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Gemcitabine Hydrochloride, and Radiation Therapy in Patients With Borderline Resectable Pancreatic Cancer

Primary Purpose

Pancreatic Adenocarcinoma, Stage IIA Pancreatic Cancer, Stage IIB Pancreatic Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Fluorouracil

Gemcitabine Hydrochloride

Intensity-Modulated Radiation Therapy

Irinotecan Hydrochloride

Leucovorin Calcium

Oxaliplatin

About this trial

This is an interventional treatment trial for Pancreatic Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Montefiore Medical Center-Weiler Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (FOLFIRINOX, IMRT, and gemcitabine hydrochloride)

Arm Description

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.

Outcomes

Primary Outcome Measures

Proportion of R0 resection rate in participants receiving at least one cycle of FLOFIRINOX chemotherapy

The R0 resection rate will be tested by one-sided one sample Z test for proportion with null hypothesis set at 40%.

Secondary Outcome Measures

Incidence of adverse events related to surgery

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

Will be tabulated.

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)

Will be examined using one sample Z-test for proportion.

PFS

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

Will be tabulated with appropriate 95% confidence interval.

Proportion of patients requiring vascular reconstruction

Will be tabulated with 95% confidence interval.

Full Information

NCT ID

NCT01897454

First Posted

July 9, 2013

Last Updated

July 29, 2022

Sponsor

Albert Einstein College of Medicine

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01897454

Brief Title

Gemcitabine Hydrochloride, and Radiation Therapy in Patients With Borderline Resectable Pancreatic Cancer

Official Title

A Phase II Trial of Preoperative FOLFIRINOX Followed by Gemcitabine Based Chemoradiotherapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Terminated

Why Stopped

Study was terminated due to slower than anticipated accrual.

Study Start Date

November 2012 (undefined)

Primary Completion Date

November 1, 2021 (Actual)

Study Completion Date

November 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Albert Einstein College of Medicine

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Adenocarcinoma, Stage IIA Pancreatic Cancer, Stage IIB Pancreatic Cancer, Stage III Pancreatic Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (FOLFIRINOX, IMRT, and gemcitabine hydrochloride)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Fluorouracil

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Gemcitabine Hydrochloride

Other Intervention Name(s)

dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

Intensity-Modulated Radiation Therapy

Other Intervention Name(s)

IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Intervention Description

Undergo IMRT

Intervention Type

Drug

Intervention Name(s)

Irinotecan Hydrochloride

Other Intervention Name(s)

Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, U-101440E

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Leucovorin Calcium

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Other Intervention Name(s)

1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Proportion of R0 resection rate in participants receiving at least one cycle of FLOFIRINOX chemotherapy

Description

The R0 resection rate will be tested by one-sided one sample Z test for proportion with null hypothesis set at 40%.

Time Frame

Up to 30 months

Secondary Outcome Measure Information:

Title

Incidence of adverse events related to surgery

Description

Will be tabulated.

Time Frame

Up to 30 months

Title

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

Description

Will be tabulated.

Time Frame

Up to 30 months

Title

Description

Time Frame

Up to 30 months

Title

Overall response rate (assessed by RECIST criteria)

Description

Will be examined using one sample Z-test for proportion.

Time Frame

Up to 30 months

Title

PFS

Description

Time Frame

From start of treatment to time of progression, assessed up to 30 months

Title

Proportion of patients able to undergo resection

Description

Will be tabulated with appropriate 95% confidence interval.

Time Frame

Up to 30 months

Title

Proportion of patients requiring vascular reconstruction

Description

Will be tabulated with 95% confidence interval.

Time Frame

Up to 30 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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/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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jennifer Chuy

Organizational Affiliation

Montefiore Medical Center-Weiler Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Montefiore Medical Center-Weiler Hospital

City

Bronx

State/Province

New York

ZIP/Postal Code

10461

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

36221952

Citation

Acuna-Villaorduna A, Shankar V, Wysota M, Jirgal A, Kabarriti R, Bellemare S, Goldman I, Kaubisch A, Aparo S, Goel S, Chuy J. Induction Chemotherapy With FOLFIRINOX Followed by Chemoradiation With Gemcitabine in Patients With Borderline-Resectable Pancreatic Ductal Adenocarcinoma. Cancer Control. 2022 Jan-Dec;29:10732748221134411. doi: 10.1177/10732748221134411.

Results Reference

derived

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Gemcitabine Hydrochloride, and Radiation Therapy in Patients With Borderline Resectable Pancreatic Cancer

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