Phase I Nab-Paclitaxel Plus Gemcitabine With Proton Therapy for Locally Advanced Pancreatic Cancer (LAPC)

NCT03652428 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HP-00081403
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the maximum tolerated dose of the chemotherapy drugs nab-paclitaxel and gemcitabine when combined with hypofractionated ablative proton therapy for the treatment of locally advanced pancreatic cancer. You will receive proton therapy once a day (Monday - Friday) for 3 weeks. Participants will also receive chemotherapy on each Monday of those three weeks.

Conditions

Locally Advanced Pancreatic Cancer

Keywords

LAPC; Nab-paclitaxel +Gemcitabine; Proton Therapy

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of Gemcitabine and nab-Paclitaxel in LAPC patients receiving proton therapy

  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.

  Patients will be followed for 12 months after registration or until death, whichever occurs first.

Secondary Outcomes (6)

• Primary Tumor Response in LAPC patients receiving proton therapy with concurrent Gemcitabine and nab-Paclitaxel

  Patients will be followed for 12 months after registration or until death, whichever occurs first.

• Survival status (disease-free-survival vs. overall survival)

  Patients will be followed for 12 months after registration or until death, whichever occurs first.

• Median Overall Survival of Patients

  Patients will be followed for 12 months after registration or until death, whichever occurs first.

• R0 Resection

  Patients will be followed for 12 months after registration or until death, whichever occurs first.

• Number of adverse events/toxicites reported during and following treatment of concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy

  Patients will be followed for 12 months after registration or until death, whichever occurs first.

Study Arms (1)

Pancreatic Proton Therapy With Concurrent Gem + Nab-paclitaxel

OTHER

Part I: Gemcitabine + nab-paclitaxel: • Administered per institutional standard every 7 days for 3 weeks Part II: Hypofractionated ablative pancreatic proton radiation therapy 67.5 Gy fractions once per day Monday - Friday for 3 weeks, for a total of 15 fractions. Part III: Surgery, if resectable, then adjuvant chemo per discretion of MD or no further therapy OR Chemo per discretion of MD if not resectable

Drug: Gemcitabine; Radiation: Hypofractionated Ablative Proton Therapy

Interventions

Hypofractionated Ablative Proton Therapy RADIATION

see arm description

Pancreatic Proton Therapy With Concurrent Gem + Nab-paclitaxel

Gemcitabine DRUG

see arm description

Also known as: Nab-Paclitaxel

Pancreatic Proton Therapy With Concurrent Gem + Nab-paclitaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• ECOG Performance Status 0 or 1.
• Absolute neutrophil count ≥1,000/mm3
• Platelet count ≥100,000/mm3
• Creatinine ≤1.5 × upper limit of normal
• Calculated creatinine clearance \>45 mL/min
• Total bilirubin ≤2 mg/dL

You may not qualify if:

• 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 HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with gemcitabine and nab-paclitaxel.
• Non-compliance with induction chemotherapy.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (2)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

University of Maryland Medical Center/Maryland Proton Treatment Center

Baltimore, Maryland, 21201, United States

RECRUITING

Related Publications (3)

• Rich T, Harris J, Abrams R, Erickson B, Doherty M, Paradelo J, Small W Jr, Safran H, Wanebo HJ. Phase II study of external irradiation and weekly paclitaxel for nonmetastatic, unresectable pancreatic cancer: RTOG-98-12. Am J Clin Oncol. 2004 Feb;27(1):51-6. doi: 10.1097/01.coc.0000046300.88847.bf.

  PMID: 14758134 BACKGROUND

• Crane CH, Janjan NA, Evans DB, Wolff RA, Ballo MT, Milas L, Mason K, Charnsangavej C, Pisters PW, Lee JE, Lenzi R, Vauthey JN, Wong A, Phan T, Nguyen Q, Abbruzzese JL. Toxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer. Int J Pancreatol. 2001;29(1):9-18. doi: 10.1385/IJGC:29:1:09.

  PMID: 11560155 BACKGROUND

• Krishnan S, Chadha AS, Suh Y, Chen HC, Rao A, Das P, Minsky BD, Mahmood U, Delclos ME, Sawakuchi GO, Beddar S, Katz MH, Fleming JB, Javle MM, Varadhachary GR, Wolff RA, Crane CH. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation. Int J Radiat Oncol Biol Phys. 2016 Mar 15;94(4):755-65. doi: 10.1016/j.ijrobp.2015.12.003. Epub 2015 Dec 11.

  PMID: 26972648 BACKGROUND

MeSH Terms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Jason Molitoris, MD

  University of Maryland/Maryland Proton Treatment Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason Molitoris, MD

CONTACT

410-328-2328; jmolitoris@umm.edu

Jasmine A Newman, BS

CONTACT

410-369-5355; jasmine.newman@umm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: August 29, 2018
• Study Start: April 2, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (2)