Combination Chemotherapy With or Without Oregovomab Followed by Stereotactic Body Radiation Therapy and Nelfinavir Mesylate in Treating Patients With Locally Advanced Pancreatic Cancer

Status:Active, not recruiting
Conditions:Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer
Therapuetic Areas:Oncology
Age Range:19 - Any
Start Date:September 2013
End Date:December 2019

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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

This phase II trial studies how well combination chemotherapy with or without oregovomab
followed by stereotactic body radiation therapy (SBRT) and nelfinavir mesylate works in
treating patients with pancreatic cancer that has spread to nearby organs or tissues. Drugs
used in chemotherapy, such as gemcitabine hydrochloride, leucovorin calcium, and
fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal
antibodies, such as oregovomab, can block tumor growth in different ways by targeting certain
cells. Stereotactic body radiation therapy is a specialized radiation therapy that sends
x-rays directly to the tumor using smaller doses over several days and may cause less damage
to normal tissue. Drugs, such as nelfinavir mesylate, may make tumor cells more sensitive to
radiation therapy. Giving combination chemotherapy with or without oregovomab followed by
SBRT and nelfinavir mesylate may kill more tumor cells.


I. To evaluate the efficacy of neoadjuvant chemotherapy, (gemcitabine [gemcitabine
hydrochloride], leucovorin [leucovorin calcium], fluorouracil [5-FU]) with or without
oregovomab, followed by hypofractionated stereotactic radiotherapy (SRT) concurrently with
nelfinavir (nelfinavir mesylate) in patients with locally advanced pancreatic cancer that is
cancer antigen (CA)125 positive (>= 10) or CA125 negative (< 10).


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.


I. To evaluate tumor and organ motion with 4-dimensional (4D) computed tomography (CT) and
respiratory gating system.

II. To evaluate the effect of tumor/organ motion on the dosimetry, local control and

III. To evaluate inter- and intra-fractional target motion with Calypso system.


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 3 weeks for 7 courses.

IMMUNOTHERAPY: Patients with CA125 level >= 10 receive oregovomab IV over 15-30 minutes on
day 15. Treatment repeats every 3 weeks for 3 courses (weeks 1, 4, 7) and post- radiation
therapy for 1 course (week 14). Patients may receive an additional 3 courses concurrently
with chemotherapy upon recovery from surgery based on CA125 level. Patients also receive
nelfinavir mesylate orally (PO) twice daily (BID) for 5 weeks beginning on day 15 of week 9.

STEREOTACTIC RADIATION THERAPY: Beginning in week 11, patients undergo SBRT in 5 fractions
over 5 consecutive days. Upon completion of radiation therapy, patients resume nelfinavir
mesylate for 14 days (week 12-13). Patients without metastasis and with resectable disease
undergo surgery in week 17-18.

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

Inclusion Criteria:

- Pathologically confirmed adenocarcinoma of the pancreas; patients have resectable
borderline resectable disease, or unresectable disease with no evidence of distant
metastases or peritoneal disease; the maximum dimension of the tumor must be =< 10 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

- Absolute neutrophil count (ANC) greater than or equal to 1500/uL

- Platelet count greater than or equal to 100,000/uL

- 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 =<
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

- No prior therapy with the exception of 1 cycle of chemotherapy based on current
diagnosis and clinical condition

- 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

- 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 human immunodeficiency virus (HIV) infection, or hepatic

- 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 immunodeficiency's, hypogammaglobulinemia or

- Patients receiving the following drugs that are contraindicated with nelfinavir (NFV)
(VIRACEPT) will be excluded if they cannot be change or discontinued; drugs that
should not be coadministered with Viracept:

- Antiarrhythmics: amiodarone, quinidine

- Antimycobacterial: rifampin

- Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine

- Herbal products: St. John's wort (hypericum perforatum)

- 3-hydroxy-3-methyl-glutaryl (HMG)-acetyl coenzyme A (CoA) reductase inhibitors:
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; phenytoin plasma/serum concentrations should be
monitored; phenytoin dose may require adjustment to compensate for altered
phenytoin concentration

- Anti-mycobacterial: rifabutin; it is recommended that the dose of rifabutin be
reduced to one-half the usual dose when administered with VIRACEPT; 1250 mg BID
is the preferred dose of VIRACEPT when coadministered with rifabutin

- Erectile dysfunction agent: sildenafil; sildenafil shall not exceed a maximum
single dose of 25 mg in a 48 hour period

- HMG-CoA reductase inhibitor: atorvastatin; use lowest possible dose of
atorvastatin with careful monitoring, or consider other HMG-CoA reductase
inhibitors such as pravastatin or fluvastatin in combination with VIRACEPT

- Immunosuppressants: cyclosporine, tacrolimus, sirolimus

- Narcotic analgesic: methadone; dosage of methadone may need to be increased when
coadministered with VIRACEPT

- Oral contraceptive: ethinyl estradiol; alternative or additional contraceptive
measures should be used when oral contraceptives and VIRACEPT are coadministered

- Macrolide antibiotic: azithromycin; dose adjustment of azithromycin is not
recommended, but close monitoring for known side effects such as liver enzyme
abnormalities and hearing impairment is warranted
We found this trial at
Emile St
Omaha, Nebraska 68198
(402) 559-4000
Univ of Nebraska Med Ctr A vital enterprise in the nation’s heartland, the University of...
Omaha, NE
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