Study of Proton Therapy in Adjuvant Pancreatic Cancer (Proton-PANC)

Phase I Study of Proton Therapy in Adjuvant Pancreatic Cancer (Proton-PANC)

This trial aims to determine a safe schedule of short-course proton beam radiation therapy with adjuvant mFOLFIRINOX for patients with resected pancreatic adenocarcinoma.

Study Overview

• Status: Recruiting
• Conditions: Resected Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: mFOLFIRINOX; Radiation: Proton beam radiation

Detailed Description

The investigators hypothesize that resected pancreatic cancer patients will benefit from enhanced local control with the addition of radiation therapy to adjuvant FFX. The recently reported PRODIGE 24 study, demonstrated that 12 cycles of adjuvant FFX without radiation therapy significantly improved survival and time to metastatic failure rates as compared to GEM alone. Excessive distant failures rates using prior adjuvant systemic therapies, may have limited the impact of radiation therapy; therefore, improvements in systemic control can increase the benefit of local control.

In this study, the investigators utilize 5 fraction PRT, delivered over 1 week, during adjuvant FFX (between cycles 6 and 7) to minimize the interruptions in chemotherapy as well as to reduce the length of time from surgical resection to initiating adjuvant radiation therapy. Conventional radiation therapy is typically delivered over 5 weeks and is commonly given after the completion of adjuvant chemotherapy. Conventional radiation therapy cannot be given concurrently with FFX due to the synergistic toxicities. In contrast, PRT significantly reduces the exposure of normal tissues to the effects of radiation therapy and has been safely delivered using a 5 fraction schedule with chemotherapy, as previously discussed.

Chemotherapy will consist of mFOLFIRINOX in 14-day cycles x 12 as used in the PRODIGE 24 study:

• Irinotecan 150 mg/m2 IV day 1
• Oxaliplatin 85 mg/m2 IV day 1
• Leucovorin 400 mg/m2 IV day 1
• 5-fluorouracil 2,400 mg/m2 IV days 1-3 (no bolus)
• Pegfilgrastim 6 mg SC on-body injector day 3 (optional, up to investigator's discretion, can alternatively do day 4 without on-body injector)
• Suggested supportive care medications: fosaprepitant 150 mg IV day 1, dexamethasone 12 mg IV day 1, ondansetron 16 mg IV day 1, dexamethasone 4 mg PO q AM days 2-3, ondansetron 8 mg PO BID days 2-3.
• Dose adjustments will be permitted at the discretion of the treating oncologist based on patients' prior tolerability to FFX
• Proton radiation will consistent of 5 daily doses of 5 GyE total, ideally administered Monday through Friday but can be administered within 7 business days, between cycles 6 and 7

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Recruiting
      • Georgetown University Medical Center - Lombardi Comprehensive Cancer Center
      • Contact: Benjamin Weinberg, MD; Phone Number: 202-444-2223; Email: baw12@gunet.georgetown.edu
      • Sub-Investigator: John Marshall, MD
      • Sub-Investigator: Ruth He, MD, PhD
      • Sub-Investigator: Louis Weiner, MD
      • Sub-Investigator: Keith Unger, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Undergone pancreaticoduodenectomy with curative intent
• Pathologically-confirmed pancreatic adenocarcinoma of the pancreatic head (adenocarcinoma must be the predominant component of the histology)
• Completed 2 cycles of adjuvant chemotherapy composed of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan
• Complete resection (R0) or resection with microscopic positive magins (R1)
• Adequate healing post-operatively
• Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥ 100 × 109/L; hemoglobin ≥ 9.0 g/dL. Patients may have a transfusion of red blood cells to meet the hemoglobin requirement.
• Renal function: serum creatinine ≤ 1.5 × upper normal limit of institution's normal range or creatinine clearance ≥ 30 mL/min for subjects with creatinine levels above institutional normal
• Hepatic function: AST and ALT ≤ 3.0 × the upper normal limit of institution's normal range. Total bilirubin ≤ 1.5 × the upper normal limit of institution's normal range.
• Partial Thromboplastin Time (PTT) must be ≤ 1.5 × upper normal limit of institution's normal range and INR (International Normalized Ratio) < 1.5. Subjects on anticoagulant (such as warfarin) will be permitted to enroll as long as the INR is in the acceptable therapeutic range as determined by the investigator.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
• Prior neoadjuvant chemotherapy is alllowed
• Patients must have fully recovered from all effects of surgery. Patients must have had at least two weeks after minor surgery and four weeks after major surgery before starting therapy. Minor procedures requiring "Twilight" sedation such as endoscopies or mediport placement may only require a 24-hour waiting period, but this must be discussed with an investigator.
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
• Patient is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by the Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures

