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

This study is currently recruiting participants.
Verified April 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: April 10, 2014
Last verified: April 2014

July 29, 2011
April 10, 2014
December 2011
July 2015   (final data collection date for primary outcome measure)
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
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, proton-based chemoradiation therapy and adjuvant gemcitabine chemotherapy
Complete list of historical versions of study NCT01494155 on ClinicalTrials.gov Archive Site
  • 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
  • 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 proton beam radiation therapy in patients undergoing pancreaticduodenectomy
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine overall survival in patients treated with preoperative capecitabine + hydroxychloroquine and proton beam radiation therapy
  • Toxicity/Adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the toxicity of capecitabine + hydroxychloroquine and proton beam radiation therapy in patients with pancreatic cancer via analysis of frequency and grades of reported toxicities and adverse events, such as GI and heamtologic toxicities, occuring in study participapants
  • Surgical morbidity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the surgical morbidity in patients undergoing pancreaticduodenectomy 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 biiomarkers of autophagy with hydroxychloroquine therapy and explore correlation with progression-free survival
  • Pathologic downstaging [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To determine pathlogic downstaging 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
Not Provided
Not Provided
 
Short Course Radiation Therapy With Proton or Photon Beam Capecitabine and Hydroxychloroquine for Resectable Pancreatic Cancer
Phase II Study of Neoadjuvant Accelerated Short Course Radiation Therapy With Proton or Photon RT Plus 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).

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Pancreatic Cancer
  • 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
Experimental: Hydroxychloroquine
Hydroxychloroquine with chemoradiation
Interventions:
  • Drug: Capecitabine
  • Drug: Hydroxychloroquine
  • Radiation: Proton or Photon Radiation Therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
Not Provided
July 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Theodore S Hong, MD 617-724-1159 tshong1@partners.org
United States
 
NCT01494155
11-073
Yes
Theodore Sunki Hong, Massachusetts General Hospital
Massachusetts General Hospital
Not Provided
Principal Investigator: Theodore S Hong, MD Massachusetts General Hospital
Massachusetts General Hospital
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP