Trial Outcomes & Findings for A Phase II Study of Neoadjuvant FOLFIRINOX (NCT NCT02178709)

Last Updated: 2022-04-19

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

48 participants

Primary outcome timeframe

Up to 4 months

Results posted on

2022-04-19

Participant Flow

Participant milestones

Participant milestones
Measure	FOLFIRINOX FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Overall Study STARTED	48
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	FOLFIRINOX FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Overall Study Adverse Event	5
Overall Study Death	2
Overall Study Withdrawal by Subject	2
Overall Study Physician Decision	2
Overall Study Disease Progression	5

Baseline Characteristics

A Phase II Study of Neoadjuvant FOLFIRINOX

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FOLFIRINOX n=48 Participants FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants
Age, Categorical >=65 years	26 Participants n=5 Participants
Age, Continuous	62.9 years STANDARD_DEVIATION 9.19 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	43 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 4 months

Population: 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.

Outcome measures

Outcome measures
Measure	FOLFIRINOX n=43 Participants FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Percentage of Patients With Pathologic Complete Response	0 percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Every 15 days for approximately 6 months

Population: All patients who received at least one dose of FOLFIRINOX.

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.

Outcome measures

Outcome measures
Measure	FOLFIRINOX n=48 Participants FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Number of Patients With Treatment-Related Adverse Events Grade 3 or Above	14 Participants

SECONDARY outcome

Timeframe: Up to 4 months

The percentage of patients who successfully underwent surgery after neoadjuvant FOLFIRINOX and its 95% confidence interval will be provided.

Outcome measures

Outcome measures
Measure	FOLFIRINOX n=43 Participants FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Percentage of Patients Who Successfully Underwent Surgery After Neoadjuvant FOLFIRINOX	76.7 percentage of participants Interval 64.1 to 89.4

SECONDARY outcome

Timeframe: Up to 4 months

Population: All patients who completed surgery.

The percentage of patients with a final margin status of R0 after resection of their primary tumor and its 95% confidence interval will be provided. R0 resection indicates a microscopically margin-negative resection, in which no cancer cells seen microscopically at the primary tumor site.

Outcome measures

Outcome measures
Measure	FOLFIRINOX n=33 Participants FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Rate of R0 Resection	75.8 percentage of participants Interval 61.1 to 90.4

SECONDARY outcome

Timeframe: Up to 3 years

Disease free survival is defined as the time from on study date to evidence of tumor recurrence or death from any cause. Patients who remained alive and disease free were censored at their date of last disease evaluation.

Outcome measures

Outcome measures
Measure	FOLFIRINOX n=43 Participants FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Disease Free Survival	8.6 months Interval 5.1 to 13.4

SECONDARY outcome

Timeframe: Up to 4 years

Overall survival was defined as the time from on study date to death due to any cause. Patients who remained alive were censored at their last known alive date. The Kaplan-Meier method was used to determine the median and 95% confidence interval.

Outcome measures

Outcome measures
Measure	FOLFIRINOX n=43 Participants FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Overall Survival	15.7 months Interval 9.1 to 21.7

SECONDARY outcome

Timeframe: Up to 4 months

Population: Patients who received four treatments of FOLFIRINOX and had at least one post-baseline assessment.

Outcome measures

Outcome measures
Measure	FOLFIRINOX n=34 Participants FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Objective Response Rate (Percentage of Patients With Complete Response or Partial Response)	17.7 percentage of participants Interval 4.8 to 30.5

SECONDARY outcome

Timeframe: Up to 4 months

Population: Patients who received four treatments of FOLFIRINOX and had at least one post-baseline assessment.

Measured by RECIST v1.1 Complete response: Disappearance of all target lesions Partial response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter Stable disease: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started The percentage of patients with objective response and its 95% confidence interval will be provided.

