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

NCT ID: NCT03652428

Last Updated: 2025-03-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-02
• Study Completion Date: 2026-12-31

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.

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).

Conditions

Locally Advanced Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: OTHER

Gemcitabine

Intervention Type: DRUG

see arm description

Hypofractionated Ablative Proton Therapy

Intervention Type: RADIATION

see arm description

Interventions

Gemcitabine

see arm description

Intervention Type: DRUG

Hypofractionated Ablative Proton Therapy

see arm description

Intervention Type: RADIATION

Other Intervention Names

Nab-Paclitaxel

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Department of Radiation Oncology

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jason Molitoris, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland/Maryland Proton Treatment Center

Locations

MedStar Georgetown University Hospital

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

Site Status: RECRUITING

University of Maryland Medical Center/Maryland Proton Treatment Center

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jason Molitoris, MD

Role: CONTACT

jmolitoris@umm.edu

410-328-2328

Jasmine A Newman, BS

Role: CONTACT

jasmine.newman@umm.edu

410-369-5355

Facility Contacts

Nicole Villa, MSN, RN

Role: primary

nv209@georgetown.edu

202-687-2939

Jasmine A Newman, BS

Role: primary

jasmine.newman@umm.edu

410-369-5355

References

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.

Reference Type: BACKGROUND

PMID: 14758134 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11560155 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26972648 (View on PubMed)

Other Identifiers

HP-00081403

Identifier Type: -

Identifier Source: org_study_id