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

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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

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

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

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

Original Estimated Enrollment ^ICMJE

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

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

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