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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Theodore Sunki Hong, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01494155
First received: July 29, 2011
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Drug: Capecitabine
Drug: Hydroxychloroquine
Radiation: Proton or Photon Radiation Therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine the complete pathologic response rate of preoperative capecitabine combined with hydroxychloroquine and short course radiation therapy in patients undergoing pancreaticoduodenectomy

  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine overall survival in patients treated with preoperative capecitabine + hydroxychloroquine and short course radiation therapy

  • Toxicity/Adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the surgical morbidity in patients undergoing pancreaticoduodenectomy who received preoperative capecitabine + hydroxychloroquine and external beam radiation therapy

  • Post-operative Mortality [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
    To determine 30-day post-operative mortality after pancreaticoduodenectomy in patients who receive preoperative capecitabine and external beam radiation therapy

  • Biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To explore biomarkers of autophagy with hydroxychloroquine therapy and explore correlation with progression-free survival

  • Pathologic down-staging [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine local tumor control at 2 years post treatment in study participants


Estimated Enrollment: 50
Study Start Date: December 2011
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Other Name: Xeloda
Drug: Hydroxychloroquine
400 mg BID from study day 1 until surgery. Dosing resumed upon discharge from hospital
Other Name: Plaquenil
Radiation: Proton or Photon Radiation Therapy
Daily, beginning Week 2 for 5 consecutive days

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01494155

Contacts
Contact: Theodore S Hong, MD 617-724-1159 tshong1@partners.org
Contact: Tarin Grillo 617-724-3661 tgrillo@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Theodore S Hong, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Theodore S Hong, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Theodore Sunki Hong, Radiation Oncologist, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01494155     History of Changes
Other Study ID Numbers: 11-073
Study First Received: July 29, 2011
Last Updated: October 1, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
resectable pancreatic cancer
pancreaticoduodenectomy

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Capecitabine
Hydroxychloroquine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 02, 2014