Preoperative Folfirinox for Resectable Pancreatic Adenocarcinoma - A Phase II Study

• Sponsor: Case Comprehensive Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02345460
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial studies how well combination chemotherapy works in treating patients with pancreatic cancer before undergoing surgery. Drugs used in chemotherapy, such as irinotecan hydrochloride, oxaliplatin, leucovorin calcium, and fluorouracil (FOLFIRINOX), work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Adenocarcinoma; Poorly Differentiated Malignant Neoplasm; Resectable Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Undifferentiated Pancreatic Carcinoma	Drug: Irinotecan Hydrochloride; Drug: Oxaliplatin; Drug: Leucovorin Calcium; Drug: Fluorouracil; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine feasibility of preoperative FOLFIRINOX for resectable pancreatic adenocarcinoma.

SECONDARY OBJECTIVES:

1. To determine safety and toxicity of preoperative FOLFIRINOX. II. To determine response rate. III. To determine proportion achieving major pathologic response - per College of American Pathologists (CAP) criteria.

2. To determine proportion achieving R0 resection. V. To determine perioperative (30-day) mortality. VI. To determine the role of cancer antigen (CA)19.9 as potential prognostic and/or predictive biomarker.

3. To determine progression-free survival. VIII. To determine overall survival.

OUTLINE:

Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride intravenously (IV) over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Preoperative Folfirinox for Resectable Pancreatic Adenocarcinoma - A Phase II Study
• Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (FOLFIRINOX) Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: Irinotecan Hydrochloride; Given IV; Drug: Oxaliplatin; Given IV; Drug: Leucovorin Calcium; Given IV; Other Names: CF ; Drug: Fluorouracil; Given IV; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Number of Patients Undergoing Surgical Resection After Receiving at Least 4 of the 6 Courses of Preoperative Chemotherapy [Up to 12 weeks]

   Proportion will be estimated using a binomial test.

Secondary Outcome Measures

1. Progression-free Survival [Up to 2 years]

   Time from enrollment to the earlier of death or disease progression. Will be estimated with Kaplan Meier curves.

2. Overall Survival [Up to 2 years]

   Time from enrollment to death from any cause. Will be estimated with Kaplan Meier curves.

3. Incidence of Toxicities Greater Than Grade 2, Using the Common Terminology Criteria for Adverse Events Version 4.0 [Up to 30 days after end of treatment or to the day prior to surgery]

   Toxicity evaluation will be enumeration of all major toxicities, with proportions calculated for each.

4. Response Rate Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1 [Up to 2 years]

   Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.

5. Number of Participants Achieving Major Pathologic Response [Up to 2 years]

   Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.

6. Number of Participants Achieving R0 Resection [Up to 2 years]

   Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.

7. Number of Participants Experiencing Perioperative (30-day) Mortality [Up to 30 days]

   Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed carcinoma of the pancreas; most cases will be adenocarcinoma; cases with "undifferentiated" or "poorly differentiated" carcinoma will also be eligible

• There should be no evidence of metastatic disease on imaging of the chest, abdomen, and pelvis; this imaging should be either a contrast-enhanced computed tomography (CT) scan, or a contrast-enhanced magnetic resonance imaging (MRI) scan; positron emission tomography (PET) scans alone will not be adequate alternatives; there should be no evidence of occult metastatic disease in the abdomen, confirmed by laparoscopic examination

• The primary tumor must be resectable, defined as no involvement (abutment or encasement) of the major arteries (celiac, common hepatic, superior mesenteric) and interface between tumor and vessel (portal, superior mesenteric veins) wall to be less than 180 degrees of the circumference of the vessel wall; this should be confirmed by imaging of the abdomen, either by a contrast-enhanced computed tomography (CT) scan, or a contrast-enhanced magnetic resonance imaging (MRI) scan; PET scans will not be adequate alternatives; for each patient, the resectability must be reviewed by one of the study surgeons

• Patient must not have received any cancer-directed therapy (e.g., surgery, chemotherapy, radiation therapy, biologic therapy) for the index diagnosis

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Hemoglobin >= 10.0 g/dl

• Absolute neutrophil count >= 1,500/mm^3

• Platelet count >= 100,000/mm^3

• Total bilirubin =< 1.5 X institutional upper limit of normal

• Serum creatinine within normal institutional limits, or creatinine clearance (calculated by Cockcroft-Gault) >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

• Women of child-bearing potential and men must agree to use adequate contraception (double-barrier method of birth control or abstinence) for the duration of study participation and for 6 months after completing chemotherapy; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately

• Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients with 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 or breastfeeding women

• Pre-existing peripheral neuropathy (grade I or higher)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Case Comprehensive Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Davendra Sohal, Case Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT02345460
• Other Study ID Numbers: CASE4214; NCI-2014-02277; CASE4214; P30CA043703
• First Posted: Jan 26, 2015
• Last Update Posted: Jul 13, 2018
• Last Verified: Jun 1, 2018

• Additional relevant MeSH terms: Adenocarcinoma; Pancreatic Neoplasms; Neoplasms; Leucovorin; Fluorouracil; Oxaliplatin; Irinotecan; Calcium; Levoleucovorin

Study Results

Participant Flow

Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	1 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Undergoing Surgical Resection After Receiving at Least 4 of the 6 Courses of Preoperative Chemotherapy
Description	Proportion will be estimated using a binomial test.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.

Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	0

2. Secondary Outcome

Title	Progression-free Survival
Description	Time from enrollment to the earlier of death or disease progression. Will be estimated with Kaplan Meier curves.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.

Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	0

3. Secondary Outcome

Title	Overall Survival
Description	Time from enrollment to death from any cause. Will be estimated with Kaplan Meier curves.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Only 1 patient was enrolled on study. Outcome data was not analyzed.

Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	0

4. Secondary Outcome

Title	Incidence of Toxicities Greater Than Grade 2, Using the Common Terminology Criteria for Adverse Events Version 4.0
Description	Toxicity evaluation will be enumeration of all major toxicities, with proportions calculated for each.
Time Frame	Up to 30 days after end of treatment or to the day prior to surgery

Outcome Measure Data

Analysis Population Description

Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.

Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	0

5. Secondary Outcome

Title	Response Rate Assessed Using Response Evaluation Criteria in Solid Tumors Version 1.1
Description	Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.

Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	0

6. Secondary Outcome

Title	Number of Participants Achieving Major Pathologic Response
Description	Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.

Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	0

7. Secondary Outcome

Title	Number of Participants Achieving R0 Resection
Description	Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.

Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	0

8. Secondary Outcome

Title	Number of Participants Experiencing Perioperative (30-day) Mortality
Description	Will be calculated as a binary outcome. Exact 95% confidence intervals will be calculated for binary outcomes.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

Only 1 patient was enrolled on study. Outcome data was not analyzed. Trial closed due to competing studies.

Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	0

Adverse Events

Time Frame	4 months
Arm/Group Title	Treatment (FOLFIRINOX)
Arm/Group Description	Patients receive FOLFIRINOX regimen comprising irinotecan hydrochloride IV over 90 minutes, oxaliplatin IV over 120 minutes, leucovorin calcium IV over 120 minutes, and fluorouracil IV over 1-2 minutes and then continuously over 46 hours on day 1. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Irinotecan Hydrochloride: Given IV Oxaliplatin: Given IV Leucovorin Calcium: Given IV Fluorouracil: Given IV Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Treatment (FOLFIRINOX)
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Treatment (FOLFIRINOX)
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (FOLFIRINOX)
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.