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Carbon Ion or Conventional Photon Radiation Therapy and Chemotherapy in Treating Patients with Locally Advanced, Unresectable Pancreatic Cancer

Trial Status: Active

This phase III trial studies how well carbon ion radiation therapy works compared to conventional photon radiation therapy when giving together with chemotherapy in treating patients with pancreatic cancer that has spread from its original site of growth to nearby tissues or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable). Carbon ion radiation therapy uses charged carbon particles to kill tumor cells and shrink tumors. Conventional photon radiation therapy, such as intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Drugs used in chemotherapy, such as gemcitabine, nab-paclitaxel, capecitabine, fluorouracil, irinotecan, leucovorin and oxaliplatin 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. Given carbon ion radiation therapy with chemotherapy may kill more tumor cells in patients with pancreatic cancer compared to conventional photon radiation therapy and chemotherapy.

Inclusion Criteria

  • 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
  • Distance from the pancreas tumor edge to the bowel and stomach >= 3 mm
  • Tumor does not exceed 15 cm in greatest dimension
  • No evidence for metastatic disease as assessed by computed tomography (CT) imaging of the chest, abdomen and pelvis OR by positron emission tomography (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
  • Absolute neutrophil count >= 1500 cells/mm^3
  • Creatinine < 1.5 mg/dL
  • Hemoglobin >= 8.0 g/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 X upper limit of normal (ULN) (obtained within 14 days prior to registration [may be taken after stent placement])
  • 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: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

Exclusion Criteria

  • 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 human immunodeficiency virus (HIV) or hepatitis B or C

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: David Jonathan Sher
Phone: 214-645-7607

Japan

Chiba
National Institute of Radiological Sciences (NIRS)
Status: ACTIVE
Contact: Shigeru Yamada

PRIMARY OBJECTIVE:

I. 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 at 2 years following treatment.

SECONDARY OBJECTIVES:

I. To compare progression-free survival between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma.

II. To compare patterns-of-failure between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma.

III. To compare quality-of-life and toxicity outcomes between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma.

EXPLORATORY OBJECTIVE:

I. To compare quality-adjusted survival time between x-ray-based and carbon-ion-based chemoradiotherapy.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Within 6 weeks of the conclusion of the last cycle neoadjuvant chemotherapy, patients undergo carbon ion radiation therapy daily 4 days per week for 3 weeks. Patients also receive concurrent gemcitabine intravenously (IV) over 1 hour during weeks 1-3 of radiotherapy. Starting within 6 weeks of completing radiation therapy, patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30 minutes weekly for 3 weeks or FOLFIRINOX. Treatment repeats every 4 weeks for up to 2 (if receiving neoadjuvant chemotherapy) or 4 (if no prior neoadjuvant chemotherapy) cycles in the absence disease progression or unacceptable toxicity. In countries without access to these drugs, gemcitabine alone is acceptable.

ARM B: Within 6 weeks of the conclusion of the last cycle neoadjuvant chemotherapy, patients undergo intensity-modulated radiation therapy 5 days per weeks for 5 weeks. Patients also receive concurrent gemcitabine IV over 1 hour or capecitabine orally (PO) twice daily (BID) during weeks 1-5 of radiotherapy. Starting within 6 weeks of completing radiation therapy, patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30 minutes weekly for 3 weeks or FOLFIRINOX. Treatment repeats every 4 weeks for up to 2 (if receiving neoadjuvant chemotherapy) or 4 (if no prior neoadjuvant chemotherapy) cycles in the absence disease progression or unacceptable toxicity. In countries without access to these drugs, gemcitabine alone is acceptable.

FOLFIRINOX: Patients receive oxaliplatin IV , leucovorin IV, and irinotecan IV on days 1 and 15, and fluorouracil IV over 46 hours on days 1-3 and 15-17.

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

Trial Phase Phase III

Trial Type Treatment

Lead Organization
UT Southwestern / Simmons Cancer Center-Dallas

Principal Investigator
David Jonathan Sher

  • Primary ID SCCC-05216; STU 022016-002
  • Secondary IDs NCI-2019-03055
  • Clinicaltrials.gov ID NCT03536182