 8 Weeks With Gemcitabine | Number of Participants Without Grade 4 Hematological or Grade 3 to 4 Non-hematological Adverse Events | 1 participants |
Secondary
Number of Participants With Tumor Regression
Sum of diameters of primary pancreatic tumor or metastatic tumors (target lesions) before and after vaccination were measured by computed tomography. Sum of tumors' size diameters decrease more than 30% after vaccination was diagnosed as response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines.
Time frame: 2 months
Population: intension to treat (ITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peptide 1 mg Twice Weekly for 8 Weeks With Gemcitabine | Number of Participants With Tumor Regression | 0 participants |