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Short Course Radiation Therapy With Proton or Photon Beam Capecitabine and Hydroxychloroquine for Resectable Pancreatic Cancer

Primary Purpose

Pancreatic Cancer

Status
Unknown status
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Hydroxychloroquine
Proton or Photon Radiation Therapy
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring resectable pancreatic cancer, pancreaticoduodenectomy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Cytologic or histologic proof of pancreatic ductal carcinoma
  • Life expectancy > 3 months
  • Adequate organ and marrow function

Exclusion Criteria:

  • Evidence of metastatic disease
  • Pregnant or breast-feeding
  • Tumors in the body or tail of the pancreas
  • Serious concomitant systemic disorders such as significant cardiac or pulmonary morbidity (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, ongoing infection as manifest by fever
  • Prior chemotherapy or radiation for treatment of the patient's pancreatic tumor
  • Diagnosis of other invasive carcinomas (except basal cell carcinomas/squamous cell carcinoma of the skin) with the last 5 years. Carcinoma in-situ is allowed.
  • Other serious uncontrolled medical conditions
  • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
  • Known, existing uncontrolled coagulopathy
  • Prior systemic fluoropyrimidine therapy (unless given in an adjuvant setting and completed at least 6 months earlier). Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known DPD deficiency
  • Participation in any investigational drug study within 4 weeks preceding the start of study treatment
  • History of uncontrolled seizures, central nervous system disorders, or psychiatric disability
  • Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery
  • Currently taking cimetidine
  • Receiving any other study agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine and HCQ
  • Already taking HCQ or chloroquine for other diagnosis
  • History of Grade 3 or greater retinopathy or keratitis

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hydroxychloroquine

Arm Description

Hydroxychloroquine with chemoradiation

Outcomes

Primary Outcome Measures

Progression-free survival
To determine the progression-free survival of the addition of hydroxychloroquine to preoperative short course, chemoradiation therapy and adjuvant gemcitabine chemotherapy

Secondary Outcome Measures

Pathologic response rate
To determine the complete pathologic response rate of preoperative capecitabine combined with hydroxychloroquine and short course radiation therapy in patients undergoing pancreaticoduodenectomy
Overall survival
To determine overall survival in patients treated with preoperative capecitabine + hydroxychloroquine and short course radiation therapy
Toxicity/Adverse events
To determine the toxicity of capecitabine + hydroxychloroquine and short course radiation therapy in patients with pancreatic cancer via analysis of frequency and grades of reported toxicities and adverse events, such as GI and hematologic toxicities, occurring in study participants
Surgical morbidity
To determine the surgical morbidity in patients undergoing pancreaticoduodenectomy who received preoperative capecitabine + hydroxychloroquine and external beam radiation therapy
Post-operative Mortality
To determine 30-day post-operative mortality after pancreaticoduodenectomy in patients who receive preoperative capecitabine and external beam radiation therapy
Biomarkers
To explore biomarkers of autophagy with hydroxychloroquine therapy and explore correlation with progression-free survival
Pathologic down-staging
To determine pathologic down-staging of hydroxychloroquine-based short course chemoradiation compared to a previous cohort (treated in prior study of neoadjuvant capecitabine + proton therapy)
Local control
To determine local tumor control at 2 years post treatment in study participants
Describe QoL
To describe quality of life, symptom burden and mood in the study population
Measure utilization of health services
Measure utilization of health services (ER, hospital and ICU visits) in the study population