Outcome measures

Outcome measures
Measure	FOLFIRINOX n=34 Participants FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Disease Control Rate (Percentage of Patients With Complete Response, Partial Response, or Stable Disease)	88.2 percentage of participants Interval 77.4 to 99.1

Adverse Events

FOLFIRINOX

Serious events: 15 serious events

Other events: 42 other events

Deaths: 35 deaths

Serious adverse events

Serious adverse events
Measure	FOLFIRINOX n=48 participants at risk FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Blood and lymphatic system disorders Febrile neutropenia	4.2% 2/48 • Number of events 2 • Up to 6 months
Cardiac disorders Cardiac disorders - Other, specify	2.1% 1/48 • Number of events 1 • Up to 6 months
Cardiac disorders Pericardial effusion	2.1% 1/48 • Number of events 1 • Up to 6 months
Gastrointestinal disorders Abdominal pain	2.1% 1/48 • Number of events 1 • Up to 6 months
Gastrointestinal disorders Diarrhea	6.2% 3/48 • Number of events 4 • Up to 6 months
Gastrointestinal disorders Mucositis oral	2.1% 1/48 • Number of events 1 • Up to 6 months
Gastrointestinal disorders Nausea	6.2% 3/48 • Number of events 5 • Up to 6 months
Gastrointestinal disorders Pancreatitis	2.1% 1/48 • Number of events 1 • Up to 6 months
Gastrointestinal disorders Vomiting	6.2% 3/48 • Number of events 6 • Up to 6 months
General disorders Death NOS	4.2% 2/48 • Number of events 2 • Up to 6 months
General disorders Fever	6.2% 3/48 • Number of events 4 • Up to 6 months
Infections and infestations Sepsis	2.1% 1/48 • Number of events 1 • Up to 6 months
Investigations Blood bilirubin increased	2.1% 1/48 • Number of events 1 • Up to 6 months
Investigations Neutrophil count decreased	2.1% 1/48 • Number of events 1 • Up to 6 months
Metabolism and nutrition disorders Acidosis	2.1% 1/48 • Number of events 1 • Up to 6 months
Metabolism and nutrition disorders Dehydration	2.1% 1/48 • Number of events 1 • Up to 6 months
Metabolism and nutrition disorders Hypoglycemia	2.1% 1/48 • Number of events 1 • Up to 6 months
Nervous system disorders Syncope	2.1% 1/48 • Number of events 1 • Up to 6 months
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.1% 1/48 • Number of events 1 • Up to 6 months
Vascular disorders Hypotension	2.1% 1/48 • Number of events 1 • Up to 6 months
Vascular disorders Thromboembolic event	2.1% 1/48 • Number of events 1 • Up to 6 months

Other adverse events

Other adverse events
Measure	FOLFIRINOX n=48 participants at risk FOLFIRINOX consists of the following combination of drugs: 1. Oxaliplatin, 85 mg/m2, IV over 2 hours prior to irinotecan, administered on days 1 and 15 of each 28 day cycle 2. Leucovorin, 400 mg/m2, IV over 2 hours with irinotecan, administered on days 1 and 15 of each 28 day cycle 3. 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.
Gastrointestinal disorders Abdominal pain	6.2% 3/48 • Number of events 4 • Up to 6 months
Gastrointestinal disorders Bloating	6.2% 3/48 • Number of events 4 • Up to 6 months
Gastrointestinal disorders Constipation	8.3% 4/48 • Number of events 4 • Up to 6 months
Gastrointestinal disorders Diarrhea	47.9% 23/48 • Number of events 35 • Up to 6 months
Gastrointestinal disorders Mucositis oral	10.4% 5/48 • Number of events 6 • Up to 6 months
Gastrointestinal disorders Nausea	43.8% 21/48 • Number of events 29 • Up to 6 months
Gastrointestinal disorders Vomiting	20.8% 10/48 • Number of events 11 • Up to 6 months
General disorders Fatigue	60.4% 29/48 • Number of events 41 • Up to 6 months
General disorders Fever	6.2% 3/48 • Number of events 3 • Up to 6 months
Metabolism and nutrition disorders Anorexia	20.8% 10/48 • Number of events 11 • Up to 6 months
Metabolism and nutrition disorders Hypokalemia	18.8% 9/48 • Number of events 10 • Up to 6 months
Nervous system disorders Dysgeusia	6.2% 3/48 • Number of events 3 • Up to 6 months
Nervous system disorders Peripheral sensory neuropathy	33.3% 16/48 • Number of events 26 • Up to 6 months

Additional Information

Dr. Amikar Sehdev

IndianaU

Phone: (317) 274-0339

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place