A Phase II Study of Neoadjuvant FOLFIRINOX | NCT02178709

NCT02178709

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
FOLFIRINOX	Experimental	FOLFIRINOX consists of the following combination of drugs: Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle Irinotecan, 180 mg/m2, IV over 90 minutes with leucovorin, administered on days 1 and 15 of each 28 day cycle 5 FU, 400 mg/m2, IV bolus over 2 minutes after irinotecan, administered on days 1 and 15 of each 28 day cycle. 5FU, 2400 mg/m2, IV infusion over 46 hours after 5FU bolus injection, administered on days 1 and 15 of each 28 day cycle.	Drug: FOLFIRINOX

Interventions

Name	Type	Description	Arm Group Labels	Other Names
FOLFIRINOX	Drug	FOLFIRINOX consists of the following combination of drugs: Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle Irinotecan, 180 mg/m2, IV over 90 minutes with leucovorin, administered on days 1 and 15 of each 28 day cycle 4.5 FU, 400 mg/m2, IV bolus over 2 minutes after irinotecan, administered on days 1 and 15 of each 28 day cycle. 5.5FU, 2400 mg/m2, IV infusion over 46 hours after 5FU bolus injection, administered on days 1 and 15 of each 28 day cycle.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Patients With Pathologic Complete Response	Pathologic complete response was evaluated using MRI or CT and Evan's criteria for pathologic response following neoadjuvant therapy: I: <10% to no tumor cells destroyed IIa: 10-50% of tumor cells destroyed IIb: 50-90% of tumor cells destroyed III: >90% of tumor cells destroyed IIIM: sizable pools of cellular mucin IV: No viable tumor cells (complete pathologic response) IVM: Acellular pools of mucin	Up to 4 months

Secondary Outcomes

Measure	Description	Time Frame
Number of Patients With Treatment-Related Adverse Events Grade 3 or Above	Number of unique patients who had a treatment-related (possible, probable, or definite) adverse event with grade 3 or greater using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.	Every 15 days for approximately 6 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

≥ 18 years old at the time of informed consent
Able to provide written informed consent and HIPAA authorization
ECOG performance status of 0 or 1
Patient must be eligible for abdominal surgery
Histologically confirmed adenocarcinoma of the pancreas that has been documented to be resectable by standardized radiographic criteria by a pancreatic surgeon
Patients must to have tumor tissue collected prior to enrolling on this trial. Up to 10 patients will be accepted with no pre-treatment research tissue collection or tissue collection from an outside institution.

a.If the tissue is from an outside institution, it must be reviewed at Indiana University Health Pathology Department if a biopsy was performed outside of this institution.
Women of childbearing potential definition (WOCBP) must have a negative serum or urine pregnancy test performed within 14 days prior to initiation of FOLFIRINOX.

Any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) is classified as WOCBP if she meets the following criteria:
1. Has not undergone a hysterectomy or bilateral oophorectomy; or
2. Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
WOCBP and men must agree to use adequate contraception prior, to study entry, for the duration of study participation, and 8 weeks after the end of treatment.
Patients must have adequate organ function as defined by the following laboratory values at study entry:
1. Hemoglobin ≥ 9 g/dL (transfusions are acceptable)
2. ANC ≥ 1.5 x 109/L
3. Platelets ≥ 100 x 109/L
4. Creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 50 mL/min (estimated by Cockcroft-Gault or measured)
5. Total bilirubin ≤ 1.5 x ULN
6. AST/ALT ≤ 3 x ULN

Exclusion Criteria:

