Carbon Ion Radiation Therapy for Locally Advanced Pancreatic Cancer

NCT03403049 | Completed Phase 1 DMC

• 2 other identifiers: 2015-5026261201500022C-0-0-1
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 2

Brief Summary

This is a phase I trial to determine the maximum tolerated dose of carbon ion radiotherapy for the treatment of locally advanced, unresectable, pancreatic cancer.

Conditions

Pancreatic Cancer; Cancer

Keywords

pancreatic cancer; pancreas; cancer; locally advanced; unresectable; radiation; radiation therapy; radiotherapy; carbon; carbon ion; ion

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity

  Any CTCAE v. 4.03 non-hematologic adverse event of grade 3 or higher or any hematologic adverse event of grade 4 or higher, occurring within 90 days of the start of radiotherapy and deemed to be related to carbon ion radiotherapy.

  90 days

Secondary Outcomes (5)

• Any grade 2 or higher treatment-related toxicity, scored using CTCAE v. 4.0

  through study completion, an average of 1 year

• Radiographic changes following completion of study therapy (RECIST v. 1.1)

  through study completion, an average of 1 year

• Overall survival duration

  through study completion, an average of 1 year

• Progression-free survival duration

  through study completion, an average of 1 year

• The impact in terms of overall quality of life of radiation therapy as assessed by the QLQ-C30 questionnaire

  through study completion, an average of 1 year

Study Arms (1)

Arm 1

EXPERIMENTAL

Dose-escalation phase I clinical study. In the initial dose levels, 'dose-escalation' refers to an increase in the radiotherapy dose delivered using carbon ion radiotherapy along with a corresponding decrease in the dose delivered using photons.

Radiation: Carbon Ion; Drug: Gemcitabine + Cisplatin; Drug: Gemcitabine + Capecitabine; Drug: Gemcitabine + Erlotinib; Drug: Gemcitabine; Radiation: Photon

Interventions

Carbon Ion RADIATION

Study subjects will receive carbon ion radiotherapy (CIRT), with daily fraction sizes of 3 GyE. The total CIRT dose will increase with each dose level. Subjects in dose level 1 and 2 will receive photon radiotherapy as well.

Arm 1

Gemcitabine + Cisplatin DRUG

Combined chemotherapy regimen before/after radiotherapy: gemcitabine-based chemotherapy regimen. All patients will have received 2-4 cycles of gemcitabine-based chemotherapy prior to study registration, with post-chemotherapy imaging demonstrating locally-advanced disease without evidence of distant metastatic disease spread. Patients who received chemotherapy regimens other than those listed above may be considered for study enrollment at the discretion of the lead investigators, provided that all other eligibility criteria are satisfied. Gemcitabine-based chemotherapy will be continued starting 3-5 weeks after completion of radiotherapy until disease progression, intolerability, or the patient's decline of chemotherapy.

Arm 1

Gemcitabine + Capecitabine DRUG

Combined chemotherapy regimen before/after radiotherapy: gemcitabine-based chemotherapy regimen. All patients will have received 2-4 cycles of gemcitabine-based chemotherapy prior to study registration, with post-chemotherapy imaging demonstrating locally-advanced disease without evidence of distant metastatic disease spread. Patients who received chemotherapy regimens other than those listed above may be considered for study enrollment at the discretion of the lead investigators, provided that all other eligibility criteria are satisfied. Gemcitabine-based chemotherapy will be continued starting 3-5 weeks after completion of radiotherapy until disease progression, intolerability, or the patient's decline of chemotherapy.

Arm 1

Gemcitabine + Erlotinib DRUG

Combined chemotherapy regimen before/after radiotherapy: gemcitabine-based chemotherapy regimen. All patients will have received 2-4 cycles of gemcitabine-based chemotherapy prior to study registration, with post-chemotherapy imaging demonstrating locally-advanced disease without evidence of distant metastatic disease spread. Patients who received chemotherapy regimens other than those listed above may be considered for study enrollment at the discretion of the lead investigators, provided that all other eligibility criteria are satisfied. Gemcitabine-based chemotherapy will be continued starting 3-5 weeks after completion of radiotherapy until disease progression, intolerability, or the patient's decline of chemotherapy.

Arm 1

Gemcitabine DRUG

Combined chemotherapy regimen before/after radiotherapy: gemcitabine-based chemotherapy regimen. All patients will have received 2-4 cycles of gemcitabine-based chemotherapy prior to study registration, with post-chemotherapy imaging demonstrating locally-advanced disease without evidence of distant metastatic disease spread. Patients who received chemotherapy regimens other than those listed above may be considered for study enrollment at the discretion of the lead investigators, provided that all other eligibility criteria are satisfied. Gemcitabine-based chemotherapy will be continued starting 3-5 weeks after completion of radiotherapy until disease progression, intolerability, or the patient's decline of chemotherapy.

