Combination Chemotherapy With or Without Oregovomab and Stereotactic Radiotherapy Together With Nelfinavir Mesylate in Treating Patients With Localized or Locally Advanced Pancreatic Cancer

This study is currently recruiting participants.
Verified December 2013 by University of Nebraska
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Chi Lin, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01959672
First received: October 8, 2013
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

This study is being done to test the safety and effects (good and bad) of pre-surgery chemotherapy followed by nelfinavir (nelfinavir mesylate) (a drug approved by Food and Drug Administration [FDA] for human immunodeficiency virus [HIV] infection) and with or without immunotherapy to cancer antigen-125 (CA125) using oregovomab (an experimental murine monoclonal antibody agent for the treatment of cancers that express the tumor associated antigen CA125, are CA125 positive) administered with a special form of radiation "hypofractionated stereotactic radiotherapy (SRT)". Nelfinavir is being used to make tumor cells more sensitive to the radiation. A purpose of this research study is to determine if immunotherapy with oregovomab can create an immune response and enable the body to fight pancreatic cancer in patients that have a positive CA125 laboratory value


Condition Intervention Phase
Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IA Pancreatic Cancer
Stage IB Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer
Biological: oregovomab
Drug: gemcitabine hydrochloride
Drug: leucovorin calcium
Drug: fluorouracil
Drug: nelfinavir mesylate
Radiation: stereotactic body radiation therapy
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Neoadjuvant Chemotherapy With and Without Immunotherapy to CA125 (Oregovomab) Followed by Hypofractionated Stereotactic Radiotherapy and Concurrent HIV Protease Inhibitor Nelfinavir in Patients With Locally Advanced Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Disease progression, defined as at least a 25% increase in the longest diameter of a lesion, taking as reference the longest diameter recorded since the treatment started [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
    The number and proportion of patients experiencing progressive disease (PD) will be reported. An exact one-sided 90% confidence interval will be constructed around the progressive disease rate.


Secondary Outcome Measures:
  • Toxicities due to oregovomab, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Failure-free survival [ Time Frame: The time from the date of administration study drug to the date of first appearance of tumor lesions by imaging, or death, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: The time from the date of first of study drug to the date of death, assessed up to 5 years ] [ Designated as safety issue: No ]
  • Surgical complete resection (negative margin) rate [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
  • Tumor response rate on pathology specimen, assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Tumor response rate on computed tomography (CT)/magnetic resonance imaging (MRI), assessed according to RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 66
Study Start Date: September 2013
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, immunotherapy, radiation, surgery)

CHEMOTHERAPY: Patients receive gemcitabine hydrochloride IV, leucovorin calcium IV over 30 minutes, and fluorouracil IV over 24 hours on days 1 and 8. Treatment repeats every 21 days for 3 courses (weeks 1-9) and then post-SRT for a fourth course (weeks 14-16).

IMMUNOTHERAPY: Patients with CA125 >= 10 receive oregovomab IV over 15-30 minutes on day 15 of courses 1-4.

NELFINAVIR MESYLATE: Patients receive nelfinavir mesylate PO BID for 5 weeks starting day 15 of course 3 (weeks 9-13).

STEREOTACTIC RADIOTHERAPY: Patients undergo SRT daily for 5 days (week 11) and then resume nelfinavir mesylate PO BID for 14 days (weeks 12-13).

SURGERY: Patients with resectable disease and without metastases undergo definitive surgery (weeks 17-18), followed by 3 additional courses of chemotherapy with or without immunotherapy. If surgical resection is not possible, patients proceed directly to the additional chemotherapy courses.

Biological: oregovomab
Given IV
Other Names:
  • B43.13
  • MOAB B43.13
  • monoclonal antibody B43.13
  • OvaRex
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: nelfinavir mesylate
Given PO
Other Name: Viracept
Radiation: stereotactic body radiation therapy
Undergo SRT
Other Names:
  • SBRT
  • stereotactic radiation therapy
  • stereotactic radiotherapy
Procedure: therapeutic conventional surgery
Undergo definitive surgery
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of neoadjuvant chemotherapy, (gemcitabine [gemcitabine hydrochloride], leucovorin [leucovorin calcium], 5-FU [fluorouracil]) with or without oregovomab, followed by hypofractionated stereotactic radiotherapy (SRT) concurrently with nelfinavir in patients with locally advanced pancreatic cancer that is CA125 positive (>= 10) or CA125 negative (< 10).

SECONDARY OBJECTIVES:

I. To assess the safety of neoadjuvant chemotherapy, (gemcitabine, leucovorin, 5-FU) with or without oregovomab, followed by SRT concurrently with nelfinavir in patients with locally advanced pancreatic cancer that is CA125 positive (>= 10) or CA125 negative (< 10).

II. To assess the cellular and humoral immune responses to active immunotherapy with oregovomab/ monoclonal antibody in patients with pancreas cancer with CA125 level greater than 10 undergoing chemotherapy and radiation treatments.

TERTIARY OBJECTIVES:

I. To measure nelfinavir pharmacokinetics at steady-state. II. To evaluate the value of 4-dimensional computed tomography (4DCT) and respiratory gating in pancreatic cancer SRT.

OUTLINE:

CHEMOTHERAPY: Patients receive gemcitabine hydrochloride intravenously (IV), leucovorin calcium IV over 30 minutes, and fluorouracil IV over 24 hours on days 1 and 8. Treatment repeats every 21 days for 3 courses (weeks 1-9) and then post-SRT for a fourth course (weeks 14-16).

IMMUNOTHERAPY: Patients with CA125 >= 10 receive oregovomab IV over 15-30 minutes on day 15 of courses 1-4.

