Trial of Carbon Ion Versus Photon Radiotherapy for Locally Advanced, Unresectable Pancreatic Cancer

NCT03536182 | Withdrawn Phase 3 DMC FDA Device

• 1 other identifier: STU 022016-002
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 2

Brief Summary

To determine if carbon ion radiotherapy improves overall survival versus photon therapy in patients with locally advanced, unresectable pancreatic cancer

Conditions

Locally Advanced Pancreatic Adenocarcinoma

Keywords

Pancreas; Adenocarcinoma.

Outcome Measures

Primary Outcomes (1)

• Over all Survival

  To compare the efficacy of carbon ion-based chemoradiotherapy with x-ray-based chemoradiotherapy for the treatment of locally advanced pancreatic adenocarcinoma by comparison of overall survival following treatment.

  2 Years

Secondary Outcomes (4)

• Progression-free survival

  2 Years

• Patterns-of-failure

  2 years

• Quality-of-life Comparison

  12 Months

• Toxicity using CTCAE 5.0

  2 years

Study Arms (2)

Arm A: Carbon ion radiotherapy

ACTIVE COMPARATOR

The dose calculation algorithms used in Japan and Europe (local effect model, LEM) are different, so the total dose must be modified to ensure consistency 1. Japan : 55.2 GyE in 4.6 GyE per fraction in 12 fractions delivered 4 days a week. At least 90% of each CTV receives at least 95% of the prescribed dose, and 100% of the GTV V95 must receive at least 95% of the prescribed dose. 2. European: . Patients treated in Europe should receive 57.6 GyE in 4.8 GyE per fraction in 12 fractions delivered 4 days a week. At least 90% of CTV receives at least 95% of the prescribed dose, and 100% of the GTV V95 must receive at least 95% of the prescribed dose. This evaluation will occur in the LEM system

Radiation: Carbon Ion Radiation Therapy (CIRT)

Arm B: Photon radiotherapy

ACTIVE COMPARATOR

50.4-56 Gy in 1.8-2.0 Gy per fraction in 28 fractions delivered 5 days a week. The plan should be normalized such that 100% of the PTV receives at least 48.9 Gy (i.e. 97% of 50.4 Gy). In addition, 100% of the GTV should receive at least 50.4 Gy. The maximum dose allowed to a point volume (0.03 mL) is 115% of the prescribed dose.

Radiation: Intensity Modulated Radiation Therapy (IMRT)

Interventions

Carbon Ion Radiation Therapy (CIRT) RADIATION

Patient will receive CIRT daily, 4 days a week for a total of 12 fractions/treatments plus concurrent chemotherapy (gemcitabine) weekly for 3 weeks. Gemcitabine will be given intravenously over about 1 hour in the outpatient clinic. Within 6 weeks of completing radiotherapy, patient will start 4 cycles of chemotherapy. If the doctor chooses gemcitabine+nab-Paclitaxel, patient will receive gemcitabine and nab-paclitaxel intravenously once a week for 3 weeks then 1 week off, for a total of 4 cycles (16 weeks). If the doctor chooses FOLFIRINOX, then patient will receive oxaliplatin, irinotecan, infusional 5-fluorouracil, and possibly leucovorin, all intravenously, every 2 weeks, for a total of 16 weeks.

Arm A: Carbon ion radiotherapy

Intensity Modulated Radiation Therapy (IMRT) RADIATION

Patient will receive IMRT daily, 5 days a week for a total of 28 fractions/treatments plus concurrent chemotherapy (gemcitabine or capecitabine) weekly for 5 weeks. Gemcitabine will be given intravenously over about 1 hour in the outpatient clinic,within 6 weeks of completing radiotherapy,patient will start 4 cycles of chemotherapy. If the doctor chooses gemcitabine+nab-Paclitaxel, patient will receive gemcitabine and nab-paclitaxel intravenously once a week for 3 weeks then 1 week off, for a total of 4 cycles (16 weeks). If the doctor chooses FOLFIRINOX, then patient will receive oxaliplatin, irinotecan, infusional 5-fluorouracil, and possibly leucovorin, all intravenously, every 2 weeks, for a total of 16 weeks.

Arm B: Photon radiotherapy

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must be willing and capable to provide informed consent within the 30 days prior to registration to participate in the protocol.
• Histological and/or cytological diagnosis of pancreas adenocarcinoma must be done at any point prior to registration
• Unresectable by radiographic or exploration within 30 days of registration
• Age ≥ 18 years.
• Distance from the pancreas tumor edge to the bowel and stomach \> 3 mm (in both the prone and supine positions)
• Tumor does not exceed 15 cm in greatest dimension
• No evidence for metastatic disease as assessed by CT imaging of the chest, abdomen and pelvis OR by PET-CT within the 30 days prior to registration. Pancreas-protocol CT or magnetic resonance imaging (MRI) with gadolinium (for patients who cannot receive CT contrast) is required as part of this evaluation.
• Zubrod performance status of 0-1, within 30 days prior to registration.
• Adequate hematologic, renal, and liver function as defined by:Adequate hematologic, renal, and liver function as defined by:
• Absolute neutrophil count \> 1500 cells/mm3 Creatinine \<1.5 mg/dL Hemoglobin ≥ 8.0 g/dL AST and ALT \< 2.5 X ULN Bilirubin ≤ 1.5 times the ULN (after stent placement, if necessary)
• Patients must complete all required pretreatment evaluations
• Able to travel to a foreign country within approximately 4 weeks of randomization (for patients enrolled outside of Japan and Italy)
• If a patient receives 1 or 2 cycles of chemotherapy at an outside facility, pre-treatment laboratory values must meet the above criteria. If the protocol-compliant imaging had not been obtained prior to chemotherapy, they may be performed prior to registration and any additional chemotherapy being infused.
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

You may not qualify if:

• Subjects receiving other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or nab-paclitaxel or other agents used in study.
• Subjects who are pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Prior radiation to the upper abdomen
• Placement of a metal stent for relief of biliary obstruction (metal stents may be placed following completion of radiation therapy).
• Body weight \>100 kg
• Active inflammatory bowel disease or active gastric/duodenal ulcer
• Metal implants in the upper abdomen
• Expected medical intolerance of radiotherapy, concurrent chemotherapy, and/or adjuvant chemotherapy.
• History of HIV or hepatitis B or C

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (2)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

National Institute of Radiological Sciences,4-9-1, Anagawa, Inage-ku,

Chiba, 263-8555, Japan

Location

MeSH Terms

Conditions

Adenocarcinoma

Interventions

Heavy Ion Radiotherapy; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted

Study Officials

• David Sher, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Eligible patients will be randomized in a 2:1 fashion (carbon:photon) between carbon ion radiotherapy or intensity modulated radiation therapy. Assuming a 10% dropout risk, the study will have 82% power to detect an increase in 2-year survival from 22% to 48% with carbon ion radiotherapy.

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: May 24, 2018
• Study Start: May 29, 2019
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2023
• Last Updated: May 26, 2021

Record last verified: 2021-05

Locations

US (1); JP (1)