Vaccine Therapy, Cyclophosphamide, And Cetuximab In Treating Patients With Metastatic Or Locally Advanced Pancreatic Cancer

Study Overview

Vaccine Therapy, Cyclophosphamide, and Cetuximab in Treating Patients With Metastatic or Locally Advanced Pancreatic Cancer

RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vaccine therapy together with cyclophosphamide and cetuximab may kill more tumor cells. PURPOSE: This phase II trial is studying how well vaccine therapy works when given together with cyclophosphamide and cetuximab in treating patients with metastatic or locally advanced pancreatic cancer.

OBJECTIVES: Primary * Determine the safety of pancreatic tumor vaccine, cyclophosphamide, and cetuximab in patients with metastatic or locally advanced adenocarcinoma of the pancreas. Secondary * Determine the overall, progression-free, and event-free survival of patients treated with this regimen. * Correlate specific in vivo parameters of immune response (e.g., mesothelin, prostate stem cell antigen [PSCA], mutated k-ras-specific T-cell responses) with clinical response in patients treated with this regimen. * Correlate downstream targets of epidermal growth factor receptor (EGFR) signaling (e.g., intratumor expression of Akt, Stat 3 and 5, mesothelin, mutated k-ras, and PSCA) with inhibition by cetuximab in patients treated with this regimen. * Correlate inhibition of EGFR signaling (e.g., Stat 3 and 5) with improved specific mesothelin, PSCA, and mutated k-ras-specific T-cell responses in patients treated with this regimen. OUTLINE: This is an open-label study. Patients receive cyclophosphamide IV on day 0, sargramostim plasmid DNA pancreatic tumor vaccine intradermally on day 1, and cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsies periodically during study for biomarker correlative studies. At the completion of study treatment, patients are followed at 3 weeks and then every 4 weeks for 16 weeks. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Pancreatic Cancer

DRUG: Cetuximab
BIOLOGICAL: Pancreatic tumor vaccine
DRUG: Cyclophosphamide

J0501
P30CA006973 (U.S. NIH Grant/Contract)
BMS-CA225247

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2006-03-21	Results First Submitted 2015-06-18	Last Update Submitted that met QC Criteria 2020-02-10
First Submitted that Met QC Criteria 2006-03-21	Results First Submitted that Met QC Criteria 2015-06-18	Last Update Posted (ACTUAL) 2020-02-19
First Posted (ACTUAL) 2006-03-22	Results First Posted 2015-07-15	Last Verified 2020-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Cyclophosphamide, Pancreatic Tumor Vaccine, Cetuximab	DRUG: Cetuximab Cetuximab will be administered at an initial dose of 400 mg/m2, followed by weekly doses of 250 mg/m2 for a total of 6 cycles that last 3 weeks each. BIOLOGICAL: Pancreatic tumor vaccine Vaccine will be administered one day after cyclophosphamide (day 1) every three weeks for 6 cycles. DRUG: Cyclophosphamide Cyclophosphamide 250 mg/m2 will be administered one day prior to vaccination (day 0) every three weeks for 6 cycles.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Cyclophosphamide, Pancreatic Tumor Vaccine, Cetuximab

DRUG: Cetuximab

Cetuximab will be administered at an initial dose of 400 mg/m2, followed by weekly doses of 250 mg/m2 for a total of 6 cycles that last 3 weeks each.

BIOLOGICAL: Pancreatic tumor vaccine

Vaccine will be administered one day after cyclophosphamide (day 1) every three weeks for 6 cycles.

DRUG: Cyclophosphamide

Cyclophosphamide 250 mg/m2 will be administered one day prior to vaccination (day 0) every three weeks for 6 cycles.

Primary Outcome Measures	Measure Description	Time Frame
Safety of Combining the Pancreatic Tumor Vaccine in Sequence With Cyclophosphamide and Erbitux. Safety is Defined as the Number of Treatment-related Grade 3 or 4 Adverse Events Observed in Greater Than 5% of the Patient Population		7 months

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically confirmed ductal adenocarcinoma of the pancreas

Mixed adenocarcinoma tumors eligible provided the predominant invasive component of the tumor is adenocarcinoma
The following histologic diagnoses are not eligible:

Adenosquamous
Squamous cell
Colloid
Islet cell
Serous or mucinous cystadenoma or cystadenocarcinoma
Carcinoid
Small or large cell carcinoma
Intraductal oncocytic papillary neoplasms
Osteoclast-like giant cell tumors
Acinar cell carcinoma
Pancreatoblastoma
Solid pseudopapillary tumors
Undifferentiated small cell carcinoma
Nonepithelial tumors (sarcoma, gastrointestinal stromal tumor, lymphoma)
Adenocarcinomas of the ampulla, distal bile duct, or duodenum
Metastatic or locally advanced disease that is refractory to standard therapy OR for which patient refused standard therapy
Measurable disease defined as ≥ 1 lesion unidimensionally measured as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

No nonmeasurable disease only including, but not limited to, the following:

Bone lesions
Leptomeningeal disease
Ascites
Pleural or pericardial effusion
Inflammatory breast disease
Lymphangitis cutis/pulmonis
Abdominal masses that are not confirmed and followed by imaging techniques
Cystic lesions
No known active or untreated brain metastases

ECOG performance status 0-1
WBC ≥ 3,500/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Hemoglobin ≥ 9 g/dL
Platelet count ≥ 90,000/mm^3
Creatinine ≤ 2.0 mg/dL
Bilirubin ≤ 2 mg/dL
ALT and AST ≤ 5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 5 times ULN
No active infection
No uncontrolled medical condition that would potentially increase the risk of toxicities or complications of study therapy
No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
No active peptic ulcer disease
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment
No other malignancy within the past 5 years except for nonmelanomatous skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
HIV negative
No active autoimmune disease or prior autoimmune disease requiring medical treatment with systemic immunosuppressants including any of the following:

Inflammatory bowel disease
Systemic vasculitis
Scleroderma
Psoriasis
Multiple sclerosis
Hemolytic anemia or immune thrombocytopenia
Rheumatoid arthritis
Systemic lupus erythematosus
Sjögren's syndrome
Sarcoidosis
Asthma or chronic obstructive pulmonary disease that does not require systemic corticosteroids or routine use of inhaled steroids allowed
No known or suspected hypersensitivity to sargramostim (GM-CSF), cyclophosphamide, pentastarch, corn, or DMSO
No prior severe infusion reaction (> grade 3) to a monoclonal antibody

See Disease Characteristics
More than 1 month since prior adjuvant chemotherapy
More than 4 weeks since prior surgery except for minor procedures (e.g., dental work, skin biopsy) and biliary stent placement
No prior surgical procedures affecting absorption
More than 4 weeks since prior radiotherapy
More than 1 month since prior participation in an investigational new drug study
No unresolved chronic toxicity (except alopecia) from prior anticancer therapy
More than 28 days since prior systemic steroids
No concurrent systemic steroids or immunosuppressive drugs

Topical, inhaled, and intra-articular steroids allowed
No other concurrent anticancer vaccine therapy
No other concurrent chemotherapy, immunotherapy, radiotherapy, gene therapy, biologic therapy, or investigational therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Daniel A. Laheru, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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