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Neoadjuvant Accelerated Short Course Radiation Therapy With Proton Beam and Capecitabine for Resectable Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT00438256
Recruitment Status : Completed
First Posted : February 22, 2007
Results First Posted : January 23, 2019
Last Update Posted : January 23, 2019
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Theodore Sunki Hong, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pancreatic Cancer
Interventions Procedure: Proton Beam Radiation
Drug: Capecitabine
Enrollment 50
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Proton Beam Radiation/ Capecitabine Dose Level 1 Proton Beam Radiation/ Capecitabine Dose Level 2 Proton Beam Radiation/ Capecitabine Dose Level 3 Proton Beam Radiation/ Capecitabine Dose Level 4
Hide Arm/Group Description

Procedure/Surgery:

Proton Beam Radiation: Given over 10 Radiation Sessions over 2 weeks

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Procedure/Surgery:

Proton Beam Radiation: Given over 5 Radiation sessions: 3 in week 1 and 2 in week 2

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Procedure/Surgery:

Proton Beam Radiation: Given over 5 Radiation sessions: 4 in week 1 and 1 in week 2

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Procedure/Surgery:

Proton Beam Radiation: Given over 5 Radiation Sessions in one week

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Period Title: Overall Study
Started 3 3 3 41
Surgical Resection 1 2 2 34
Completed 1 2 2 32
Not Completed 2 1 1 9
Reason Not Completed
Ineligible for Resection             2             1             1             7
Excluded final Diagnosis             0             0             0             2
Arm/Group Title Proton Beam Radiation/ Capecitabine
Hide Arm/Group Description

Procedure/Surgery:

Proton Beam Radiation: Given over different schedules and duration

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Overall Number of Baseline Participants 50
Hide Baseline Analysis Population Description
Phase 1 radiation schedule escalation arms were combined with the phase II dose arm to highlight overall trends of the regimen
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 50 participants
65
(49 to 92)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Female
23
  46.0%
Male
27
  54.0%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 50 participants
50
 100.0%
CA19-9 level at baseline   [1] 
Median (Full Range)
Unit of measure:  Units per milliliter
Number Analyzed 50 participants
136.5
(1 to 15151)
[1]
Measure Description: Carbohydrate antigen (CA) 19-9 is an antigen released by pancreatic cancer cells.
Tumor size on CT  
Median (Full Range)
Unit of measure:  Centimeters
Number Analyzed 50 participants
2.9
(1.1 to 4.3)
1.Primary Outcome
Title Number of Participants With Dose Limiting Toxicities in the 5 Radiation Sessions in One Week Arm
Hide Description

The number of participants that experienced a dose limiting toxicity in the arm where radiation was administered over 5 consecutive for a total dose of 25 Gray Equivalents (GyE) (Group 4). Participants were monitored for potential Dose Limiting Toxicities (DLT) for three weeks after the start of radiation. DLTs included:

  1. Any grade 3 non-hematologic or hematologic toxicity requiring a greater than 7 day interruption in therapy (excluding alopecia and nausea/vomiting not controlled by optimal supportive care or
  2. Any grade 4 non-hematologic toxicity or
  3. Any grade 4 neutropenia or thrombocytopenia as defined by Common Terminology Criteria for Adverse Events (CTCAE v3.0)
Time Frame 3 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The participants treated with radiation therapy at the 5 fractions over 5 consecutive days
Arm/Group Title Proton Beam Radiation/ Capecitabine
Hide Arm/Group Description:

Procedure/Surgery:

Proton Beam Radiation: 5 fractions over 5 consecutive days for a total of 25 Gray Equivalents (GyE)

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Overall Number of Participants Analyzed 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2.Primary Outcome
Title Number of Participants With Grade 3 or Greater Toxicity in Phase II
Hide Description Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 3). The regimen was considered to be tolerated if less than 20% of participants experienced a grade 3 or greater toxicity.
Time Frame 30 days after the end of treatment, up to approximately 6 months total
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Phase II portion of the trial
Arm/Group Title Phase II: Proton Beam Radiation/ Capecitabine
Hide Arm/Group Description:

Procedure/Surgery:

Proton Beam Radiation: 5 fractions over 5 consecutive days for a total of 25 Gray Equivalents (GyE)

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Overall Number of Participants Analyzed 35
Measure Type: Count of Participants
Unit of Measure: Participants
2
   5.7%
3.Secondary Outcome
Title Number of Participants With a Pathological Complete Response
Hide Description All patients that received surgery underwent a full pathological review of their pancreaticoduodenectomy specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th. Initial gross evaluation and identification of resection margins was performed jointly by the surgeon and the pathologist. Pathological complete response will be defined as the absence of any viable tumor cells within the pathologic specimen.
Time Frame at the time of surgery (28-42 days after start of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The eligible participants who underwent surgical resection. The phase I arms and Phase II group were combined together for analysis.
Arm/Group Title Proton Beam Radiation/ Capecitabine
Hide Arm/Group Description:

Procedure/Surgery:

Proton Beam Radiation: Given over different schedules and duration

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
4.Secondary Outcome
Title Median Progression Free Survival
Hide Description

The median amount of time from the start of treatment until death or disease progression, whichever occurs first.

Progressive Disease (PD): A 20% or greater increase in the sum of Longest Diameter (LD) of all target lesions, taking as reference the smallest sum LD recorded since baseline.

Time Frame from the start of treatment until death or progression, median duration of 10.4 months
Hide Outcome Measure Data
Hide Analysis Population Description
Two participants were excluded from the analysis because of ineligible final diagnoses (cholangiocarcinoma and autoimmune pancreatitis)
Arm/Group Title Proton Beam Radiation/ Capecitabine
Hide Arm/Group Description:

Procedure/Surgery:

Proton Beam Radiation: Given over different schedules and duration

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Overall Number of Participants Analyzed 48
Median (95% Confidence Interval)
Unit of Measure: Months
10.4
(7.5 to 17.1)
5.Secondary Outcome
Title Number of Participants With Surgical Morbidity
Hide Description Number of participants with pancreatic or any other anastomotic leakage within 30 days of surgery
Time Frame 30 days post surgery (surgery was 28-42 days after the start of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The eligible participants who underwent surgical resections. The phase I arms and Phase II group were combined together for analysis.
Arm/Group Title Proton Beam Radiation/ Capecitabine
Hide Arm/Group Description:

Procedure/Surgery:

Proton Beam Radiation: Given over different schedules and duration

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
6.Secondary Outcome
Title 30-Day Post Operative Mortality
Hide Description The number of participants that died within 30 days of undergoing a pancreaticoduodenectomy.
Time Frame 30 days after the time of surgery (Surgery is 28-42 days after start of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
The eligible participants who underwent surgical resection. The phase I arms and Phase II group were combined together for analysis.
Arm/Group Title Proton Beam Radiation/ Capecitabine
Hide Arm/Group Description:

Procedure/Surgery:

Proton Beam Radiation: Given over different schedules and duration

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Overall Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
7.Secondary Outcome
Title Number of Participants With Treatment Related Serious Adverse Events
Hide Description The number of participants that had treatment related serious adverse events. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 3). Adverse events were considered to be serious adverse events if they were grade 3 or greater and were considered to be possibly, probably, or definitely related to treatment.
Time Frame From the start of treatment until 30 days after the end of treatment, up to approximately 5 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Proton Beam Radiation/ Capecitabine Dose Level 1 Proton Beam Radiation/ Capecitabine Dose Level 2 Proton Beam Radiation/ Capecitabine Dose Level 3 Proton Beam Radiation/ Capecitabine Dose Level 4
Hide Arm/Group Description:

Procedure/Surgery:

Proton Beam Radiation: Given over 10 Radiation Sessions over 2 weeks

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Procedure/Surgery:

Proton Beam Radiation: Given over 5 Radiation sessions: 3 in week 1 and 2 in week 2

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Procedure/Surgery:

Proton Beam Radiation: Given over 5 Radiation sessions: 4 in week 1 and 1 in week 2

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Procedure/Surgery:

Proton Beam Radiation: Given over 5 Radiation Sessions in one week

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Overall Number of Participants Analyzed 3 3 3 41
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
2
   4.9%
Time Frame From the start of treatment until 30 days after the end of treatment, up to approximately approximately 5 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Proton Beam Radiation/ Capecitabine Dose Level 1 Proton Beam Radiation/ Capecitabine Dose Level 2 Proton Beam Radiation/ Capecitabine Dose Level 3 Proton Beam Radiation/ Capecitabine Dose Level 4
Hide Arm/Group Description

Procedure/Surgery:

Proton Beam Radiation: Given over 10 Radiation Sessions over 2 weeks

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Procedure/Surgery:

Proton Beam Radiation: Given over 5 Radiation sessions: 3 in week 1 and 2 in week 2