NELFINAVIR MESYLATE: Patients receive nelfinavir mesylate orally (PO) twice daily (BID) for 5 weeks starting day 15 of course 3 (weeks 9-13).

STEREOTACTIC RADIOTHERAPY: Patients undergo SRT daily for 5 days (week 11) and then resume nelfinavir mesylate PO BID for 14 days (weeks 12-13).

SURGERY: Patients with resectable disease and without metastases undergo definitive surgery (weeks 17-18), followed by 3 additional courses of chemotherapy with or without immunotherapy. If surgical resection is not possible, patients proceed directly to the additional chemotherapy courses.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for the 2nd year, and then every 6 months thereafter.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Pathologically confirmed adenocarcinoma of the pancreas; patients have localized or locally advanced disease with no evidence of distant metastases; the maximum dimension of the tumor must be =< 8 cm Karnofsky performance status of 60% or better Patients who received chemotherapy > 5 years ago for malignancies other than pancreatic cancer are eligible, provided that chemotherapy was completed > 5 years ago and that there is no evidence of the second malignancy at the time of study entry Patients who received radiation therapy > 5 years ago for malignancies other than pancreatic cancer and whose radiation therapy field is not overlapping with the 20% isodose line of current radiation field are eligible, provided that radiation therapy was completed > 5 years ago and that there is no evidence of the second malignancy at the time of study entry All malignant disease must be able to be encompassed within a single irradiation field All patients must have radiographically assessable disease Patients must have an absolute neutrophil count (ANC) greater than or equal to 1500/uL Platelet count greater than or equal to 100,000/uL Patients must have a serum creatinine less than or equal to 2.0 mg/dL Total bilirubin less than or equal to 2.0 mg/dL in the absence of biliary obstruction; if the patient has biliary obstruction, biliary decompression will be required; either endoscopic placement of biliary stent (7 French or greater) or percutaneous transhepatic drainage are acceptable; once biliary drainage has been established, institution of gemcitabine therapy may proceed when the total bilirubin falls to below 4.0 mg/dL; patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting chemoradiation The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts Patients may have had prior chemotherapy for pancreatic cancer Patients must have CA125 level >= 10 to participate in the immunotherapy aspect of the trial and receive oregovomab; if the patient has CA125 >= 10 who is not eligible to receive oregovomab (e.g. allergic to the drug) but is eligible for the rest of treatment, this patient should be accrued to the part of protocol without oregovomab

Exclusion Criteria:

Patients who cannot undergo staging laparoscopy; for example, this may include patients with a prior history of multiple abdominal operations in which laparoscopy may not be technically feasible or potentially harmful; the patient is eligible if they have a common bile duct stent adjacent to the tumor that may be used as an internal marker, or if the patient has already had a staging laparoscopy without marker implantation and the markers can be implanted (by interventional radiology) prior to the beginning of radiation therapy Patients with a known allergy to murine proteins or have had a documented anaphylactic reaction or allergy to any of chemotherapy agents used in this protocol, oregovomab, or to antiemetics appropriate for administration in conjunction with protocol-directed therapy Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the therapy program outlined in this protocol with reasonable safety Pregnant and nursing women are excluded from this study Patients with prior malignancy will be excluded except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years Patients with active duodenal ulcer or bleeding or history of a gastrointestinal fistula or perforation or other significant bowel problems (severe nausea, vomiting, inflammatory bowel disease and significant bowel resection) Patients with known HIV infection, or hepatic insufficiency Patients who cannot take oral medications Patients may not be receiving or have received any other investigational agents during/or within 1 month prior to treatment with oregovomab or nelfinavir Patients with an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus [SLE], ulcerative colitis, Crohn's disease, multiple sclerosis [MS], ankylosing spondylitis) Patients with a recognized acquired, hereditary, or congenital immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia Patients receiving the following drugs that are contraindicated with NFV (nelfinavir mesylate) (VIRACEPT) will be excluded if they cannot be change or discontinued

  • Antiarrhythmatics: amiodarone, quinidine
  • Antimycobacterial: rifampin
  • Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine
  • Herbal products: St. John's wort (hypericum perforatum)
  • Hydroxymethylglutaryl-coenzyme A reductase inhibitor (HMG CoA): lovastatin, simvastatin
  • Neuroleptic: pimozide
  • Sedative/hypnotics: midazolam, triazolam

Patients receiving the following drugs will be clinically evaluated as to whether dosage/medication can be changed to permit patient on study:

  • Anti-convulsants: carbamazepine, phenobarbital
  • Anti-convulsant: phenytoin
  • Anti-mycobacterial: rifabutin
  • Erectile dysfunction agent: sildenafil
  • HMG-CoA reductase inhibitor: atorvastatin
  • Immunosuppressants: cyclosporine, tacrolimus, sirolimus
  • Narcotic agents: methadone
  • Oral contraceptive: ethinyl estradiol
  • Macrolide antibiotic: azithromycin
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01959672

Locations
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-6805
Contact: Chi Lin    402-552-3844    llarson@unmc.edu   
Principal Investigator: Chi Lin         
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Chi Lin University of Nebraska
  More Information

No publications provided

Responsible Party: Chi Lin, MD, Medical Oncologist, University of Nebraska
ClinicalTrials.gov Identifier: NCT01959672     History of Changes
Other Study ID Numbers: 441-13, NCI-2012-00835, P30CA036727
Study First Received: October 8, 2013
Last Updated: December 12, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pancreatic Neoplasms
Adenocarcinoma
Carcinoma, Acinar Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antibodies, Monoclonal
Fluorouracil
Gemcitabine
Leucovorin
Levoleucovorin
Protease Inhibitors
Nelfinavir
HIV Protease Inhibitors
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents

ClinicalTrials.gov processed this record on April 23, 2014