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

NCT01959672 | Completed Phase 2 Results DMC FDA Drug

• 5 other identifiers: 0441-13-FBNCI-2013-02273NCI-2013-02118NCI-2012-00835P30CA036727
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma; Stage I Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Progressive Disease,

  Rate of progressive disease defined as at least a 25% increase in the longest diameter of a lesion, taking as reference the longest diameter recorded since the treatment started. An exact one-sided 90% confidence interval will be constructed round the progressive disease rate.

  Up to 4 months

Secondary Outcomes (4)

• Distant Failure-free Survival

  Date of administration study drug to the date of first appearance of tumor lesions by imaging, or death, assessed up to 5 years

• Overall Survival

  Date of first of study drug to the date of death, assessed up to 5 years

• Surgical Complete Resection (Negative Margin) Rate

  Up to week 18

• Tumor Response Rate, Evaluated on the Pathology Specimen

  Up to week 18

Other Outcomes (1)

• Number of Participants With CA-125-Specific T-cell Signal.

  Baseline to up to week 12

Study Arms (1)

Treatment (chemotherapy, oregovomab, SBRT, surgery)

EXPERIMENTAL

CHEMOTHERAPY: Patients receive gemcitabine hydrochloride 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 PO 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.

Procedure: 4-Dimensional Computed Tomography; Drug: Fluorouracil; Drug: Gemcitabine Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Nelfinavir Mesylate; Biological: Oregovomab; Radiation: Stereotactic Body Radiation Therapy; Procedure: Therapeutic Conventional Surgery

Interventions

4-Dimensional Computed Tomography PROCEDURE

Correlative studies

Also known as: 4D Computed Tomography, 4DCT, Time-Resolved CT Data Acquisition

Treatment (chemotherapy, oregovomab, SBRT, surgery)

Fluorouracil DRUG

Given IV

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (chemotherapy, oregovomab, SBRT, surgery)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011

Treatment (chemotherapy, oregovomab, SBRT, surgery)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemotherapy, oregovomab, SBRT, surgery)

Leucovorin Calcium DRUG

Given IV

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (chemotherapy, oregovomab, SBRT, surgery)

Nelfinavir Mesylate DRUG

Given PO

Also known as: AG1343, Viracept

Treatment (chemotherapy, oregovomab, SBRT, surgery)

Oregovomab BIOLOGICAL

Given IV

Also known as: B43.13, MoAb B43.13, Monoclonal Antibody B43.13, OvaRex, OvaRex Monoclonal Antibody B43.13

Treatment (chemotherapy, oregovomab, SBRT, surgery)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SBRT

Treatment (chemotherapy, oregovomab, SBRT, surgery)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgical resection

Treatment (chemotherapy, oregovomab, SBRT, surgery)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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 therapy
• 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 insufficiency
• 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 dysgammaglobulinemia
• 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

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

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Fluorouracil; dehydroftorafur; Gemcitabine; Leucovorin; Nelfinavir; oregovomab; 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)

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

Results Point of Contact

• Title: Chi Lin
• Organization: University of Nebraska Medical Center

clin@unmc.edu

402-552-3844

Study Officials

• Chi Lin

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2013
• First Posted: October 10, 2013
• Study Start: September 6, 2013
• Primary Completion: April 1, 2018
• Study Completion: December 1, 2018
• Last Updated: October 10, 2023
• Results First Posted: November 15, 2019

Record last verified: 2020-02

Locations

US (1)