Short Course Radiation Therapy With Proton Or Photon Beam Capecitabine And Hydroxychloroquine For Resectable Pancreatic Cancer

Study Overview

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

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.

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).

Pancreatic Cancer

DRUG: Capecitabine
DRUG: Hydroxychloroquine
RADIATION: Proton or Photon Radiation Therapy

11-073

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-07-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2021-02-01
First Submitted that Met QC Criteria 2011-12-14	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2021-02-02
First Posted (ACTUAL) 2011-12-16	Results First Posted N/A	Last Verified 2021-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Hydroxychloroquine Hydroxychloroquine with chemoradiation	DRUG: Capecitabine 825 mg/m2 BID orally for a total of 10 days (M-F of weeks 2 and 3) DRUG: Hydroxychloroquine 400 mg BID from study day 1 until surgery. Dosing resumed upon discharge from hospital RADIATION: Proton or Photon Radiation Therapy Daily, beginning Week 2 for 5 consecutive days

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Hydroxychloroquine

Hydroxychloroquine with chemoradiation

DRUG: Capecitabine

825 mg/m2 BID orally for a total of 10 days (M-F of weeks 2 and 3)

DRUG: Hydroxychloroquine

400 mg BID from study day 1 until surgery. Dosing resumed upon discharge from hospital

RADIATION: Proton or Photon Radiation Therapy

Daily, beginning Week 2 for 5 consecutive days

Primary Outcome Measures	Measure Description	Time Frame
Progression-free survival	To determine the progression-free survival of the addition of hydroxychloroquine to preoperative short course, chemoradiation therapy and adjuvant gemcitabine chemotherapy	2 years

Secondary Outcome Measures	Measure Description	Time Frame
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	2 years
Overall survival	To determine overall survival in patients treated with preoperative capecitabine + hydroxychloroquine and short course radiation therapy	2 years
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	2 years
Surgical morbidity	To determine the surgical morbidity in patients undergoing pancreaticoduodenectomy who received preoperative capecitabine + hydroxychloroquine and external beam radiation therapy	2 years
Post-operative Mortality	To determine 30-day post-operative mortality after pancreaticoduodenectomy in patients who receive preoperative capecitabine and external beam radiation therapy	2 weeks
Biomarkers	To explore biomarkers of autophagy with hydroxychloroquine therapy and explore correlation with progression-free survival	2 years
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)	2 years
Local control	To determine local tumor control at 2 years post treatment in study participants	2 years
Describe QoL	To describe quality of life, symptom burden and mood in the study population	2 Years
Measure utilization of health services	Measure utilization of health services (ER, hospital and ICU visits) in the study population	2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Theodore S Hong, MD, Massachusetts General Hospital

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record