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

March 5, 2024 updated by: Department of Radiation Oncology, University of Maryland, Baltimore

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The investigators propose a phase I trial to determine the maximum tolerable dose (MTD) and the recommended dose for phase II (RP2D) of concurrent nab-paclitaxel + gemcitabine in combination with ablative IMPT delivered as a fixed dose of 67.5 Gy in 15 fractions daily fractions with 5 fractions per week. In contrast to prior pancreatic cancer studies of chemoradiotherapy which utilized photon RT to treat gross disease and elective lymph nodes (1,2) the proposed study is hypothesized to reduce toxicity risk by limiting highly conformal IMPT to the gross tumor volume. Furthermore, to increase the margin of safety in a manner similar to published data from MDACC (3), the high dose region will be limited to areas at least 5 mm from nearby GI structures (duodenum, small bowel, stomach, etc.). Regions within this area will be treated only to 37.5 Gy in 15 fractions. This dose limitation is also important given that paclitaxel, in addition to increasing systemic efficacy, is a known radiosensitizer (1).

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • MedStar Georgetown University Hospital
        • Contact:
        • Principal Investigator:
          • Keith Unger, MD
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland Medical Center/Maryland Proton Treatment Center
        • Principal Investigator:
          • Jason Molitoris, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Pancreatic Proton Therapy With Concurrent Gem + Nab-paclitaxel

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
see arm description
Other Names:
  • Nab-Paclitaxel
Radiation: Hypofractionated Ablative Proton Therapy
see arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose of Gemcitabine and nab-Paclitaxel in LAPC patients receiving proton therapy
Time Frame: Patients will be followed for 12 months after registration or until death, whichever occurs first.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Tumor Response in LAPC patients receiving proton therapy with concurrent Gemcitabine and nab-Paclitaxel
Time Frame: Patients will be followed for 12 months after registration or until death, whichever occurs first.
Primary tumor response in patients receiving with LAPC receiving preoperative concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy evaluated by CT or MRI
Patients will be followed for 12 months after registration or until death, whichever occurs first.
Survival status (disease-free-survival vs. overall survival)
Time Frame: Patients will be followed for 12 months after registration or until death, whichever occurs first.
Time to recurrence and site of recurrence in patients with LAPC receiving preoperative concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy (RECIST)
Patients will be followed for 12 months after registration or until death, whichever occurs first.
Median Overall Survival of Patients
Time Frame: Patients will be followed for 12 months after registration or until death, whichever occurs first.
Median overall survival of patients with LAPC receiving preoperative 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.
R0 Resection
Time Frame: Patients will be followed for 12 months after registration or until death, whichever occurs first.
R0 resection rates in patients with LAPC receiving preoperative 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.
Number of adverse events/toxicites reported during and following treatment of concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy
Time Frame: Patients will be followed for 12 months after registration or until death, whichever occurs first.
Number of toxicities participants reported by participants during and following treatment of concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy (NIH CTCAE v 4)
Patients will be followed for 12 months after registration or until death, whichever occurs first.
Quality of life through and after treatment
Time Frame: Patients will be followed for 12 months after registration or until death, whichever occurs first.
Patient reported quality of life impact from receiving preoperative concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy using the FACT-Hep questionnaire
Patients will be followed for 12 months after registration or until death, whichever occurs first.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Investigators

  • Principal Investigator: Jason Molitoris, MD, University of Maryland/Maryland Proton Treatment Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 2, 2019

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

August 22, 2018

First Submitted That Met QC Criteria

August 28, 2018

First Posted (Actual)

August 29, 2018

Study Record Updates

Last Update Posted (Estimated)

March 6, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00081403

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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