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Combination Chemotherapy, Gemcitabine Hydrochloride, and Radiation Therapy Before Surgery in Treating Patients With Borderline Resectable Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01897454
Recruitment Status : Active, not recruiting
First Posted : July 12, 2013
Last Update Posted : August 17, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jennifer Chuy, Albert Einstein College of Medicine

Tracking Information
First Submitted Date  ICMJE July 9, 2013
First Posted Date  ICMJE July 12, 2013
Last Update Posted Date August 17, 2020
Study Start Date  ICMJE November 2012
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2013)
Proportion of R0 resection rate in participants receiving at least one cycle of FLOFIRINOX chemotherapy [ Time Frame: Up to 30 months ]
The R0 resection rate will be tested by one-sided one sample Z test for proportion with null hypothesis set at 40%.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2016)
  • Incidence of adverse events related to surgery [ Time Frame: Up to 30 months ]
    Will be tabulated.
  • Incidence of toxicities associated with chemotherapy and radiotherapy graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 months ]
    Will be tabulated.
  • OS [ Time Frame: Up to 30 months ]
    The overall survival rate in the study will be examined for survival probabilities using Kaplan-Meier procedure and association of clinical covariates with overall survival status will be examined using log-rank test and Cox regression procedure. Median overall survival with confidence interval will be presented. Brookmeyer and Crowley method will be used to estimate a 95% confidence interval for median OS.
  • Overall response rate (assessed by RECIST criteria) [ Time Frame: Up to 30 months ]
    Will be examined using one sample Z-test for proportion.
  • PFS [ Time Frame: From start of treatment to time of progression, assessed up to 30 months ]
    The time to progression will be analyzed using Kaplan-Meier procedure followed by log-rank tests and Cox regression model to investigate the association between clinical covariates and progression free survival. Median progression free survival will be presented. Brookmeyer and Crowley method will be used to estimate a 95% confidence interval for median PFS.
  • Proportion of patients able to undergo resection [ Time Frame: Up to 30 months ]
    Will be tabulated with appropriate 95% confidence interval.
  • Proportion of patients requiring vascular reconstruction [ Time Frame: Up to 30 months ]
    Will be tabulated with 95% confidence interval.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2013)
  • Overall response rate (assessed by RECIST criteria) [ Time Frame: Up to 30 months ]
    Will be examined using one sample Z-test for proportion.
  • OS [ Time Frame: Up to 30 months ]
    The overall survival rate in the study will be examined for survival probabilities using Kaplan-Meier procedure and association of clinical covariates with overall survival status will be examined using log-rank test and Cox regression procedure. Median overall survival with confidence interval will be presented. Brookmeyer and Crowley method will be used to estimate a 95% confidence interval for median OS.
  • PFS [ Time Frame: From start of treatment to time of progression, assessed up to 30 months ]
    The time to progression will be analyzed using Kaplan-Meier procedure followed by log-rank tests and Cox regression model to investigate the association between clinical covariates and progression free survival. Median progression free survival will be presented. Brookmeyer and Crowley method will be used to estimate a 95% confidence interval for median PFS.
  • Incidence of toxicities associated with chemotherapy and radiotherapy graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 months ]
    Will be tabulated.
  • Incidence of adverse events related to surgery [ Time Frame: Up to 30 months ]
    Will be tabulated.
  • Proportion of patients able to undergo resection [ Time Frame: Up to 30 months ]
    Will be tabulated with appropriate 95% confidence interval.
  • Proportion of patients requiring vascular reconstruction [ Time Frame: Up to 30 months ]
    Will be tabulated with 95% confidence interval.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy, Gemcitabine Hydrochloride, and Radiation Therapy Before Surgery in Treating Patients With Borderline Resectable Pancreatic Cancer
Official Title  ICMJE A Phase II Trial of Preoperative FOLFIRINOX Followed by Gemcitabine Based Chemoradiotherapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Pancreatic Adenocarcinoma
  • Stage IIA Pancreatic Cancer
  • Stage IIB Pancreatic Cancer
  • Stage III Pancreatic Cancer
Intervention  ICMJE
  • Drug: Fluorouracil
    Given IV
    Other Names:
    • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
    • 5-Fluorouracil
    • 5-Fluracil
    • 5-FU
    • AccuSite
    • Carac
    • Fluoro Uracil
    • Fluouracil
    • Flurablastin
    • Fluracedyl
    • Fluracil
    • Fluril
    • Fluroblastin
    • Ribofluor
    • Ro 2-9757
    • Ro-2-9757
  • Drug: Gemcitabine Hydrochloride
    Given IV
    Other Names:
    • dFdCyd
    • Difluorodeoxycytidine Hydrochloride
    • Gemzar
    • LY-188011
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
    Other Names:
    • IMRT
    • Intensity Modulated RT
    • Intensity-Modulated Radiotherapy
  • Drug: Irinotecan Hydrochloride
    Given IV
    Other Names:
    • Campto
    • Camptosar
    • Camptothecin 11
    • Camptothecin-11
    • CPT 11
    • CPT-11
    • Irinomedac
    • U-101440E
  • Drug: Leucovorin Calcium
    Given IV
    Other Names:
    • Adinepar
    • Calcifolin
    • Calcium (6S)-Folinate
    • Calcium Folinate
    • Calcium Leucovorin
    • Calfolex
    • Calinat
    • Cehafolin
    • Citofolin
    • Citrec
    • Citrovorum Factor
    • Cromatonbic Folinico
    • Dalisol
    • Disintox
    • Divical
    • Ecofol
    • Emovis
    • Factor, Citrovorum
    • Flynoken A
    • Folaren
    • Folaxin
    • FOLI-cell
    • Foliben
    • Folidan
    • Folidar
    • Folinac
    • Folinate Calcium
    • folinic acid
    • Folinic Acid Calcium Salt Pentahydrate
    • Folinoral
    • Folinvit
    • Foliplus
    • Folix
    • Imo
    • Lederfolat
    • Lederfolin
    • Leucosar
    • leucovorin
    • Rescufolin
    • Rescuvolin
    • Tonofolin
    • Wellcovorin
  • Drug: Oxaliplatin
    Given IV
    Other Names:
    • 1-OHP
    • Ai Heng
    • Aiheng
    • Dacotin
    • Dacplat
    • Diaminocyclohexane Oxalatoplatinum
    • Eloxatin
    • Eloxatine
    • JM-83
    • Oxalatoplatin
    • Oxalatoplatinum
    • RP 54780
    • RP-54780
    • SR-96669
Study Arms  ICMJE Experimental: Treatment (FOLFIRINOX, IMRT, and gemcitabine hydrochloride)

CHEMOTHERAPY REGIMEN: Patients receive oxaliplatin 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 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.

Interventions:
  • Drug: Fluorouracil
  • Drug: Gemcitabine Hydrochloride
  • Radiation: Intensity-Modulated Radiation Therapy
  • Drug: Irinotecan Hydrochloride
  • Drug: Leucovorin Calcium
  • Drug: Oxaliplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 13, 2020)
24
Original Estimated Enrollment  ICMJE
 (submitted: July 9, 2013)
50
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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/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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01897454
Other Study ID Numbers  ICMJE 2012-570
NCI-2013-01213 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
12-017
2012-570 ( Other Identifier: Montefiore Medical Center-Weiler Hospital )
P30CA013330 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jennifer Chuy, Albert Einstein College of Medicine
Study Sponsor  ICMJE Albert Einstein College of Medicine
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Jennifer Chuy Montefiore Medical Center-Weiler Hospital
PRS Account Albert Einstein College of Medicine
Verification Date August 2020

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