Brief Summary
This phase II trial studies how well combination chemotherapy, gemcitabine hydrochloride, and radiation therapy before surgery works in treating patients with pancreatic cancer that has not spread to other places in the body and can be removed by surgery. Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, irinotecan hydrochloride, oxaliplatin, and gemcitabine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Fluorouracil, irinotecan hydrochloride, and gemcitabine hydrochloride may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy and gemcitabine hydrochloride with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Brief Title
Gemcitabine Hydrochloride, and Radiation Therapy in Patients With Borderline Resectable Pancreatic Cancer
Detailed Description
PRIMARY OBJECTIVES:
I. To assess the efficacy, measured as the proportion of R0 resections, of fluorouracil-leucovorin calcium-irinotecan hydrochloride-oxaliplatin (FOLFIRINOX) chemotherapy regimen followed by gemcitabine based chemoradiotherapy when used as preoperative therapy in patients with borderline resectable adenocarcinoma of the pancreas.
SECONDARY OBJECTIVES:
I. To measure the overall response rate (ORR). II. To evaluate overall survival (OS). III. To evaluate progression free survival (PFS). IV. To evaluate safety and toxicity associated with chemotherapy and radiotherapy.
V. To assess adverse events related to surgery. VI. To assess the proportion of patients able to undergo resection. VII. To assess proportion of patients requiring vascular reconstruction.
OUTLINE:
CHEMOTHERAPY REGIMEN: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 90 minutes on day 1, and fluorouracil IV over 46 hours on days 1-3. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving disease progression proceed to chemoradiotherapy.
CHEMORADIOTHERAPY REGIMEN: Beginning 4-6 weeks after completion of chemotherapy, patients undergo intensity-modulated radiation therapy (IMRT) on 5 consecutive days per week for a total of 28 fractions and receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 30 months.
I. To assess the efficacy, measured as the proportion of R0 resections, of fluorouracil-leucovorin calcium-irinotecan hydrochloride-oxaliplatin (FOLFIRINOX) chemotherapy regimen followed by gemcitabine based chemoradiotherapy when used as preoperative therapy in patients with borderline resectable adenocarcinoma of the pancreas.
SECONDARY OBJECTIVES:
I. To measure the overall response rate (ORR). II. To evaluate overall survival (OS). III. To evaluate progression free survival (PFS). IV. To evaluate safety and toxicity associated with chemotherapy and radiotherapy.
V. To assess adverse events related to surgery. VI. To assess the proportion of patients able to undergo resection. VII. To assess proportion of patients requiring vascular reconstruction.
OUTLINE:
CHEMOTHERAPY REGIMEN: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 90 minutes on day 1, and fluorouracil IV over 46 hours on days 1-3. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving disease progression proceed to chemoradiotherapy.
CHEMORADIOTHERAPY REGIMEN: Beginning 4-6 weeks after completion of chemotherapy, patients undergo intensity-modulated radiation therapy (IMRT) on 5 consecutive days per week for a total of 28 fractions and receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 30 months.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Pancreatic Adenocarcinoma
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer
Stage III Pancreatic Cancer
Eligibility Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed adenocarcinoma of the pancreas
* Only patients that have not received any prior treatment for pancreas cancer are eligible for this treatment protocol
* Patients are not required to have measurable disease by traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria, as lesions in the pancreas are notoriously hard to measure radiographically; however, patients must have disease which is evaluable for resection
* Disease should be determined as "borderline resectable" according to the Expert Consensus Statement published by Callery et al:
* No distant metastasis
* Venous involvement of the superior mesenteric vein (SMV)/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction
* Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis
* Tumor abutment of the superior mesenteric artery (SMA) not to exceed greater than 180 degrees of the circumference of the vessel wall
* Life expectancy of greater than 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 80%)
* Leukocytes \>= 3,000/microliter (mcL)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 2 mg/dl
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal
* Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
* Ability to understand and the willingness to sign a written informed consent document
* Patients may not be receiving any other concurrent chemotherapy, immunotherapy, or radiotherapy
Exclusion Criteria:
* Patients who have had prior chemotherapy or radiotherapy for the treatment of pancreas cancer
* Patients may not be receiving any other investigational agents
* Evidence of extent of pancreatic cancer beyond that defined as "borderline resectable" above (locally advanced or distant disease); peripancreatic lymph node involvement, either confirmed or suspected, will not be considered distant disease unless the lymph node involvement extends outside of the field of resection
* Patients with known brain metastases should be excluded from this clinical trial
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, oxaliplatin, irinotecan or gemcitabine
* Any concurrent active malignancy other than non-melanoma skin cancers or carcinoma-in-situ of the cervix; patients with previous malignancies but without evidence of disease for \> 3 years will be allowed to enter the trial; patients with a history of a T1a or b prostate cancer (detected incidentally at transurethral resection of the prostate \[TURP\] and comprising less than 5% of resected tissue) may participate if the prostate-specific antigen (PSA) remained within normal limits since TURP removal