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Procedure/Surgery:

Proton Beam Radiation: Given over 5 Radiation sessions: 4 in week 1 and 1 in week 2

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

Procedure/Surgery:

Proton Beam Radiation: Given over 5 Radiation Sessions in one week

Drug:

Capecitabine: Given orally starting on day one of radiation therapy for 2 weeks

All-Cause Mortality
Proton Beam Radiation/ Capecitabine Dose Level 1 Proton Beam Radiation/ Capecitabine Dose Level 2 Proton Beam Radiation/ Capecitabine Dose Level 3 Proton Beam Radiation/ Capecitabine Dose Level 4
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/3 (0.00%)      0/3 (0.00%)      0/3 (0.00%)      0/41 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Proton Beam Radiation/ Capecitabine Dose Level 1 Proton Beam Radiation/ Capecitabine Dose Level 2 Proton Beam Radiation/ Capecitabine Dose Level 3 Proton Beam Radiation/ Capecitabine Dose Level 4
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/3 (0.00%)      0/3 (0.00%)      2/41 (4.88%)    
Gastrointestinal disorders         
Colitis  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/41 (2.44%)  1
Musculoskeletal and connective tissue disorders         
Pain - Chest Wall  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 1/41 (2.44%)  1
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Proton Beam Radiation/ Capecitabine Dose Level 1 Proton Beam Radiation/ Capecitabine Dose Level 2 Proton Beam Radiation/ Capecitabine Dose Level 3 Proton Beam Radiation/ Capecitabine Dose Level 4
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      3/3 (100.00%)      3/3 (100.00%)      41/41 (100.00%)    
Gastrointestinal disorders         
Constipation  1  1/3 (33.33%)  1 1/3 (33.33%)  3 1/3 (33.33%)  1 15/41 (36.59%)  23
Diarrhea w/o prior colostomy  1  0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 4/41 (9.76%)  6
Dyspepsia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 2/41 (4.88%)  2
Nausea  1  3/3 (100.00%)  3 3/3 (100.00%)  4 3/3 (100.00%)  5 29/41 (70.73%)  43
Vomiting  1  2/3 (66.67%)  3 1/3 (33.33%)  1 1/3 (33.33%)  2 7/41 (17.07%)  8
General disorders         
Fatigue  1  3/3 (100.00%)  6 2/3 (66.67%)  4 3/3 (100.00%)  5 21/41 (51.22%)  33
Fever w/o neutropenia  1  0/3 (0.00%)  0 1/3 (33.33%)  1 0/3 (0.00%)  0 3/41 (7.32%)  3
Investigations         
ALT- SGPT  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 4/41 (9.76%)  4
AST- SGOT  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/41 (7.32%)  3
Bilirubin  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 2/41 (4.88%)  2
Weight loss  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 3/41 (7.32%)  3
Metabolism and nutrition disorders         
Anorexia  1  1/3 (33.33%)  3 2/3 (66.67%)  4 2/3 (66.67%)  4 7/41 (17.07%)  10
Dehydration  1  1/3 (33.33%)  1 0/3 (0.00%)  0 0/3 (0.00%)  0 2/41 (4.88%)  2
Hyperglycemia  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 10/41 (24.39%)  20
Musculoskeletal and connective tissue disorders         
Abdomen- pain  1  2/3 (66.67%)  3 1/3 (33.33%)  4 1/3 (33.33%)  4 9/41 (21.95%)  12
Back- pain  1  0/3 (0.00%)  0 1/3 (33.33%)  1 1/3 (33.33%)  1 3/41 (7.32%)  3
Extremity-limb- pain  1  0/3 (0.00%)  0 0/3 (0.00%)  0 1/3 (33.33%)  1 2/41 (4.88%)  3
Psychiatric disorders         
Anxiety  1  0/3 (0.00%)  0 0/3 (0.00%)  0 0/3 (0.00%)  0 4/41 (9.76%)  7
1
Term from vocabulary, CTCAE (3.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Theodore Hong, MD
Organization: Massachusetts General Hospital
Phone: 617-724-1159
EMail: TSHONG1@mgh.harvard.edu
Layout table for additonal information
Responsible Party: Theodore Sunki Hong, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00438256     History of Changes
Other Study ID Numbers: 06-248
First Submitted: February 20, 2007
First Posted: February 22, 2007
Results First Submitted: October 11, 2018
Results First Posted: January 23, 2019
Last Update Posted: January 23, 2019