Prior therapy for pancreatic adenocarcinoma
Other malignancies within the past 3 years except for the following: adequately treated cervical or vulvar carcinoma in situ, treated basal cell or squamous carcinoma of the skin, superficial bladder tumors (Ta, Tis & T1), ductal carcinoma in situ (DCIS) of the breast and low grade prostate cancer. Any cancer curatively treated >3 years prior to entry with no clinical evidence of recurrence is permitted.
Hypersensitivity to 5FU, oxaliplatin (or other platinum agents), irinotecan (or to their excipients).
Participation in any investigational drug study within 4 weeks preceding the start of study treatment. Patients are not permitted to participate in another investigational drug study while being treated on this protocol.
Inability to receive a port or PICC line.
History of or suspected Gilbert's Disease (testing not required if presence is not suspected).
Baseline peripheral neuropathy/paresthesia grade ≥ 1.
Active hepatitis B, unless patient has been on antiviral agents for at least 2 months (baseline testing not required).
Active clinically serious infections (> grade 2).
Major surgery or significant traumatic injury within 8 weeks of first study drug. A core pancreatic or liver biopsy does not preclude the patient from the study.
Unable or unwilling to discontinue use of ketoconazole or St John's wort. Use of phenytoin, carbamazepine, phenobarbital, rifampin and rifabutin is discouraged, but not contraindicated. If patients require phenytoin, carbamazepine or phenobarbital monitoring of drug levels is suggested during the study.
Pregnant or lactating women.
Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Name	Affiliation	Role
Michael House, M.D.	Indiana University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Indiana University Simon Cancer Center		Indianapolis	Indiana	46202	United States

ID	Title	Description
FG000	FOLFIRINOX	FOLFIRINOX consists of the following combination of drugs: Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle Irinotecan, 180 mg/m2, IV over 90 minutes with leucovorin, administered on days 1 and 15 of each 28 day cycle 4.5 FU, 400 mg/m2, IV bolus over 2 minutes after irinotecan, administered on days 1 and 15 of each 28 day cycle. 5.5FU, 2400 mg/m2, IV infusion over 46 hours after 5FU bolus injection, administered on days 1 and 15 of each 28 day cycle.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	FOLFIRINOX	FOLFIRINOX consists of the following combination of drugs: Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle Irinotecan, 180 mg/m2, IV over 90 minutes with leucovorin, administered on days 1 and 15 of each 28 day cycle 4.5 FU, 400 mg/m2, IV bolus over 2 minutes after irinotecan, administered on days 1 and 15 of each 28 day cycle. 5.5FU, 2400 mg/m2, IV infusion over 46 hours after 5FU bolus injection, administered on days 1 and 15 of each 28 day cycle.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Patients With Pathologic Complete Response

Pathologic complete response was evaluated using MRI or CT and Evan's criteria for pathologic response following neoadjuvant therapy:

I: <10% to no tumor cells destroyed IIa: 10-50% of tumor cells destroyed IIb: 50-90% of tumor cells destroyed III: >90% of tumor cells destroyed IIIM: sizable pools of cellular mucin IV: No viable tumor cells (complete pathologic response) IVM: Acellular pools of mucin

All patients who received at least two doses of FOLFIRINOX (unless treatment-related toxicity precluded additional doses) and had at least one post-baseline assessment or died before any evaluation.

Posted

Number

95% Confidence Interval

percentage of participants

Up to 4 months

ID	Title	Description
OG000	FOLFIRINOX	FOLFIRINOX consists of the following combination of drugs: Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle Irinotecan, 180 mg/m2, IV over 90 minutes with leucovorin, administered on days 1 and 15 of each 28 day cycle 4.5 FU, 400 mg/m2, IV bolus over 2 minutes after irinotecan, administered on days 1 and 15 of each 28 day cycle. 5.5FU, 2400 mg/m2, IV infusion over 46 hours after 5FU bolus injection, administered on days 1 and 15 of each 28 day cycle.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	FOLFIRINOX	FOLFIRINOX consists of the following combination of drugs: Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle Irinotecan, 180 mg/m2, IV over 90 minutes with leucovorin, administered on days 1 and 15 of each 28 day cycle 5 FU, 400 mg/m2, IV bolus over 2 minutes after irinotecan, administered on days 1 and 15 of each 28 day cycle. 5FU, 2400 mg/m2, IV infusion over 46 hours after 5FU bolus injection, administered on days 1 and 15 of each 28 day cycle.

ID	Term
C000627770	folfirinox
D000077150	Oxaliplatin
D002955	Leucovorin
D000077146	Irinotecan
D005472	Fluorouracil

ID	Term
D056831	Coordination Complexes
D009930	Organic Chemicals
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates