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

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ClinicalTrials.gov Identifier: NCT03885284
Recruitment Status : Recruiting
First Posted : March 21, 2019
Last Update Posted : September 6, 2019
Sponsor:
Information provided by (Responsible Party):
Georgetown University

Tracking Information
First Submitted Date  ICMJE March 19, 2019
First Posted Date  ICMJE March 21, 2019
Last Update Posted Date September 6, 2019
Actual Study Start Date  ICMJE July 15, 2019
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
  • Recommended phase II dose and schedule (RP2D) of short-course PRT integrated within adjuvant mFOLFIRINOX [ Time Frame: 6 months ]
    Using a 3+3 dose-escalation schema, 2-12 patients will be required to determine the RP2D.
  • Safety (adverse events) of short-course PRT integrated within adjuvant mFOLFIRINOX [ Time Frame: 6 months ]
    adverse event data will be collected and presented as descriptive statistics using the CTCAE version 5.0
  • Feasibility (rate of successful completion) of short-course PRT integrated within adjuvant mFOLFIRINOX [ Time Frame: 6 months ]
    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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2019)
  • Recurrence-free survival (RFS) [ Time Frame: 6 months ]
    Defined as time from surgery until evidence of disease recurrence.
  • Overall survival (OS) [ Time Frame: 6 months ]
    Defined as time from surgery until death from any cause or last follow-up.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Proton Therapy in Adjuvant Pancreatic Cancer
Official Title  ICMJE Phase I Study of Proton Therapy in Adjuvant Pancreatic Cancer (Proton-PANC)
Brief Summary This trial aims to determine a safe schedule of short-course proton beam radiation therapy with adjuvant mFOLFIRINOX for patients with resected pancreatic adenocarcinoma.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Resected Pancreatic Adenocarcinoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Dose Level 1

    mFOLFIRINOX + Proton beam radiation

    Radiation given on days 8-12 of cycle 6

    Interventions:
    • Drug: mFOLFIRINOX
    • Radiation: Proton beam radiation
  • Experimental: Dose Level 2

    mFOLFIRINOX + Proton beam radiation

    Radiation given on days 15-19 of cycle 6

    Interventions:
    • Drug: mFOLFIRINOX
    • Radiation: Proton beam radiation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 20, 2019)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03885284
Other Study ID Numbers  ICMJE 2018-1021
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Georgetown University
Study Sponsor  ICMJE Georgetown University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Benjamin Weinberg, MD Georgetown University
PRS Account Georgetown University
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP