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Locally Advanced Pancreatic Cancer (LAPC) (GCC 1886)

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ClinicalTrials.gov Identifier: NCT03652428
Recruitment Status : Recruiting
First Posted : August 29, 2018
Last Update Posted : December 24, 2018
Sponsor:
Information provided by (Responsible Party):
Department of Radiation Oncology, University of Maryland

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.

Condition or disease Intervention/treatment Phase
Locally Advanced Pancreatic Cancer Drug: Gemcitabine Radiation: Hypofractionated Ablative Proton Therapy Phase 1 Phase 2

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  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Concurrent Nab-Paclitaxel + Gemcitabine With Hypofractionated, Ablative Proton Therapy for Locally Advanced Pancreatic Cancer
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: Nab-Paclitaxel

Radiation: Hypofractionated Ablative Proton Therapy
see arm description




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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)

  3. 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

  4. 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

  5. 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)

  6. 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



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03652428


Contacts
Contact: Adeel Kaiser, MD 410-328-2328 adeelkaiser@umm.edu
Contact: Chad Burleson, MPH 410-328-8018 chad.burleson@umm.edu

Locations
United States, Maryland
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Chad Burleson, MPH    410-328-8018    chad.burleson@umm.edu   
Principal Investigator: Adeel Kaiser, MD         
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Adeel Kaiser, MD University of Maryland/Maryland Proton Treatment Center

Publications:
Responsible Party: Department of Radiation Oncology, Principal Investigator, University of Maryland
ClinicalTrials.gov Identifier: NCT03652428     History of Changes
Other Study ID Numbers: HP-00081403
First Posted: August 29, 2018    Key Record Dates
Last Update Posted: December 24, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Department of Radiation Oncology, University of Maryland:
LAPC
Nab-paclitaxel +Gemcitabine
Proton Therapy

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs