Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Closed	18 and over	NCI	JHOC-J0501 J0501, JHOC-05021103, JHOC-05042610, BMS-CA225247, NCT00305760

Objectives

Primary

1. Determine the safety of sargramostim plasmid DNA pancreatic tumor cell vaccine, cyclophosphamide, and cetuximab in patients with metastatic or locally advanced adenocarcinoma of the pancreas.

Secondary

1. Determine the overall, progression-free, and event-free survival of patients treated with this regimen.
2. 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.
3. 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.
4. 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.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

• 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

Patient Characteristics:

• ECOG performance status 0-1
• WBC ≥ 3,500/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 9 g/dL
• Platelet count ≥ 90,000/mm³
• 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

Expected Enrollment

A total of 60 patients will be accrued for this study.

Outcomes

Event-free survival

Outline

This is an open-label study.

Patients receive cyclophosphamide IV on day 0, sargramostim plasmid DNA pancreatic tumor cell 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.

Trial Contact Information

Trial Lead Organizations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Daniel Laheru, MD, Principal investigator		Ph: 410-955-8974

Registry Information
Official Title		A Safety and Efficacy Trial of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected with the GM-CSF Gene in Combination with Erbitux (Cetuximab) for the Treatment of Advanced Pancreatic Adenocarcinoma
Trial Start Date		2005-12-15
Trial Completion Date		2008-12-01 (estimated)
Registered in ClinicalTrials.gov		NCT00305760
Date Submitted to PDQ		2005-12-12
Information Last Verified		2009-02-08
NCI Grant/Contract Number		CA06973

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