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Nab-Paclitaxel, Gemcitabine, and Hypofractionated Ablative Proton Therapy in Treating Patients with Locally Advanced Pancreatic Cancer

Trial Status: Active

This phase I trial studies the side effects and best dose of nab-paclitaxel and gemcitabine when given together with hypofractionated ablative proton beam radiation therapy in treating patients with pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced). Chemotherapy drugs, such as nab-paclitaxel and gemcitabine, 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. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving nab-paclitaxel, gemcitabine, and proton beam radiation therapy may work better in treating patients with pancreatic cancer.

Inclusion Criteria

  • Cytologic or histologic proof of adenocarcinoma of the pancreas.
  • Nonmetastatic pancreatic cancer. Metastatic disease includes spread to distant (non-regional) lymph nodes, organs, peritoneum and ascites.
  • Unequivocal radiographic findings contraindicating resection including, but not limited to, solid tumor contact with any of the following: 1) the superior mesenteric artery (SMA) > 180 degrees; 2) the celiac axis > 180 degrees; 3) the first jejunal superior mesenteric artery (SMA) branch; 4) unreconstructible superior mesenteric vein (SMV)/portal vein due to tumor involvement or occlusion; 5) the most proximal draining jejunal branch into the SMV. All patients should be evaluated at multidisciplinary tumor board for consensus.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Absolute neutrophil count >= 1,000/mm^3.
  • Platelet count >= 100,000/mm^3.
  • Creatinine =< 1.5 x upper limit of normal.
  • Calculated creatinine clearance > 45 mL/min.
  • Total bilirubin =< 2 mg/dL.

Exclusion Criteria

  • Patients with resectable or borderline resectable pancreatic cancer are ineligible.
  • No prior definitive resection of pancreatic cancer.
  • No prior radiation therapy to the abdomen that would overlap fields required in this study. Prior radiotherapy for other disease is allowed.
  • No prior chemotherapy except for FOLFIRINOX, Gem-Abrax, or Gem-Cap. A patient may be registered for the trial while undergoing chemotherapy.
  • Any grade 4 toxicity prior to start of chemoradiotherapy that may be due to induction chemotherapy.
  • Greater than 2 dose reductions during induction chemotherapy.
  • Chronic concomitant treatment with strong inhibitors of CYP3A4. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to the start of study treatment. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.
  • Baseline grade >= 2 neuropathy. Known Gilbert’s disease or known homozygosity for UGAT1A1*28 polymorphism.
  • Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14 days of study entry if they are in childbearing years/premenopausal.
  • Known human immunodeficiency virus (HIV)-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with gemcitabine and nab-paclitaxel. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  • Non-compliance with induction chemotherapy.

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: ACTIVE
Contact: Keith R. Unger
Phone: 202-444-3320

Maryland

Baltimore
Maryland Proton Treatment Center
Status: ACTIVE
Contact: Charles B. Simone
Phone: 410-369-5200
University of Maryland / Greenebaum Cancer Center
Status: ACTIVE
Contact: Jason K Molitoris
Phone: 410-328-6080

PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy for the treatment of locally advanced pancreatic cancer.

SECONDARY OBJECTIVES:

I. To evaluate and estimate primary tumor response in patients receiving the study regimen.

II. To evaluate and estimate the progression-free survival in patients receiving the study regimen.

III. To evaluate and estimate the median overall survival of patients with locally advanced pancreatic cancer receiving the study regimen.

IV. To determine the R0 resection rates in patients receiving the study regimen followed by surgery.

V. To assess the adverse events (AE) profile and safety of the study regimen.

VI. To assess patient reported quality of life impact from the study regimen.

OUTLINE: This is a dose-escalation study of gemcitabine and nab-paclitaxel.

INDUCTION PHASE: Patients receive oxaliplatin, irinotecan, leucovorin, and 5-fluorouracil (FOLFIRINOX), gemcitabine and nab-paclitaxel (Gem-Abrax), or gemcitabine and capecitabine (Gem-Cap), or a combination of these regimens over 2-3 months per institutional standards.

CONCURRENT PHASE: Patients receive gemcitabine intravenously (IV) over 30 minutes and nab-paclitaxel IV over 30-40 minutes on day 1 of each week of hypofractionated ablative proton beam radiation therapy in the absence of disease progression or unacceptable toxicity. Patients undergo hypofractionated ablative proton beam radiation therapy once daily (QD), 5 days a week for a total of 15 fractions.

After completion of study treatment, patients are followed up for 12 months.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Maryland / Greenebaum Cancer Center

Principal Investigator
Jason K Molitoris

  • Primary ID 1886GCC
  • Secondary IDs NCI-2018-03549, 1886GCCC, HP-00081403
  • Clinicaltrials.gov ID NCT03652428