Arm 1

Photon RADIATION

During this study, the prescribed dose shall be administered according to the dose escalation shown in the table, starting with dose level 1. The carbon ion dose shall be gradually escalated while gradually reducing the dose of photons until eventually administering a full dose of 56 GyE/14 Fx carbon ions (fractional dose of 4 GyE). Dose escalation will be performed in parallel for two patient groups: patients whose pancreatic tumors are greater than 5 mm from the duodenum (Group A) and those whose tumors are within 5 mm of the duodenum (Group B). Enrolled patients will be monitored for 90 days after radiotherapy starts for any acute toxic reaction and to explore the maximum tolerated dose, in addition to being observed for any related long-term toxic reactions in accordance with the protocol.

Arm 1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed the informed consent form;
• Age ≥ 18;
• Capable of following the protocol
• Cytologically or histologically proven diagnosis of adenocarcinoma of the pancreas;
• Unresectable adenocarcinoma of the pancreas by radiographic criteria according to the criteria of the NCCN Guidelines and based on post-chemotherapy imaging or due to medical contraindications to radical resection;
• No evidence of distant metastases based on imaging evaluation;
• Maximum tumor and positive lymph node diameter ≤ 6 cm;
• ECOG Performance Status 0-1;
• Life expectancy ≥ 12 weeks;
• Adequate blood function: absolute neutrophil count (ANC) ≥1.5 x 109/L, platelet count ≥100 x 109/L, and hemoglobin ≥9 g/dL (use of transfusion to achieve said levels or greater is acceptable);
• Adequate liver function: total bilirubin \<1.5 x ULN, and AST and ALT \<2.5 x ULN;
• Adequate kidney function: serum creatinine ≤1.25 x ULN or calculated creatinine clearance rate ≥50mL/min and urine protein \<2+.If the patient's baseline urine protein is at ≥2+, urine samples must be taken for 24 hours to verify that urine protein is ≤1g;
• Laboratory studies within 14 days prior to registration demonstrating that the internationalization standard ratio (INR) ≤1.5 and prothrombin time (PPT) ≤1.5 x ULN.
• Prior receipt of 2-4 cycles of Gemcitabine-based systemic chemotherapy.

You may not qualify if:

• Lack of pathologic confirmation of pancreatic malignancy prior to treatment initiation;
• ECOG Performance Status \>=2;
• Poor liver, kidney and bone marrow function that do not meet the requirements for treatment;
• Persistent grade ≥ 2 toxicity due to previous cancer treatment;
• Patient has previously received abdominal radiation therapy or abdominal radioactive seed implantation;
• Those wearing a cardiac pacemaker or another type of metal prosthetic implant whose normal functions may suffer interference from high energy radiation or that could affect the radiation target area;
• Where it is not possible to achieve the predetermined safety dose limit with the dose equivalent limit of the organ at risk such as the liver or digestive tract, etc.;
• If the doctor determines that the heavy proton or carbon ion dosage radiotherapy will not bring any benefit to the patient;
• Patients suffering from another illness or other factors that could affect the proton or carbon ion therapy;
• Pregnant (verified by serum or urine β-HCG test) or breastfeeding females;
• Drug-abuse or alcohol dependency;
• HIV positive, including those that have received antiretroviral therapy; replicative stage of chronic Hepatitis B virus; active stage of Hepatitis C; and active stage of syphilis;
• HBV positive patients suffering from replicative stage of hepatitis virus, requiring antiretroviral therapy but cannot due to a concomitant disease;
• Patients with a history of mental illness that may prevent their completion of treatment;
• Patients with serious complications that could affect the course of treatment, including:

Sponsors & Collaborators

• Shanghai Proton and Heavy Ion Center: collaborator
• Montefiore Medical Center: lead

Study Sites (2)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Shanghai Proton and Heavy Ion Center

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms

Interventions

Gemcitabine; Cisplatin; Capecitabine; Erlotinib Hydrochloride; Photons

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Elementary Particles; Physical Phenomena; Light; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Optical Phenomena; Radiation; Radiation, Nonionizing

Study Officials

• Chandan Guha, M.B.B.S., Ph.D.

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: January 18, 2018
• Study Start: April 1, 2016
• Primary Completion: July 9, 2019
• Study Completion: July 9, 2019
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1); CN (1)