Study of Proton Therapy in Adjuvant Pancreatic Cancer

NCT03885284 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2018-1021
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Resected Pancreatic Adenocarcinoma

Keywords

Pancreas; Radiation; mFOLFIRINOX

Outcome Measures

Primary Outcomes (3)

• Incidence of Dose Limiting Toxicites (DLTs)

  Recommended phase II dose and schedule (RP2D) of short-course PRT integrated within adjuvant mFOLFIRINOX will be based on number of Dose limiting toxicities.

  6 months

• Safety (Adverse Events) of Short-course PRT Integrated Within Adjuvant mFOLFIRINOX

  Dose Limiting Toxicities. 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

  Success rate defined as # of patients that completed proton beam planning, proton beam treatment, and completion of adjuvant therapy

  6 months

Secondary Outcomes (2)

• Recurrence-free Survival (RFS)

  12 months

• Overall Survival (OS)

  2 years

Study Arms (2)

Dose Level 1

EXPERIMENTAL

mFOLFIRINOX + Proton beam radiation Radiation given on days 8-12 of cycle 6

Drug: mFOLFIRINOX; Radiation: Proton beam radiation

Dose Level 2

EXPERIMENTAL

mFOLFIRINOX + Proton beam radiation Radiation given on days 15-19 of cycle 6

Drug: mFOLFIRINOX; Radiation: Proton beam radiation

Interventions

mFOLFIRINOX 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.

Dose Level 1; Dose Level 2

Proton beam radiation 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 1; Dose Level 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Georgetown University: lead

Study Sites (1)

Georgetown University Medical Center - Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Interventions

Proton Therapy

Intervention Hierarchy (Ancestors)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Benjamin Weinberg, MD
• Organization: Georgetown University

baw12@gunet.georgetown.edu

202-444-2223

Study Officials

• Benjamin Weinberg, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: March 21, 2019
• Study Start: July 15, 2019
• Primary Completion: May 24, 2022
• Study Completion: November 8, 2023
• Last Updated: October 24, 2024
• Results First Posted: October 24, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)