Stereotactic Radiation, Nelfinavir Mesylate & Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Cancer

NCT01068327 | Completed Phase 1 FDA Drug

• 3 other identifiers: 0441-07-FBNCI-2009-01443P30CA036727
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of stereotactic radiation therapy and nelfinavir mesylate when given together with gemcitabine hydrochloride, leucovorin calcium, and fluorouracil in treating patients with locally advanced pancreatic cancer. Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Drugs, such as nelfinavir mesylate, may make tumor cells more sensitive to radiation therapy. 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 or by stopping them from dividing. Giving stereotactic radiation therapy and nelfinavir mesylate together with combination chemotherapy may kill more tumor cells.

Conditions

Adenocarcinoma of the Pancreas; Stage III Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0

  Due to delayed toxicities attributable to radiotherapy, all toxicities observed within 1 month of surgery will be scored. Toxicity will be graded and tabled by dose levels.

  Within 1 month of surgery

• Maximally tolerated dose (MTD) of stereotactic radiotherapy and concurrent nelfinavir mesylate

  The MTD of SRT/nelfinavir mesylate is defined as the highest dose level at which no greater than one dose-limiting toxicity is observed in 6 patients.

  3 patients will initially be treated at each dose level (4 levels); a minimum of 1 month of observation after surgery is required in all 3 patients before escalation

Secondary Outcomes (7)

• Rate of complete surgical resection

  At the time of surgery (2-3 weeks after completion of SRT)

• Pathological response

  Pre- to post-treatment

• Tumor response on CT/MRI

  Change from pre- to post-treatment

• Radiologic response and pathologic response

  Pre- to post-treatment

• Phospho-AKT expression in pancreatic tumor tissue (correlative)

  Pre- to post-nelfinavir mesylate

Study Arms (1)

Treatment (SRT, radiosensitizer, and chemotherapy)

EXPERIMENTAL

See Detailed Description

Drug: gemcitabine hydrochloride; Drug: leucovorin calcium; Drug: fluorouracil; Drug: nelfinavir mesylate; Radiation: stereotactic body radiation therapy; Radiation: hypofractionated radiation therapy; Procedure: therapeutic conventional surgery

Interventions

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Treatment (SRT, radiosensitizer, and chemotherapy)

leucovorin calcium DRUG

Given IV

Also known as: CF, CFR, LV

Treatment (SRT, radiosensitizer, and chemotherapy)

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Treatment (SRT, radiosensitizer, and chemotherapy)

nelfinavir mesylate DRUG

Given PO

Also known as: Viracept

Treatment (SRT, radiosensitizer, and chemotherapy)

stereotactic body radiation therapy RADIATION

Undergo radiotherapy

Also known as: SBRT, stereotactic radiation therapy, stereotactic radiotherapy

Treatment (SRT, radiosensitizer, and chemotherapy)

hypofractionated radiation therapy RADIATION

Undergo radiotherapy

Treatment (SRT, radiosensitizer, and chemotherapy)

therapeutic conventional surgery PROCEDURE

Undergo surgery

Treatment (SRT, radiosensitizer, and chemotherapy)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 metastases
• 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 field
• All patients must have radiographically assessable disease
• Patients must have a absolute granulocyte count (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

You may not qualify if:

• 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 human immunodeficiency virus (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 (nelfinavir mesylate)
• 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

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Related Publications (1)

• Lin C, Verma V, Ly QP, Lazenby A, Sasson A, Schwarz JK, Meza JL, Are C, Li S, Wang S, Hahn SM, Grem JL. Phase I trial of concurrent stereotactic body radiotherapy and nelfinavir for locally advanced borderline or unresectable pancreatic adenocarcinoma. Radiother Oncol. 2019 Mar;132:55-62. doi: 10.1016/j.radonc.2018.11.002. Epub 2018 Dec 20.

  PMID: 30825970 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Leucovorin; Fluorouracil; Nelfinavir; Radiosurgery

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Isoquinolines; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Chi Lin

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2010
• First Posted: February 12, 2010
• Study Start: November 5, 2007
• Primary Completion: August 1, 2013
• Study Completion: February 1, 2015
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

US (1)