Exclusion Criteria:

• Ampullary adenocarcinoma
• Women who are pregnant or breastfeeding
• Macroscopic positive margins (R2) or evidence of residual local or metastatic disease
• Resection not including pancreaticoduodenectomy
• Known allergy or intolerance to leucovorin, 5-fluorouracil, oxaliplatin, or irinotecan
• Prior radiation to the upper abdomen
• Inability to swallow pills or bowel obstruction
• Any invasive cancer in the previous 3 years requiring chemotherapy, radiation, or anticancer therapy following surgery
• Insurance unwilling to pre-authorize PRT, FFX, and (if necessary) pegfilgrastim
• Clinically significant liver disease (Patients with resolved hepatitis B infection are eligible if HBsAg testing is negative; Patients with resolved hepatitis C infection are eligible if viral RNA PCR is negative)
• Uncontrolled HIV infection (CD4 count must be at least 200 and viral load undectable on a stable antiretroviral regimen to be eligible for enrollment)
• Major surgery within 4 weeks prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; mFOLFIRINOX + Proton beam radiation Radiation given on days 8-12 of cycle 6	Drug: mFOLFIRINOX; Chemotherapy will consist of mFOLFIRINOX in 14-day cycles x 12 as used in the PRODIGE 24 study: Irinotecan 150 mg/m2 IV day 1; Oxaliplatin 85 mg/m2 IV day 1; Leucovorin 400 mg/m2 IV day 1; 5-fluorouracil 2,400 mg/m2 IV days 1-3 (no bolus); Pegfilgrastim 6 mg SC on-body injector day 3 (optional, up to investigator's discretion, can alternatively do day 4 without on-body injector); Suggested supportive care medications: fosaprepitant 150 mg IV day 1, dexamethasone 12 mg IV day 1, ondansetron 16 mg IV day 1, dexamethasone 4 mg PO q AM days 2-3, ondansetron 8 mg PO BID days 2-3.; Radiation: Proton beam radiation; Proton beam radiation will consist of 5 daily doses of 5 GyE total, ideally administered Monday through Friday but can be administered within 7 business days, between cycles 6 and 7
Experimental: Dose Level 2; mFOLFIRINOX + Proton beam radiation Radiation given on days 15-19 of cycle 6	Drug: mFOLFIRINOX; Chemotherapy will consist of mFOLFIRINOX in 14-day cycles x 12 as used in the PRODIGE 24 study: Irinotecan 150 mg/m2 IV day 1; Oxaliplatin 85 mg/m2 IV day 1; Leucovorin 400 mg/m2 IV day 1; 5-fluorouracil 2,400 mg/m2 IV days 1-3 (no bolus); Pegfilgrastim 6 mg SC on-body injector day 3 (optional, up to investigator's discretion, can alternatively do day 4 without on-body injector); Suggested supportive care medications: fosaprepitant 150 mg IV day 1, dexamethasone 12 mg IV day 1, ondansetron 16 mg IV day 1, dexamethasone 4 mg PO q AM days 2-3, ondansetron 8 mg PO BID days 2-3.; Radiation: Proton beam radiation; Proton beam radiation will consist of 5 daily doses of 5 GyE total, ideally administered Monday through Friday but can be administered within 7 business days, between cycles 6 and 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended phase II dose and schedule (RP2D) of short-course PRT integrated within adjuvant mFOLFIRINOX	Using a 3+3 dose-escalation schema, 2-12 patients will be required to determine the RP2D.	6 months
Safety (adverse events) of short-course PRT integrated within adjuvant mFOLFIRINOX	adverse event data will be collected and presented as descriptive statistics using the CTCAE version 5.0	6 months
Feasibility (rate of successful completion) of short-course PRT integrated within adjuvant mFOLFIRINOX	we will track the success rate in screening patients, completion of proton beam planning, completion of proton beam treatment, and completion of adjuvant therapy (including number of cycles completed and relative dose intensity).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival (RFS)	Defined as time from surgery until evidence of disease recurrence.	6 months
Overall survival (OS)	Defined as time from surgery until death from any cause or last follow-up.	6 months

Collaborators and Investigators

• Sponsor: Georgetown University
• Investigators: Principal Investigator: Benjamin Weinberg, MD, Georgetown University

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: March 19, 2019
• First Submitted That Met QC Criteria: March 20, 2019
• First Posted (Actual): March 21, 2019

Study Record Updates

• Last Update Posted (Actual): July 29, 2021
• Last Update Submitted That Met QC Criteria: July 27, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Pancreas; Radiation; mFOLFIRINOX
• Other Study ID Numbers: 2018-1021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes