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Proton Therapy and Combination Chemotherapy for the Treatment of Resectable Pancreatic Cancer, PROTON-PANC Study

Trial Status: Active

This phase I trial studies the side effects and best dose of short-course proton radiation therapy when given together with chemotherapy in treatment patients with pancreatic cancer that can be removed by surgery (resectable). Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as leucovorin, oxaliplatin, irinotecan, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving proton therapy and chemotherapy may work better than chemotherapy alone in treating patients with pancreatic cancer.

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 margins (R1)
  • Adequate healing post-operatively
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelets >= 100 x 10^9/L
  • Hemoglobin >= 9.0 g/dL. Patients may have a transfusion of red blood cells to meet the hemoglobin requirement
  • Serum creatinine =< 1.5 x upper normal limit of institution’s normal range or creatinine clearance >= 30 mL/min for subjects with creatinine levels above institutional normal
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x the upper normal limit of institution’s normal range
  • Total bilirubin =< 1.5 x the upper normal limit of institution’s normal range
  • Partial thromboplastin time (PTT) must be =< 1.5 x upper normal limit of institution’s normal range
  • 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 allowed
  • 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 amenorrhoeic 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 hepatitis B surface antigen (HBsAg) testing is negative * Patients with resolved hepatitis C infection are eligible if viral ribonucleic acid (RNA) polymerase chain reaction (PCR) is negative
  • Uncontrolled human immunodeficiency virus (HIV) infection (CD4 count must be at least 200 and viral load undetectable on a stable antiretroviral regimen to be eligible for enrollment)
  • Major surgery within 4 weeks prior to enrollment

District of Columbia

Washington
MedStar Georgetown University Hospital
Status: ACTIVE
Contact: Benjamin Adam Weinberg
Phone: 202-444-2223

PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose and schedule (RP2D) of short-course proton radiation therapy (PRT) integrated within adjuvant leucovorin, fluorouracil, irinotecan, and oxaliplatin (FFX) (radiation 12 days following chemotherapy or 5 days following chemotherapy) for resected pancreatic ductal adenocarcinoma (PDAC).

II. To demonstrate the safety and feasibility of short short-course proton radiation within systemic adjuvant chemotherapy with FFX, including the number of cycles received and relative chemotherapy dose-intensity.

EXPLORATORY OBJECTIVES:

I. To determine, in patients with resected PDAC undergoing PRT integrated within adjuvant FFX:

Ia. Median recurrence-free survival (mPFS).

Ib. Median overall survival (mOS).

OUTLINE: This is a dose-escalation study of PRT.

DOSE LEVEL I: Patients receive leucovorin intravenously (IV) over 60 minutes, oxaliplatin IV over 120 minutes, irinotecan IV over 90 minutes, and fluorouracil IV over 46 hours continuously on day 1. Patients may receive pegfilgrastim subcutaneously (SC) on day 3. Cycles repeat every 14 days (cycle 6 only is 28 days) in the absence of disease progression or unacceptable toxicity. Patients also undergo PRT daily for 5 days on days 15-19 of cycle 6 (excluding weekend days).

DOSE LEVEL II: Patients receive leucovorin, oxaliplatin, irinotecan, fluorouracil, and pegfilgrastim as in Dose Level I. Cycles repeat every 21 days (cycle 6 only is 28 days) in the absence of disease progression or unacceptable toxicity. Patients also undergo PRT daily for 5 days on days 8-12 of cycle 6 (excluding weekend days).

After completion of study treatment, patients are followed up every 3 months for up to 24 months.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
MedStar Georgetown University Hospital

Principal Investigator
Benjamin Adam Weinberg

  • Primary ID 2018-1021
  • Secondary IDs NCI-2019-07691
  • Clinicaltrials.gov ID NCT03885284