Study of Proton Therapy in Adjuvant Pancreatic Cancer

NCT ID: NCT03885284

Last Updated: 2024-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-15
• Study Completion Date: 2023-11-08

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

Conditions

Resected Pancreatic Adenocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Level 1

mFOLFIRINOX + Proton beam radiation

Radiation given on days 8-12 of cycle 6

Group Type: EXPERIMENTAL

mFOLFIRINOX

Intervention Type: DRUG

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.

Proton beam radiation

Intervention Type: 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

Dose Level 2

mFOLFIRINOX + Proton beam radiation

Radiation given on days 15-19 of cycle 6

Group Type: EXPERIMENTAL

mFOLFIRINOX

Intervention Type: DRUG

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.

Proton beam radiation

Intervention Type: 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

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Georgetown University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benjamin Weinberg, MD

Role: PRINCIPAL_INVESTIGATOR

Georgetown University

Locations

Georgetown University Medical Center - Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018-1021

Identifier Type: -

Identifier Source: org_study_id