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Carbon Ion Radiation Therapy for Locally Advanced Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT03403049
Recruitment Status : Recruiting
First Posted : January 18, 2018
Last Update Posted : January 18, 2018
Sponsor:
Collaborator:
Shanghai Proton and Heavy Ion Center
Information provided by (Responsible Party):
Nitin Ohri, Albert Einstein College of Medicine, Inc.

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.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Cancer Radiation: Carbon Ion Drug: Gemcitabine + Cisplatin Drug: Gemcitabine + Capecitabine Drug: Gemcitabine + Erlotinib Drug: Gemcitabine Radiation: Photon Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Phase I Clinical Trial of Carbon Ion Radiation Therapy for Locally Advanced, Unresectable Pancreatic Cancer
Study Start Date : April 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1
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
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.

Drug: Gemcitabine + Cisplatin

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.


Drug: Gemcitabine + Capecitabine

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.


Drug: Gemcitabine + Erlotinib

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.


Drug: Gemcitabine

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.


Radiation: Photon
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.




Primary Outcome Measures :
  1. Dose-limiting toxicity [ Time Frame: 90 days ]
    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.


Secondary Outcome Measures :
  1. Any grade 2 or higher treatment-related toxicity, scored using CTCAE v. 4.0 [ Time Frame: through study completion, an average of 1 year ]
    Any grade 2 or higher treatment-related toxicity, scored using CTCAE v. 4.0

  2. Radiographic changes following completion of study therapy (RECIST v. 1.1) [ Time Frame: through study completion, an average of 1 year ]
    Radiographic changes following completion of study therapy (RECIST v. 1.1)

  3. Overall survival duration [ Time Frame: through study completion, an average of 1 year ]
    The length of time from study inclusion until death from any cause

  4. Progression-free survival duration [ Time Frame: through study completion, an average of 1 year ]
    The length of time from study inclusion until death from any cause or disease progression at any site

  5. Quality of life [ Time Frame: through study completion, an average of 1 year ]
    Quality of life will be assessed at various time points using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30)



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed the informed consent form;
  2. Age ≥ 18;
  3. Capable of following the protocol
  4. Cytologically or histologically proven diagnosis of adenocarcinoma of the pancreas;
  5. 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;
  6. No evidence of distant metastases based on imaging evaluation;
  7. Maximum tumor and positive lymph node diameter ≤ 6 cm;
  8. ECOG Performance Status 0-1;
  9. Life expectancy ≥ 12 weeks;
  10. 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);
  11. Adequate liver function: total bilirubin <1.5 x ULN, and AST and ALT <2.5 x ULN;
  12. 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;
  13. 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.
  14. Prior receipt of 2-4 cycles of Gemcitabine-based systemic chemotherapy.

Exclusion Criteria:

  1. Lack of pathologic confirmation of pancreatic malignancy prior to treatment initiation;
  2. ECOG Performance Status >=2;
  3. Poor liver, kidney and bone marrow function that do not meet the requirements for treatment;
  4. Persistent grade ≥ 2 toxicity due to previous cancer treatment;
  5. Patient has previously received abdominal radiation therapy or abdominal radioactive seed implantation;
  6. 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;
  7. 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.;
  8. If the doctor determines that the heavy proton or carbon ion dosage radiotherapy will not bring any benefit to the patient;
  9. Patients suffering from another illness or other factors that could affect the proton or carbon ion therapy;
  10. Pregnant (verified by serum or urine β-HCG test) or breastfeeding females;
  11. Drug-abuse or alcohol dependency;
  12. 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;
  13. HBV positive patients suffering from replicative stage of hepatitis virus, requiring antiretroviral therapy but cannot due to a concomitant disease;
  14. Patients with a history of mental illness that may prevent their completion of treatment;
  15. Patients with serious complications that could affect the course of treatment, including:

    • Unstable angina, congestive heart failure, or myocardial infarction requiring hospital admittance over the last 6 months;
    • Acute or systemic bacterial infection;
    • Chronic exacerbated obstructive pulmonary disease or other respiratory system disease requiring inpatient treatment;
    • Impaired liver function or impaired kidney function;
    • Patients suffering from immunosuppression;
  16. Patients with contraindications to receiving radiotherapy, such as a serious connective tissue disease (eg: scleroderma)
  17. Patients that are unable to understand the objective of the treatment/cannot sign the informed consent form;
  18. Patients that lack civil capacity to act or whose civil capacity to act is limited.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03403049


Contacts
Contact: Guo-Liang Jiang, MD +86-021-38296666-53609 guoliang.jiang@sphic.org.cn
Contact: Chandan Guha, M.B.B.S., Ph.D. (718) 920-2702 CGuha@montefiore.org

Locations
United States, New York
Albert Einstein College of Medicine Not yet recruiting
Bronx, New York, United States, 10461
Contact: Ravindran S. Kathirithamby, MBA    718-430-3697    ravindran.kathirithamby@einstein.yu.edu   
China, Shanghai
Shanghai Proton and Heavy Ion Center Recruiting
Shanghai, Shanghai, China
Contact: Guo-Liang Jiang, M.D.    +86-021-38296666-53609    guoliang.jiang@sphic.org.cn   
Sponsors and Collaborators
Albert Einstein College of Medicine, Inc.
Shanghai Proton and Heavy Ion Center
Investigators
Principal Investigator: Chandan Guha, M.B.B.S., Ph.D. Albert Einstein College of Medicine, Inc.

Responsible Party: Nitin Ohri, Associate Professor, Albert Einstein College of Medicine, Inc.
ClinicalTrials.gov Identifier: NCT03403049     History of Changes
Other Study ID Numbers: 2015-5026
261201500022C-0-0-1 ( U.S. NIH Grant/Contract )
First Posted: January 18, 2018    Key Record Dates
Last Update Posted: January 18, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Nitin Ohri, Albert Einstein College of Medicine, Inc.:
pancreatic cancer
pancreas
cancer
locally advanced
unresectable
radiation
radiation therapy
radiotherapy
carbon
carbon ion
ion

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs