Pancreatic Cancer
Conditions
Keywords
resectable pancreatic cancer, pancreaticoduodenectomy
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).
Interventions
DRUGCapecitabine
825 mg/m2 BID orally for a total of 10 days (M-F of weeks 2 and 3)
DRUGHydroxychloroquine
400 mg BID from study day 1 until surgery. Dosing resumed upon discharge from hospital
RADIATIONProton or Photon Radiation Therapy
Daily, beginning Week 2 for 5 consecutive days
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pathologic Complete Response | up to 9 weeks | Pathological complete response (pCR) will be defined as the absence of any viable tumor cells within the tissue samples removed during surgery. |
| Overall Survival | up to 4 years | Overall survival (OS) is defined as the time from start of study therapy to date of death and will be reported as the number of patients alive after 2 years and 4 years on study. Participants who have not died will be censored at the date they were last known to be alive. |
| Treatment-Emergent Adverse Events | 3 weeks | Treatment-emergent adverse events (TEAEs) are grade 3 or higher AEs as assessed by the CTEP Active Version of the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4, and at least possibly related to study treatment capecitabine + hydroxychloroquine and short course radiation therapy. TEAEs are AEs that began after the start of study treatment; or if the event was continuous from baseline and was serious, at least possibly related to study treatment, or resulted in death, discontinuation, or interruption or reduction of study treatment. Participants with multiple occurrences of TEAEs are counted only once per specific category in CTCAE v4. |
| Number of Participants With Surgical Morbidity | up to 30 days after surgery | Surgical morbidity is defined as adverse events during an operation and up to 30 days afterwards, grade 3 or higher and at least possibly related to surgery as assessed by the CTEP Active Version of the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4. |
| Number of Participants With Post-operative Mortality | 30 days after surgery | Post-operative mortality is defined as death within 30 days after surgery. |
| Number of Participants With Pathologic Downstaging | up to 9 weeks | Pathologic downstaging (pDS) is defined as a change in the tumor stage from pre-treatment clinical staging to the final pathology of the surgically removed tumor after receiving neoadjuvant treatment (i.e., treatment given before surgery). |
| Number of Participants With Local Control | Up to 2 years | Local control is defined as the time from the start of study treatment to the date of local failure; this outcome is reported below as the number of participants without local failure at 2 years after start of study treatment. Local failure is defined as progressive disease (PD) of the main tumor or at the margins of where the main tumor was surgically removed, as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 below: * At least a 20% increase in the longest diameter of target tumor lesion and an absolute increase of at least 5 mm, taking as reference the baseline measurement. * The appearance of one or more new lesions is also considered progression. Patients who have not experienced a local failure will be censored at the last date they were known to have local control. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJennifer Y. Wo, MD
Massachusetts General Hospital
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Between 50-59 years | 8 Participants |
| Age, Customized Between 60-69 years | 18 Participants |
| Age, Customized Between 70-79 years | 20 Participants |
| Age, Customized Between 80-89 years | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 39 / 50 |
| other Total, other adverse events | 50 / 50 |
| serious Total, serious adverse events | 20 / 50 |
Outcome results
None listed