Phase II Study of Neoadjuvant Accelerated Short Course Radiation Therapy With Proton or Photon RT Plus Capecitabine and Hydroxychloroquine for Resectable Pancreatic Cancer
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Progression-free survival
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Hydroxychloroquine
Hydroxychloroquine with chemoradiation
Intervention: Proton or Photon Radiation Therapy (Radiation)
Hydroxychloroquine
Hydroxychloroquine with chemoradiation
Intervention: Capecitabine (Drug)
Hydroxychloroquine
Hydroxychloroquine with chemoradiation
Intervention: Hydroxychloroquine (Drug)
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: 2 years
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: up to 4 years
Progression-free survival (PFS) will be defined as the time from the start of treatment until the first objective documentation of progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) criteria, or death. PFS is reported as the number of participants without PD after 2 years and 4 years on study. Participants who die without a reported prior progression will be considered to have progressed on the day of their death. Progressive disease (PD) is defined as at least a 20% increase in the sum of longest the diameters of target lesions, taking as reference the baseline sum diameters. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
Secondary Outcomes
- Biomarkers(2 years)
- Pathologic down-staging(2 years)
- Local control(2 years)
- Describe QoL(2 Years)
- Measure utilization of health services(2 years)
- Pathologic response rate(2 years)
- Overall survival(2 years)
- Surgical morbidity(2 years)
- Post-operative Mortality(2 weeks)
- Toxicity/Adverse events(2 years)
- Number of Participants With Pathologic Complete Response(up to 9 weeks)
- Overall Survival(up to 4 years)
- Treatment-Emergent Adverse Events(3 weeks)
- Number of Participants With Surgical Morbidity(up to 30 days after surgery)
- Number of Participants With Post-operative Mortality(30 days after surgery)
- Number of Participants With Pathologic Downstaging(up to 9 weeks)
- Number of Participants With Local Control(Up to 2 years)
Investigators
Jennifer Wo
Radiation Oncologist
Massachusetts General Hospital