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
* Histologically or cytologically confirmed adenocarcinoma of the pancreas
* Only patients that have not received any prior treatment for pancreas cancer are eligible for this treatment protocol
* Patients are not required to have measurable disease by traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria, as lesions in the pancreas are notoriously hard to measure radiographically; however, patients must have disease which is evaluable for resection
* Disease should be determined as "borderline resectable" according to the Expert Consensus Statement published by Callery et al:
* No distant metastasis
* Venous involvement of the superior mesenteric vein (SMV)/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction
* Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis
* Tumor abutment of the superior mesenteric artery (SMA) not to exceed greater than 180 degrees of the circumference of the vessel wall
* Life expectancy of greater than 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 80%)
* Leukocytes \>= 3,000/microliter (mcL)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 2 mg/dl
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal
* Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
* Ability to understand and the willingness to sign a written informed consent document
* Patients may not be receiving any other concurrent chemotherapy, immunotherapy, or radiotherapy
Exclusion Criteria:
* Patients who have had prior chemotherapy or radiotherapy for the treatment of pancreas cancer
* Patients may not be receiving any other investigational agents
* Evidence of extent of pancreatic cancer beyond that defined as "borderline resectable" above (locally advanced or distant disease); peripancreatic lymph node involvement, either confirmed or suspected, will not be considered distant disease unless the lymph node involvement extends outside of the field of resection
* Patients with known brain metastases should be excluded from this clinical trial
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, oxaliplatin, irinotecan or gemcitabine
* Any concurrent active malignancy other than non-melanoma skin cancers or carcinoma-in-situ of the cervix; patients with previous malignancies but without evidence of disease for \> 3 years will be allowed to enter the trial; patients with a history of a T1a or b prostate cancer (detected incidentally at transurethral resection of the prostate \[TURP\] and comprising less than 5% of resected tissue) may participate if the prostate-specific antigen (PSA) remained within normal limits since TURP removal
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Inclusion Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed adenocarcinoma of the pancreas
* Only patients that have not received any prior treatment for pancreas cancer are eligible for this treatment protocol
* Patients are not required to have measurable disease by traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria, as lesions in the pancreas are notoriously hard to measure radiographically; however, patients must have disease which is evaluable for resection
* Disease should be determined as "borderline resectable" according to the Expert Consensus Statement published by Callery et al:
* No distant metastasis
* Venous involvement of the superior mesenteric vein (SMV)/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction
* Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis
* Tumor abutment of the superior mesenteric artery (SMA) not to exceed greater than 180 degrees of the circumference of the vessel wall
* Life expectancy of greater than 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 80%)
* Leukocytes \>= 3,000/microliter (mcL)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 2 mg/dl
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal
* Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
* Ability to understand and the willingness to sign a written informed consent document
* Patients may not be receiving any other concurrent chemotherapy, immunotherapy, or radiotherapy
* Histologically or cytologically confirmed adenocarcinoma of the pancreas
* Only patients that have not received any prior treatment for pancreas cancer are eligible for this treatment protocol
* Patients are not required to have measurable disease by traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria, as lesions in the pancreas are notoriously hard to measure radiographically; however, patients must have disease which is evaluable for resection
* Disease should be determined as "borderline resectable" according to the Expert Consensus Statement published by Callery et al:
* No distant metastasis
* Venous involvement of the superior mesenteric vein (SMV)/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction
* Gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis
* Tumor abutment of the superior mesenteric artery (SMA) not to exceed greater than 180 degrees of the circumference of the vessel wall
* Life expectancy of greater than 6 months
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 80%)
* Leukocytes \>= 3,000/microliter (mcL)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 2 mg/dl
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal
* Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
* Ability to understand and the willingness to sign a written informed consent document
* Patients may not be receiving any other concurrent chemotherapy, immunotherapy, or radiotherapy
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01897454
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2012-570
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase II Trial of Preoperative FOLFIRINOX Followed by Gemcitabine Based Chemoradiotherapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma
Primary Outcomes
Outcome Description
The percentage of participants achieving R0 resection, defined as the absence of gross and microscopic tumor involvement in the resection margins, will be determined for those participants who receive at least one cycle of FOLFIRINOX chemotherapy. A 90% confidence interval will be determined.
Outcome Measure
Percentage of Participants Achieving R0 Resection (R0 Resection Rate)
Outcome Time Frame
Up to 30 months
Secondary Ids
Secondary Id
NCI-2013-01213
Secondary Id
12-017
Secondary Id
5P30CA013330-42
Secondary Outcomes
Outcome Description
Adverse events related to surgical resection will be documented and evaluated using the Clavien-Dindo classification scale. The Clavien-Dindo Classification is used to rank the severity of a surgical complication with higher Grades indicative of more intense interventional therapy needed to correct the complication. Scale grades range from Grade I to Grade V. Grade I complications are usually mild and consist of any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic and radiological intervention. Grade II complications require pharmacological treatment with drugs other than such allowed for Grade I. Grade III complications require surgical, endoscopic, or radiological intervention, Grade IV are indicative of life-threatening complications requiring ICU management and Grade V signify death of patient.
Outcome Time Frame
Up to 30 months
Outcome Measure
Adverse Events Related to Surgery
Outcome Description
The number of patients who experienced treatment related adverse events will be determined for all patients who received at least one cycle of FOLFIRINOX chemotherapy. These events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Outcome Time Frame
Up to 30 months
Outcome Measure
Toxicities Associated With Chemotherapy and Radiotherapy
Outcome Description
Median Overall Survival defined as the the duration of time from diagnosis to the time of death from any cause will be determined.
Outcome Time Frame
Up to 60 months
Outcome Measure
Overall Survival (OS)
Outcome Description
Overall Response Rate, defined as the percentage of patients that achieved Partial Response (PR) or Complete Response (CR) as per the Response evaluation in solid tumors criteria, was assessed using RECIST Version 1.1 criteria. Complete Response (CR) is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Higher percentages of PR and CR are associated with more favorable outcomes
Outcome Time Frame
Up to 30 months
Outcome Measure
Overall Response Rate
Outcome Description
Progression-free Survival defined as the duration of time from start of treatment to time of disease progression will be analyzed. Median progression free survival will be presented.
Outcome Time Frame
From start of treatment to time of progression, assessed up to 60 months
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
The percentage of participants with resectable or borderline resectable disease to undergo resection will be determined. The ability for patients to complete preoperative therapy and undergo resection is correlated with more favorable overall survival outcomes.
Outcome Time Frame
Up to 30 months
Outcome Measure
Percentage of Patients Able to Undergo Resection
Outcome Description
The percentage of patients who underwent pancreaticoduodenectomy requiring vascular reconstruction will be evaluated.
Outcome Time Frame
Up to 30 months
Outcome Measure
Vascular Reconstruction
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Jennifer Chuy
Investigator Email
jchuy@montefiore.org
Investigator Phone
Categories Mesh Debug
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Endocrine System Cancers --- ENDOCRINE GLAND NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Endocrine System Cancers --- ENDOCRINE SYSTEM DISEASES
Diabetes --- ENDOCRINE SYSTEM DISEASES
Diabetes & Endocrine System --- ENDOCRINE SYSTEM DISEASES
MeSH Terms
PANCREATIC NEOPLASMS
DIGESTIVE SYSTEM NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
ENDOCRINE GLAND NEOPLASMS
DIGESTIVE SYSTEM DISEASES
PANCREATIC DISEASES
ENDOCRINE SYSTEM DISEASES
FLUOROURACIL
DEHYDROFTORAFUR
GEMCITABINE
RADIOTHERAPY, INTENSITY-MODULATED
IRINOTECAN
LEVOLEUCOVORIN
LEUCOVORIN
OXALIPLATIN
URACIL
PYRIMIDINONES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
RADIOTHERAPY, CONFORMAL
RADIOTHERAPY, COMPUTER-ASSISTED
RADIOTHERAPY
THERAPEUTICS
CAMPTOTHECIN
ALKALOIDS
FORMYLTETRAHYDROFOLATES
TETRAHYDROFOLATES
FOLIC ACID
PTERINS
PTERIDINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
COENZYMES
ENZYMES AND COENZYMES
COORDINATION COMPLEXES
ORGANIC CHEMICALS