Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer

Pancreatic Cancer Clinical Trial

Official title:

Phase I/II Study of Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00889187
• Other study ID #: 08-375
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: December 2009
• Est. completion date: December 30, 2011

Study information

• Verified date: April 2018
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this research study is to determine if it is possible to deliver high dose radiation in one week while also giving the drug capecitabine for the treatment of pancreatic cancer prior to surgery, to determine if this treatment can be given safely for the treatment of pancreatic cancer prior to surgery and, to determine if this treatment can improve the local control pancreatic cancer prior to surgery compared to historical controls of standard treatment.

Description:

OBJECTIVES:

Primary

• Phase I: To determine the feasibility and tolerability of radiation therapy for pancreatic cancer delivered with high dose external beam radiation in a one week accelerated schedule with concurrent capecitabine

• Phase II: To demonstrate a grade 3 or greater (any) toxicity rate of less than 20%

Secondary

• To determine local control and recurrence patterns of pancreatic cancer relative to a standard regimen of 50.4 Gy as seen in historical controls

• To determine the pathologic response rate

• To determine the progression-free survival

• To determine the surgical morbidity

• To determine 30-day post-operative mortality after pancreatic resection

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: December 30, 2011
• Est. primary completion date: December 30, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cytologic or histologic proof of pancreatic ductal carcinoma is required prior to treatment.

• No evidence of metastatic disease as determined by chest CT scan, abdominal CT scan (or MRI with gadolinium and/or manganese), and all patients must be staged with a physical exam, chest CT, and abdominal CT with intravenous contrast.

• Only potentially resectable patients are eligible. Potentially resectable is defined as: a)no extrapancreatic disease, b)no evidence (on CT) of involvement of the celiac axis or superior mesenteric artery, and c)no evidence (on CT or MRI) of occlusion of the superior mesenteric vein or superior mesenteric-portal venous confluence.

• 18 years of age or older

• ECOG Performance status of 0 or 1

• Women of child bearing potential must practice adequate contraception and to refrain from breast feeding. Female patients must have a negative pregnancy test within 7 days of treatment

• Lab values as specified in the protocol

Exclusion Criteria:

• Patients cannot have hepatic or peritoneal metastases detected by imaging or laparoscopy prior to chemoradiation

• Serious concomitant systemic disorders incompatible with the study, such as significant cardiac or pulmonary morbidity, or ongoing infection as manifested by fever

• Pregnant or lactating women

• Life expectancy < 3 months

• Serious, uncontrolled, concurrent infection(s)

• Any prior chemotherapy or radiation for treatment of the patient's pancreatic tumor

• Treatment for other cancers within the last five years, except cured non-melanoma skin cancer and treated in situ cervical cancer

• Clinically significant cardiac disease or myocardial infarction within the last 12 months

• Other serious uncontrolled medical conditions that the investigator feels might compromise study participation

• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome

• Known, existing uncontrolled coagulopathy

• Unwillingness to participate or inability to comply with the protocol for the duration of the study

• Any prior 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 judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake

• Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery

• Patients should not be on cimetidine as it can decrease the clearance of 5-FU. Another H2-blocker or proton pump inhibitor may be substituted before study entry

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Radiation:
• Neoadjuvant Short-Course Photon Radiation

Drug:
• Capecitabine

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Brigham and Women's Hospital, Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

Wo JY, Mamon HJ, Ferrone CR, Ryan DP, Blaszkowsky LS, Kwak EL, Tseng YD, Napolitano BN, Ancukiewicz M, Swanson RS, Lillemoe KD, Fernandez-del Castillo C, Hong TS. Phase I study of neoadjuvant accelerated short course radiation therapy with photons and cap — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neoadjuvant Short-Course Photon Radiation Therapy Maximum Tolerated Dose (MTD) [Phase I]	Neoadjuvant short-course photon radiation therapy MTD in combination with capecitabine 825 mg/m2 orally BID for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If none of 3 initial patients or only 1 of 6 patients have a DLT on dose level 3 then 6 additional patients are treated at this dose. If during this expansion, the rate of DLT exceeds 30% then the next lower dose level is declared the MTD. If no DLTs are observed, the MTD is not reached.	within 3 weeks of the start of chemoradiation therapy
Primary	Dose Limiting Toxicity (DLT) [Phase I]	DLT occurring within 3 weeks of the start of chemoradiation therapy was defined as: Grade 3 non-hematologic or hematologic toxicity requiring interruption of >7 days (d) of chemo or >3d chemoradiation; Grade 4 non-hematologic; Grade 4 neutropenia or thrombocytopenia; Treatment-related death; Delays in surgery >3 weeks due to treatment-related toxicity. A 30% increase in any surgical complication rate beyond those previously established rates (readmission rate: 16%; pancreatic fistula/intra-abdominal abscess/infection rate: 27%, major intra-abdominal bleeding requiring return to OR: 1.6%, delayed gastric emptying: 4.4%, and superficial wound infection rate: 8%) was also considered a DLT.	within 3 weeks of the start of chemoradiation therapy
Primary	Grade 3-5 Toxicity Rate [Phase II]	All Grade 3-5 events based on CTCAEv3 related to the accelerated dose (attribution possible, probable, definite) as reported on case report forms.	within 3 weeks of the start of chemoradiation therapy
Secondary	Local Recurrence Rate [Phase II]	Local recurrence rate is defined as the proportion of patients with evidence of tumor recurrence within the radiation field based on RECIST criteria. Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.	Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.
Secondary	Pathologic Response Rate [Phase II]	Pathologic response rate is the proportion of patients with the pathologic specimen absent any viable tumor cell. Pathological review of the pancreaticoduodenectomy specimen will be performed according to the AJCC Staging Classification, 6th edition. Initial gross evaluation and identification of resection margins will be performed jointly by the surgeon and the pathologist.	Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
Secondary	Progression-Free Survival (PFS) [Phase II]	Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Patients alive whose disease had not progressed are censored at date of last disease evaluation	Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.
Secondary	Surgical Morbidity Rate [Phase II]	The proportion of patients experienced any grade 3-4 adverse event based on CTCAEv3 related to the surgery (attribution possible, probable, definite) as reported on case report forms.	Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
Secondary	Surgical Mortality Rate [Phase II]	The proportion of patients with a death related to the surgery (CTCAEv3 attribution possible, probable, definite).	Assessed up to 30 days after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy