Locally Advanced Pancreatic CancerPhase 1/2NCT03652428
Phase I Nab-Paclitaxel Plus Gemcitabine With Proton Therapy for Locally Advanced Pancreatic Cancer (LAPC)
A Phase 1/2 study testing Gemcitabine and Hypofractionated Ablative Proton Therapy in people with Locally Advanced Pancreatic Cancer, run by University of Maryland, Baltimore at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Locally Advanced Pancreatic Cancer
- What is being tested?
- Gemcitabine and Hypofractionated Ablative Proton Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 2 Apr 2019to 31 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Creatinine ≤1.5 × upper limit of normal
- Calculated creatinine clearance >45 mL/min
- Total bilirubin ≤2 mg/dL
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Maryland Medical Center/Maryland Proton Treatment Center
Baltimore, Maryland, 21201
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
About this study
Official title: 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.
Read the 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
- Being tested
- Gemcitabine, Hypofractionated Ablative Proton Therapy
- Keywords
- LAPC, Nab-paclitaxel +Gemcitabine, Proton Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called Nab-Paclitaxel
see arm description
Hypofractionated Ablative Proton TherapyRadiation
see arm description
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Gemcitabine; Radiation: Hypofractionated Ablative Proton Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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
Measured: Patients will be followed for 12 months after registration or until death, whichever occurs first.
Survival status (disease-free-survival vs. overall survival)
Time to recurrence and site of recurrence in patients with LAPC receiving preoperative concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy (RECIST)
Measured: Patients will be followed for 12 months after registration or until death, whichever occurs first.
Median Overall Survival of Patients
Median overall survival of patients with LAPC receiving preoperative concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy
Measured: Patients will be followed for 12 months after registration or until death, whichever occurs first.
R0 Resection
R0 resection rates in patients with LAPC receiving preoperative concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy
Measured: 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
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)
Measured: Patients will be followed for 12 months after registration or until death, whichever occurs first.
Quality of life through and after treatment
Patient reported quality of life impact from receiving preoperative concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy using the FACT-Hep questionnaire
Measured: Patients will be followed for 12 months after registration or until death, whichever occurs first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2018
- Study start2 Apr 2019
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Locally Advanced Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Department of Radiation Oncology, University of Maryland, Baltimore
- Investigators
- Jason Molitoris, MD, Principal investigator, University of Maryland/Maryland Proton Treatment Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03652428
- Sponsor's protocol ID
- HP-00081403
- Status last verified
- Aug 2026
- First submitted
- 22 Aug 2018
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 14758134Crane 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.
PubMed 11560155Krishnan 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.
PubMed 26972648
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Concurrent Nab-Paclitaxel + Gemcitabine With Hypofractionated, Ablative Proton Therapy for Locally Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT03652428
- Acronym / sponsor ID
- HP-00081403
- Conditions
- Locally Advanced Pancreatic Cancer
- Keywords
- LAPC, Nab-paclitaxel +Gemcitabine, Proton Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 2 Apr 2019 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 29 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pancreatic Proton Therapy With Concurrent Gem + Nab-paclitaxel | Other | Drug: Gemcitabine, Radiation: Hypofractionated Ablative Proton TherapyPart 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GemcitabineAlso: Nab-Paclitaxelsee arm description | Drug | Pancreatic Proton Therapy With Concurrent Gem + Nab-paclitaxel |
| Hypofractionated Ablative Proton Therapysee arm description | Radiation | Pancreatic Proton Therapy With Concurrent Gem + Nab-paclitaxel |
Primary outcome
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.
6 secondary outcomes
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.
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.
Median Overall Survival of Patients
Time frame: 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.
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.
Quality of life through and after treatment
Time frame: Patients will be followed for 12 months after registration or until death, whichever occurs first.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Background: PubMed 14758134Rich 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.
- Background: PubMed 11560155Crane 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.
- Background: PubMed 26972648Krishnan 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.
Related trials for Locally Advanced Pancreatic Cancer
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
CREO - Microwave Ablation Feasibility Study
Pancreatic Cancer, Liver Cancer (Locally Advanced or Metastatic)
RecruitingPhase 1
Radiotherapy in Combination With TTI-101 in Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer
Active, not recruitingPhase 1/2
Testing the Addition of a New Anti-cancer Drug, M3814 (Peposertib), to the Usual Radiotherapy in Patients With Locally Advanced Pancreatic Cancer
Locally Advanced Pancreatic Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8
Active, not recruitingPhase 2
Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Molitoris, MD principal investigator
University of Maryland/Maryland Proton Treatment Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Gemcitabine and Hypofractionated Ablative Proton Therapy in people with Locally Advanced Pancreatic Cancer, run by University of Maryland, Baltimore at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03652428, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.