Carbon Ion Radiation Therapy for Locally Advanced Pancreatic Cancer

Phase 1

Completed

• Conditions: Pancreatic Cancer; Cancer
• Interventions: Radiation: Carbon Ion; Drug: Gemcitabine + Cisplatin; Drug: Gemcitabine + Capecitabine; Drug: Gemcitabine + Erlotinib; Drug: Gemcitabine; Radiation: Photon

• Registration Number: NCT03403049
• Lead Sponsor: Albert Einstein College of Medicine

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-08
• Study Start: 2016-04-01
• Study First Submitted QC: 2018-01-10
• Study First Posted: 2018-01-18
• Primary Completion: 2019-07-09
• Study Completion: 2019-07-09
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-21
• Last Update Posted: 2020-04-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1	Gemcitabine + Cisplatin	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.
Arm 1	Gemcitabine + Capecitabine	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.
Arm 1	Gemcitabine + Erlotinib	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.
Arm 1	Photon	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.
Arm 1	Carbon Ion	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.
Arm 1	Gemcitabine	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.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity	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

Name	Time	Method
Any grade 2 or higher treatment-related toxicity, scored using CTCAE v. 4.0	through study completion, an average of 1 year	Any grade 2 or higher treatment-related toxicity, scored using CTCAE v. 4.0
Progression-free survival duration	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
Overall survival duration	through study completion, an average of 1 year	The length of time from study inclusion until death from any cause
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	Quality of life will be assessed at various time points using the European Organisation for Research and Treatment of Cancer 30 items dealing with fatigue, pain, nausea and vomiting, general condition and social, emotional and cognitive functions. It is currently used in many cancer related clinical trials.
Radiographic changes following completion of study therapy (RECIST v. 1.1)	through study completion, an average of 1 year	Radiographic changes following completion of study therapy (RECIST v. 1.1)

Trial Locations

Locations (2)

Shanghai Proton and Heavy Ion Center; 🇨🇳 Shanghai, Shanghai, China

Albert Einstein College of Medicine; 🇺🇸 Bronx, New York, United States