Full Information

First Posted
July 29, 2011
Last Updated
February 1, 2021
Sponsor
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01494155
Brief Title
Short Course Radiation Therapy With Proton or Photon Beam Capecitabine and Hydroxychloroquine for Resectable Pancreatic Cancer
Official Title
Phase II Study of Neoadjuvant Accelerated Short Course Radiation Therapy With Proton or Photon RT Plus Capecitabine and Hydroxychloroquine for Resectable Pancreatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Unknown status
Study Start Date
December 2011 (undefined)
Primary Completion Date
January 2022 (Anticipated)
Study Completion Date
January 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A standard treatment for patients with pancreatic cancer is standard photon radiation in combination with the chemotherapy drug, capecitabine. In this research study the investigators are using standard photon radiation or a different type of radiation therapy called proton beam radiation and adding hydroxychloroquine to be used in combination with capecitabine. In this research study, the investigators are looking to determine if proton or photon beam radiation in combination with hydroxychloroquine and capecitabine is effective in controlling your cancer growth.
Detailed Description
Subjects will be treated in cycles of 28 days. Hydroxychloroquine will be taken orally, daily until the day before surgery and will resume after surgery until study end. Capecitabine will be taken orally, daily. Proton or photon radiation treatment will start on Week 2 and will be delivered daily (5 days in a row, but not weekends or holidays). Radiation treatment will be give on an outpatient basis at the Francis H. Burr Proton Center or the Clark Center for Radiation Oncology at Massachusetts General Hospital. The following tests will be performed weekly: physical exam, routine blood tests, optional blood tests and an eye exam every 3 months while taking hydroxychloroquine. Subjects will have surgery (any time between Weeks 5 to 9) and after surgery resume taking hydroxychloroquine. Subjects will have a follow up visit every 3 months which will include: physical exam, routine blood tests, eye exam, and tumor assessment by chest and abdominal-pelvic CT scan or MRI (every 6 months for the first 2 years and yearly for years 3-5).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
resectable pancreatic cancer, pancreaticoduodenectomy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hydroxychloroquine
Arm Type
Experimental
Arm Description
Hydroxychloroquine with chemoradiation
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
825 mg/m2 BID orally for a total of 10 days (M-F of weeks 2 and 3)
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Other Intervention Name(s)
Plaquenil
Intervention Description
400 mg BID from study day 1 until surgery. Dosing resumed upon discharge from hospital
Intervention Type
Radiation
Intervention Name(s)
Proton or Photon Radiation Therapy
Intervention Description
Daily, beginning Week 2 for 5 consecutive days
Primary Outcome Measure Information:
Title
Progression-free survival
Description
To determine the progression-free survival of the addition of hydroxychloroquine to preoperative short course, chemoradiation therapy and adjuvant gemcitabine chemotherapy
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Pathologic response rate
Description
To determine the complete pathologic response rate of preoperative capecitabine combined with hydroxychloroquine and short course radiation therapy in patients undergoing pancreaticoduodenectomy
Time Frame
2 years
Title
Overall survival
Description
To determine overall survival in patients treated with preoperative capecitabine + hydroxychloroquine and short course radiation therapy
Time Frame
2 years
Title
Toxicity/Adverse events
Description
To determine the toxicity of capecitabine + hydroxychloroquine and short course radiation therapy in patients with pancreatic cancer via analysis of frequency and grades of reported toxicities and adverse events, such as GI and hematologic toxicities, occurring in study participants
Time Frame
2 years
Title
Surgical morbidity
Description
To determine the surgical morbidity in patients undergoing pancreaticoduodenectomy who received preoperative capecitabine + hydroxychloroquine and external beam radiation therapy
Time Frame
2 years
Title
Post-operative Mortality
Description
To determine 30-day post-operative mortality after pancreaticoduodenectomy in patients who receive preoperative capecitabine and external beam radiation therapy
Time Frame
2 weeks
Title
Biomarkers
Description
To explore biomarkers of autophagy with hydroxychloroquine therapy and explore correlation with progression-free survival
Time Frame
2 years
Title
Pathologic down-staging
Description
To determine pathologic down-staging of hydroxychloroquine-based short course chemoradiation compared to a previous cohort (treated in prior study of neoadjuvant capecitabine + proton therapy)
Time Frame
2 years
Title
Local control
Description
To determine local tumor control at 2 years post treatment in study participants
Time Frame
2 years
Title
Describe QoL
Description
To describe quality of life, symptom burden and mood in the study population
Time Frame
2 Years
Title
Measure utilization of health services
Description
Measure utilization of health services (ER, hospital and ICU visits) in the study population
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Cytologic or histologic proof of pancreatic ductal carcinoma Life expectancy > 3 months Adequate organ and marrow function Exclusion Criteria: Evidence of metastatic disease Pregnant or breast-feeding Tumors in the body or tail of the pancreas Serious concomitant systemic disorders such as significant cardiac or pulmonary morbidity (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, ongoing infection as manifest by fever Prior chemotherapy or radiation for treatment of the patient's pancreatic tumor Diagnosis of other invasive carcinomas (except basal cell carcinomas/squamous cell carcinoma of the skin) with the last 5 years. Carcinoma in-situ is allowed. Other serious uncontrolled medical conditions Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome Known, existing uncontrolled coagulopathy Prior systemic fluoropyrimidine therapy (unless given in an adjuvant setting and completed at least 6 months earlier). Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known DPD deficiency Participation in any investigational drug study within 4 weeks preceding the start of study treatment History of uncontrolled seizures, central nervous system disorders, or psychiatric disability Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery Currently taking cimetidine Receiving any other study agents History of allergic reactions attributed to compounds of similar chemical or biologic composition to capecitabine and HCQ Already taking HCQ or chloroquine for other diagnosis History of Grade 3 or greater retinopathy or keratitis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Theodore S Hong, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Short Course Radiation Therapy With Proton or Photon Beam Capecitabine and Hydroxychloroquine for Resectable Pancreatic Cancer

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