Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

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

Hypofractionated Ablative Proton Therapy

Jason Molitoris, MD

Jasmine A Newman, BS

Nicole Villa, MSN, RN

Keith Unger, MD

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.

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).

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

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

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.

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

Time to recurrence and site of recurrence in patients with LAPC receiving preoperative concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy (RECIST)

Median overall survival of patients with LAPC receiving preoperative concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy

R0 resection rates in patients with LAPC receiving preoperative 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)

Patient reported quality of life impact from receiving preoperative concurrent nab-paclitaxel + gemcitabine combined with hypofractionated ablative proton therapy using the FACT-Hep questionnaire

Spots Global Cancer Trial Database for hypofractionated ablative proton therapy