Combining chemotherapy and proton therapy for advanced pancreatic cancer

Phase I Study of Concurrent Nab-Paclitaxel + Gemcitabine With Hypofractionated, Ablative Proton Therapy for Locally Advanced Pancreatic Cancer

This study is testing how much of the chemotherapy drugs nab-paclitaxel and gemcitabine can be safely combined with proton therapy to help people with advanced pancreatic cancer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: University of Maryland, Baltimore (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 2 sites (Washington D.C., District of Columbia and 1 other locations)
• Trial ID: NCT03652428 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine the maximum tolerated dose of the chemotherapy drugs nab-paclitaxel and gemcitabine when used alongside hypofractionated ablative proton therapy for patients with locally advanced pancreatic cancer. Participants will receive proton therapy daily for three weeks, along with chemotherapy administered weekly during this period. The study seeks to minimize toxicity by precisely targeting the tumor while sparing surrounding healthy tissues. The trial will also establish a recommended dose for future phases based on the findings.

Who should consider this trial

Good fit: Ideal candidates include individuals with nonmetastatic adenocarcinoma of the pancreas who are not eligible for surgical resection.

Not a fit: Patients with resectable or borderline resectable pancreatic cancer will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and reduce side effects for patients with locally advanced pancreatic cancer.

How similar studies have performed: While there have been studies on chemoradiotherapy for pancreatic cancer, this specific combination of nab-paclitaxel, gemcitabine, and proton therapy is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Cytologic or histologic proof of adenocarcinoma of the pancreas.
2. Nonmetastatic pancreatic cancer. Metastatic disease includes spread to distant (non-regional) lymph nodes, organs, peritoneum and ascites.
3. Unequivocal radiographic findings contraindicating resection including, but not limited to, solid tumor contact with any of the following: 1) the SMA \>180º; 2) the celiac axis \>180º; 3) the first jejunal superior mesenteric artery (SMA) branch; 4) unreconstructible superior mesenteric vein (SMV)/portal vein due to tumor involvement or occclusion; 5) the most proximal draining jejunal branch into the SMV.
4. ECOG Performance Status 0 or 1.
5. Absolute neutrophil count ≥1,000/mm3
6. Platelet count ≥100,000/mm3
7. Creatinine ≤1.5 × upper limit of normal
8. Calculated creatinine clearance \>45 mL/min
9. Total bilirubin ≤2 mg/dL

Exclusion Criteria:

1. Patients with resectable or borderline resectable pancreatic cancer are ineligible.
2. No prior definitive resection of pancreatic cancer.
3. No prior radiation therapy to the abdomen that would overlap fields required in this study. Prior radiotherapy for other disease is allowed.
4. No prior chemotherapy except for FOLFIRINOX, Gem-Abrax, or Gem-Cap. A patient may be registered for the trial while undergoing chemotherapy.
5. Any grade 4 toxicity prior to start of chemoradiotherapy that may be due to induction chemotherapy.
6. Greater than 2 dose reductions during induction chemotherapy.
7. 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.
8. Baseline Grade ≥ 2 neuropathy. Known Gilbert's disease or known homozygosity for UGAT1A1\*28 polymorphism.
9. Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14 days of study entry if they are in childbearing years/premenopausal.
10. Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with gemcitabine and nab-paclitaxel.
11. Non-compliance with induction chemotherapy.

Where this trial is running

Washington D.C., District of Columbia and 1 other locations

• MedStar Georgetown University Hospital — Washington D.C., District of Columbia, United States (Recruiting)
• University of Maryland Medical Center/Maryland Proton Treatment Center — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Jason Molitoris, MD — University of Maryland/Maryland Proton Treatment Center
• Study coordinator: Jason Molitoris, MD

Conditions Locally Advanced Pancreatic Cancer; LAPC; Nab-paclitaxel +Gemcitabine; Proton Therapy