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A Phase 1 Study of Hypofractionated Stereotactic Radiotherapy and Concurrent HIV Protease Inhibitor Nelfinavir as Part of a Neoadjuvant Regimen in Patients With Locally Advanced Pancreatic Cancer

Phase 1
19 Years
Open (Enrolling)
Adenocarcinoma of the Pancreas, Pancreatic Cancer, Stage III Pancreatic Cancer

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Trial Information

A Phase 1 Study of Hypofractionated Stereotactic Radiotherapy and Concurrent HIV Protease Inhibitor Nelfinavir as Part of a Neoadjuvant Regimen in Patients With Locally Advanced Pancreatic Cancer


I. To establish the safety, dose-limiting toxicities and maximally tolerated dose of
hypofractionated stereotactic radiotherapy concurrently with nelfinavir in patients with
locally advanced pancreatic cancer given as part of a neoadjuvant chemoradiation therapy


I. To evaluate the surgical complete resection rate. II. To evaluate the pathological
response. III. To evaluate tumor response on CT/MRI. IV. To evaluate the correlation between
the radiologic response and pathologic response.


I. To measure phospho-AKT expression in pancreatic tumor tissue prior to and following the
neoadjuvant chemo-radiation program. (Correlative) II. To measure nelfinavir
pharmacokinetics at steady-state. (Correlative) III. To measure the pharmacogenomic status
of CYP2C19*2 (G681A) in the study population. (Correlative)


This is a dose-escalation study of stereotactic radiotherapy (SRT) and concurrent nelfinavir

NEOADJUVANT THERAPY: Patients receive gemcitabine hydrochloride IV over 30 minutes,
leucovorin calcium IV over 30 minutes, and fluorouracil (5-FU) IV continuously over 24 hours
on days 1 and 8. Treatment repeats every 3 weeks for up to 3 courses in the absence of
disease progression or unacceptable toxicity. Patients then receive oral nelfinavir mesylate
twice daily beginning in week 9 and continuing until the completion of SRT or until 14 days
after the completion of SRT. Patients undergo concurrent SRT once daily for 5 days in week

SURGERY AND ADJUVANT CHEMOTHERAPY: Approximately 2-3 weeks after completion of SRT, patients
undergo restaging to evaluate disease response. Patients with resectable or potentially
resectable disease and no metastasis undergo definitive surgery 2-3 weeks later.
Approximately 1 month after surgery, these patients receive three additional courses of
gemcitabine hydrochloride, leucovorin calcium, and 5-FU as above. Patients with unresectable
disease that is stable or responsive at the time of surgical exploration may resume
treatment with gemcitabine hydrochloride, leucovorin calcium, and 5-FU as above in the
absence of disease progression or unacceptable toxicity. Patients with metastatic disease at
the time of restaging are removed from the study.

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

Inclusion Criteria:

- The time between other investigational agents and enrollment on this study is at
least 30 days

- Pathologically confirmed adenocarcinoma of the pancreas

- Patients have localized or locally advanced disease with no evidence of distant

- The maximum dimension of the tumor must be =< 8 cm

- Karnofsky Performance Status of 60% or better

- Patients with biliary or gastroduodenal obstruction must have drainage or surgical
bypass prior to starting chemoradiation

- 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

- All patients must have radiographically assessable disease

- Patients must have a AGC greater than or equal to 1500/uL and platelet count greater
than or equal to 100,000/uL

- Patients must have a serum creatinine less than or equal to 2 mg/dL and 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

- 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

- Any prior therapy is acceptable except radiation to the abdomen

Exclusion Criteria:

- Patients receiving the following drugs will be clinically evaluated as to whether
dosage/medication can be changed to permit patient on study: carbamazepine;
phenobarbital; phenytoin; rifabutin; sildenafil; atorvastatin; cyclosporine;
tacrolimus; sirolimus; methadone; ethinyl estradiol; azithromycin

- Patients who can not undergo staging laparoscopy and marker implantation; 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

- History of allergy to chemotherapy agents or to antiemetics appropriate for
administration in conjunction with protocol-directed chemotherapy

- 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 chemotherapy program outlined in
this protocol with reasonable safety

- Patients with HIV infection, or hepatic insufficiency

- Patients may not be receiving or have received any other investigational agents
during/or within 1 month prior to treatment with NFV

- Patients who can not take oral medications

- 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 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 receiving the following drugs that are contraindicated with NFV will be
excluded: amiodarone; quinidine; rifampin; dihydroergotamine; ergonovine; ergotamine;
methylergonovine; St. John's wort (hypericum perforatum); lovastatin; simvastatin;
pimozide; midazolam; triazolam

- Pregnant and nursing women are excluded from this study

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity as assessed by NCI CTCAE v3.0

Outcome Time Frame:

Ongoing throughout treatment

Safety Issue:


Principal Investigator

Chi Lin

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Nebraska


United States: Institutional Review Board

Study ID:




Start Date:

November 2007

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Pancreas
  • Pancreatic Cancer
  • Stage III Pancreatic Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Pancreatic Neoplasms



UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680