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

Alternate Title

Stereotactic Radiation Therapy, Nelfinavir, Gemcitabine, Leucovorin, and Fluorouracil in Treating Patients With Locally Advanced Pancreatic Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active 19 and over NCI UNMC-44107 441-07, UNMC-441-07-FB, NCT00705393

Objectives

Primary

1. To establish the safety, dose-limiting toxicities, and maximum tolerated dose of hypofractionated stereotactic radiotherapy and concurrent nelfinavir when administered in combination with gemcitabine hydrochloride, leucovorin calcium, and fluorouracil as neoadjuvant therapy in patients with locally advanced pancreatic cancer.

Secondary

1. To evaluate the complete surgical resection rate in patients treated with this regimen.
2. To evaluate the pathological response in patients treated with this regimen.
3. To evaluate tumor response by CT scan or MRI in these patients.
4. To correlate radiologic response with pathologic response in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Pathologically confirmed adenocarcinoma of the pancreas
  • Locally advanced disease
  • Maximum dimension of the tumor ≤ 8 cm



• Radiographically assessable disease



• All malignant disease must be encompassable within a single irradiation field
  • Prior radiotherapy field must not overlap with the 20% isodose line of the current radiotherapy field



• Patients with biliary* or gastroduodenal obstruction are eligible provided drainage or surgical bypass was performed prior to initiation of study treatment

   [Note: *Patients with biliary obstruction must undergo biliary decompression either through endoscopic placement of a biliary stent or percutaneous transhepatic drainage.]




• No distant metastases

Prior/Concurrent Therapy:

• No prior multiple abdominal surgeries unless the patient has a common bile duct stent adjacent to the tumor that may be used as an internal marker
• No prior chemotherapy for pancreatic cancer
• No prior radiotherapy to the abdomen
• More than 5 years since prior chemotherapy or radiotherapy for other malignancies
• More than 1 month since prior and no other concurrent investigational agents
• No concurrent drugs that are contraindicated with nelfinavir, including any of the following:
  • Amiodarone
  • Quinidine
  • Rifampin
  • Dihydroergotamine
  • Ergonovine
  • Ergotamine
  • Methylergonovine
  • Hypericum perforatum (St. John's wort)
  • Lovastatin
  • Simvastatin
  • Pimozide
  • Midazolam
  • Triazolam
• No other concurrent anticancer agents

Patient Characteristics:

• Karnofsky performance status 60-100%
• ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Serum creatinine ≤ 2 mg/dL
• Total bilirubin ≤ 2.0 mg/dL (in the absence of biliary obstruction) OR < 4.0 mg/dL (in the presence of biliary obstruction)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to take oral medications
• Able to undergo staging laparoscopy and marker implantation (e.g., gold clip, surgical clip, or a common bile duct stent adjacent to the tumor)
• No history of allergy to chemotherapy agents or to antiemetics appropriate for administration in conjunction with study-directed chemotherapy
• No concurrent uncontrolled illness (e.g., ongoing or active infection requiring IV 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 study with reasonable safety
• No other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinoma
• No active duodenal ulcer or bleeding
• No history of gastrointestinal fistula, perforation, or other significant bowel problem (i.e., severe nausea, vomiting, inflammatory bowel disease, or significant bowel resection)
• No HIV infection
• No hepatic insufficiency

Expected Enrollment

Outcomes

Dose-limiting toxicity as assessed by NCI CTCAE v3.0
Maximum tolerated dose of stereotactic radiotherapy and concurrent nelfinavir

Rate of complete surgical resection
Pathological response
Association between standardized uptake value (SUV) changes on PET scans and pathological response

Outline

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. 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 1-2 weeks later. Approximately 1 month after surgery, these patients receive three additional courses of gemcitabine, 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, 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.

Trial Contact Information

Trial Lead Organizations

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Chi Lin, MD, PhD, Principal investigator		Ph: 402-559-4238 Email: clin@unmc.edu

U.S.A.
Nebraska
	Omaha
	UNMC Eppley Cancer Center at the University of Nebraska Medical Center
		Clinical Trials Office - UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Ph:  800-999-5465

Registry Information
Official Title		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
Trial Start Date		2007-11-05
Trial Completion Date		2017-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00705393
Date Submitted to PDQ		2008-06-12
Information Last Verified		2008-06-24
NCI Grant/Contract Number		CA36727