Trial Outcomes & Findings for Gemcitabine Hydrochloride, and Radiation Therapy in Patients With Borderline Resectable Pancreatic Cancer (NCT NCT01897454)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Up to 30 months

Results posted on

2023-12-05

Participant Flow

Participants were enrolled into the study between 1/27/2012 and 04/24/2019.

Participant milestones

Participant milestones
Measure	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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Overall Study STARTED	23
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Overall Study Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride) n=22 Participants 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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Age, Continuous	63.5 years STANDARD_DEVIATION 7.8 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic White	4 Participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic Black	8 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	10 Participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants
Body Mass Index (BMI)	26.3 kg/m^2 STANDARD_DEVIATION 5.6 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 30 months

Population: Analytical results for the 18 participants who completed neoadjuvant (FOLFIRINOX) treatment

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 measures

Outcome measures
Measure	Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride) n=18 Participants 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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Percentage of Participants Achieving R0 Resection (R0 Resection Rate)	55.6 Percentage of Participants Interval 33.3 to 68.3

SECONDARY outcome

Timeframe: Up to 30 months

Population: Data related to the number of surgical adverse events was not collected and analyzed for the 15 participants who underwent surgical resection

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 measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 30 months

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 measures

Outcome measures
Measure	Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride) n=22 Participants 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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Toxicities Associated With Chemotherapy and Radiotherapy	22 Participants

SECONDARY outcome

Timeframe: Up to 60 months

Population: Median overall survival was determined for the 15 patients who received preoperative chemoradiotherapy and underwent pancreaticoduodenectomy

Median Overall Survival defined as the the duration of time from diagnosis to the time of death from any cause will be determined.

Outcome measures

Outcome measures
Measure	Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride) n=15 Participants 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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Overall Survival (OS)	35.1 Months Interval 18.4 to 78.5

SECONDARY outcome

Timeframe: Up to 30 months

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 measures

Outcome measures
Measure	Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride) n=22 Participants 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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Overall Response Rate	4 Participants

SECONDARY outcome

Timeframe: From start of treatment to time of progression, assessed up to 60 months

Population: Median overall survival was determined for the 15 patients who received preoperative chemoradiotherapy and underwent pancreaticoduodenectomy

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 measures

Outcome measures
Measure	Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride) n=15 Participants 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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Progression Free Survival (PFS)	34 Months Standard Error 9.81

SECONDARY outcome

Timeframe: Up to 30 months

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 measures

Outcome measures
Measure	Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride) n=22 Participants 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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Percentage of Patients Able to Undergo Resection	15 Participants

SECONDARY outcome

Timeframe: Up to 30 months

Population: 15 participants underwent pancreaticoduodenectomy

The percentage of patients who underwent pancreaticoduodenectomy requiring vascular reconstruction will be evaluated.

Outcome measures

Outcome measures
Measure	Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride) n=15 Participants 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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Vascular Reconstruction	5 Participants

Adverse Events

Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride)

Serious events: 4 serious events

Other events: 22 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride) n=22 participants at risk 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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Blood and lymphatic system disorders Thrombocytopenia	4.5% 1/22 • Number of events 1 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months
Blood and lymphatic system disorders Febrile Neutropenia	9.1% 2/22 • Number of events 2 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months
Blood and lymphatic system disorders Anemia	4.5% 1/22 • Number of events 1 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months

Other adverse events

Other adverse events
Measure	Treatment (FOLFIRINOX, IMRT, and Gemcitabine Hydrochloride) n=22 participants at risk 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. Fluorouracil: Given IV Gemcitabine Hydrochloride: Given IV Intensity-Modulated Radiation Therapy: Undergo IMRT Irinotecan Hydrochloride: Given IV Leucovorin Calcium: Given IV Oxaliplatin: Given IV
Blood and lymphatic system disorders Neutropenia	86.4% 19/22 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months
Blood and lymphatic system disorders Thrombocytopenia	90.9% 20/22 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months
Blood and lymphatic system disorders Anemia	45.5% 10/22 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months
General disorders Fatigue	86.4% 19/22 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months
Gastrointestinal disorders Nausea	50.0% 11/22 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months
Gastrointestinal disorders Diarrhea	50.0% 11/22 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months
Gastrointestinal disorders Vomiting	27.3% 6/22 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months
Gastrointestinal disorders Mucositis	22.7% 5/22 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months
Infections and infestations Hand-foot Syndrome	4.5% 1/22 • Up to 2-6 weeks following each cycle of chemoradiotherapy, up to 60 months

Additional Information

Dr. Jennifer Chuy

NYU Langone

Phone: 646-501-0194

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place