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

NCT ID: NCT01410968

Last Updated: 2016-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2015-05-31

Brief 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.

Detailed 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)

Conditions

Metastatic Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vaccination

vaccination with investigational Poly-ICLC \& peptide-pulsed dendritic cells

Group Type: EXPERIMENTAL

vacc. w/ Poly-ICLC & peptide-pulsed dendritic cells

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oncovir, Inc.

INDUSTRY

Sponsor Role: collaborator

Carolyn Britten

OTHER

Sponsor Role: lead

Responsible Party

Carolyn Britten

Chief, Hematology/Oncology Division

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

References

Mehrotra S, Britten CD, Chin S, Garrett-Mayer E, Cloud CA, Li M, Scurti G, Salem ML, Nelson MH, Thomas MB, Paulos CM, Salazar AM, Nishimura MI, Rubinstein MP, Li Z, Cole DJ. Vaccination with poly(IC:LC) and peptide-pulsed autologous dendritic cells in patients with pancreatic cancer. J Hematol Oncol. 2017 Apr 7;10(1):82. doi: 10.1186/s13045-017-0459-2.

Reference Type: DERIVED

PMID: 28388966 (View on PubMed)

Other Identifiers

101498

Identifier Type: -

Identifier Source: org_study_id