A Feasibility and Safety Study of Vaccination With Poly-ICLC and Peptide-pulsed Dendritic Cells in Patients With Metastatic, Locally Advanced, Unresectable, or Recurrent Pancreatic Adenocarcinoma

Metastatic Pancreatic Cancer Clinical Trial

Official title:

A Feasibility and Safety Study of Vaccination With Poly-ICLC and Peptide-pulsed Dendritic Cells in Patients With Metastatic, Locally Advanced, Unresectable, or Recurrent Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01410968
• Other study ID #: 101498
• Status: Completed
• Phase: Phase 1
• First received: August 4, 2011
• Last updated: December 8, 2016
• Start date: August 2011
• Est. completion date: May 2015

Study information

• Verified date: December 2016
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to provide a safety and feasibility basis for future studies addressing the hypothesis that subcutaneous vaccination with dendritic cells loaded with multiple antigenic epitopes expressed by pancreatic tumor in combination with systemic administration of Poly-ICLC (Hiltonol) will induce anti-tumor immunity.

Description:

Primary Objectives

1. Assess the safety of this treatment by evaluating the qualitative and quantitative toxicities in this group of patients.

2. Determine the feasibility of generating dendritic cells and administering these cells as a vaccine to patients.

Secondary Objectives

1. Assess anti-tumor activity after vaccination, measured by change in tumor burden and overall survival.

2. Assess immunological responses after vaccination (antigen-specific T cell cytokine production, antigen-specific T cell frequencies by tetramer analysis, and DTH reactions)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 2015
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Eligibility Criteria:

• Patients must have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma that is metastatic, locally advanced, unresectable, or recurrent. Patients with endocrine or neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer are not eligible. If the histologic diagnosis is based on a metastatic site, the histology must be compatible with pancreatic cancer.

• Patient must not have clinically significant ascites.

• Patients must be HLA-A2 positivity by serological testing.

• Prior surgery is allowed provided at least 14 days has elapsed between surgery and registration. Prior radiation/chemo is allowed provided that at least 28 days have elapsed since the last treatment.

• One or more tumors measurable on CT scan per RECIST 1.1. (Eisenhauer)

• Eastern Cooperative Oncology Group (ECOG) performance status < 2.

• Age > 18 years.

• Patient must have an expected life expectancy greater than 3 months.

• Signed, written IRB-approved informed consent.

• A negative pregnancy test (if female).

• Acceptable organ function:

• Bilirubin < 3 times upper limit of normal (CTCAE Grade 2 baseline)

• AST (SGOT), ALT (SGPT) < 3 x ULN (CTCAE Grade 1 baseline)

• Serum creatinine < 1.5 XULN (CTCAE Grade 1 baseline)

• Acceptable hematologic status:

• Absolute neutrophil count > 1000 cells/mm3,

• Platelet count > 75,000 (plt/mm3), (CTCAE Grade 1 baseline)

• Hemoglobin > 9 g/dL.

• Urinalysis: No clinically significant abnormalities.

• PT and PTT < 1.5 X ULN after correction of nutritional deficiencies that may contribute to prolonged PT/PTT.

• No evidence of clinically significant, uncontrolled cardiovascular, endocrine, or infectious disease.

Exclusion Criteria

• Patients must not have any serious uncontrolled acute or chronic medical condition that would interfere with this treatment. An example would be an active acute or chronic infection requiring antibiotics

• Patients must not have significant ongoing cardiac problems, myocardial infarction within the last six months, uncontrolled hypertension, unstable angina, uncontrolled arrhythmia or congestive heart failure.

• Patients with known brain metastases are not eligible. However, brain-imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms. If brain-imaging studies are performed, they must be negative for disease.

• Patients must have no plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol treatment.

• Due to the undetermined effect of this treatment regimen in patients with HIV-1 infection and the potential for serious interaction with anti-HIV medications, patients known to be infected with HIV are not eligible for this study.

• Due to the possibility of harm to a fetus or nursing infant from this treatment regimen, patients must not be pregnant or nursing. Women and men of reproductive potential must have agreed to use an effective contraceptive method.

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• vacc. w/ Poly-ICLC & peptide-pulsed dendritic cells
Intradermal injection of 1x107 peptide-pulsed dendritic cells followed by intramuscular injection of 30 micrograms per kilogram Poly-ICLC on days 0, 14, 28 and 42. Additional dose of 30 micrograms per kilogram Poly-ICLC on days 3, 17, 31 and 45. Treatment given via one 56-day cycle. Leukapheresis performed at baseline for dendritic cell generation.

Locations

Country	Name	City	State
United States	Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Carolyn Britten	Oncovir, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility	Any protocol deviations will be described and the protocol schedule will be re-assessed to improve feasibility of implementation if necessary. The proportion of patients successfully completing the protocol (i.e., without deviations) will be reported with a one-sided 90% confidence interval. If the observed feasibility rate is >0.80, the lower limit will be no lower than 0.60.	2 years	Yes
Primary	Safety	All toxicities will be reported by type and grade and tabulated. To provide a safety characterization of the treatment regimen, it is important that common toxicities be observed in this phase of study for planning the next phase of research.	2 Years	Yes
Secondary	Efficacy	Graphical displays of tumor size (as a percentage of baseline) over time. A subject's best response (i.e., complete response, partial response, stable disease or progressive disease) will be reported. Time to disease progression from baseline for each patient will be reported. Time to death will be reported in the same manner. These results will be summarized using proportions with confidence intervals and Kaplan-Meier curves, although the confidence limits are expected to be wide based on the small sample size.	2 years	Yes
Secondary	Immunological Responses	Antigen-specific T cell frequencies, antigen-specific T cell cytokine production and DTH reactions will be assessed.; For T cell-based functional analysis, each measurement will be performed with the three peptides telomerase, CEA, and survivin. Transformation of the continuous outcomes will be logged. Post measurements will be normalized by the baseline value (i.e. we will subtract the baseline value from each of the post vaccination measurements after the log transformations). Each of these measures will be displayed graphically over time for each patient to observe modulations in these measures. If appropriate based on the distribution of values over time, linear longitudinal regression will be used to model the change in these outcomes over time. Appropriateness will be based on the consistency of trends across patients.	2 years	Yes