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
PRIMARY OBJECTIVES:
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
regimen.
SECONDARY OBJECTIVES:
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.
TERTIARY OBJECTIVES:
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)
OUTLINE:
This is a dose-escalation study of stereotactic radiotherapy (SRT) and concurrent nelfinavir
mesylate.
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
11.
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.
Interventional
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity as assessed by NCI CTCAE v3.0
Ongoing throughout treatment
Yes
Chi Lin
Principal Investigator
University of Nebraska
United States: Institutional Review Board
441-07
NCT01068327
November 2007
Name | Location |
---|---|
UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha, Nebraska 68198-7680 |