Pancreatic Adenocarcinoma
Conditions
Keywords
pancreatic adenocarcinoma, neoadjuvant, ONIVYDE, chemotherapy, borderline resectable, resectable
Brief summary
This is a phase II, single arm, non-randomized, open label study of liposomal irinotecan with FOLFOX in the neoadjuvant setting in patients with resectable or borderline resectable, previously untreated pancreatic adenocarcinoma. The primary objective of this study is to investigate the safety and feasibility of this treatment regimen in this patient population.
Interventions
DRUGLiposomal Irinotecan
Subjects will receive 60 mg/m2 intravenously on Day 1 of each 14 day cycle.
DRUGFOLFOX regimen
Subjects will receive FOLFOX (oxaliplatin 60 mg/m2 IV, leucovorin 400 mg/m2 IV, and 5-fluorouracil 2400 mg/m2 IV) on Day 1 of each 14 day cycle.
Sponsors
University of Florida
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Must be at least 18 years of age. * A new clinical diagnosis of resectable or borderline resectable, previously untreated pancreatic adenocarcinoma confirmed by pathologic specimen evaluation * No clinical evidence of metastatic disease * Potentially resectable local disease, as confirmed by CT or MRI of the abdomen * ECOG performance status of 0 or 1 * Any biliary obstruction must have been treated. * Subjects with known or suspected Gilbert's disease must be formally tested for UGT1A1\*28 with results available to study team prior to treatment initiation * Adequate organ function; as defined by: i. Hematologic- 1. ANC \> 1,500 cells/μl without the use of hematopoietic growth factors; and 2. Platelet count \> 100,000 cells/μl; and 3. Hemoglobin \> 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL) ii. Hepatic- <!-- --> 1. Serum total bilirubin within 1.5 x upper limit of normal (ULN) for the institution, with a trend downwards (biliary drainage is allowed for biliary obstruction), 2. AST and ALT less than or equal to 2.5 x ULN iii. Renal- Serum creatinine less than or equal to 1.5 x ULN iv. Cardiac- Normal ECG or ECG without any clinically significant findings as defined by the treating physician * Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 7 months after the last dose of study drug to minimize the risk of pregnancy * Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 4 months following the last dose of study drug.
Exclusion criteria
* A medical history of prior anti-cancer treatment for pancreatic cancer. * Locally advanced unresectable disease or evidence of metastatic disease. * Any other invasive malignancy within the past three years. * Presence of any known contraindications to or hypersensitivities to the investigational products. * Use of strong CYP3A4 inhibitors or inducers which cannot be discontinued prior to study entry. * A non-surgical candidate. * Subject is unable to understand, provide consent or comply with study requirements, treatments or instructions in the opinion of the treating physician. * Uncontrolled diarrhea, active infection, known interstitial lung disease or other medical condition that precludes safe administration of this combination therapy consistent with manufacturer recommendations. * Unwilling/unable to comply with birth control requirements while on study. * Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 7 months for females and 4 months for males after the last dose of study drug. * Females who are pregnant or breastfeeding. * History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician. * Prisoners or subjects who are involuntarily incarcerated. * Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness. * Subjects demonstrating an inability to comply with the study and/or follow-up procedures. * Known dihydrypyrimidine (DPD) deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Had Post-operative Complications 30 Days Post-surgery | 30 days | To determine the percentage of subjects who had post-operative complications 30 days post-surgery. Post-operative complications considered for this outcome measure included hospital readmission, death, second surgery or interventional procedure, or major complications extending hospital stay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Completed All Intended Cycles of Treatment | 4 months | To determine the percentage of subjects that completed all eight intended cycles of treatment with liposomal irinotecan with FOLFOX. |
| Percentage of Subjects Who Achieved a Complete Surgical Resection (R0) | 7 months | To determine the percentage of subjects who achieved a complete surgical resection (R0),which is determined from review of pathology reports and inclusive of pathologic nodal status and TNM staging. A complete surgical resection (R0) has been achieved when surgical margins are microscopically negative for residual tumor. |
| Percentage of Patients Achieving a Best Overall Response of Partial or Complete Response (Objective Response Rate) | 5 months | To determine the percentage of patients achieving a best overall response of partial or complete response according to RECIST 1.1 criteria from the start of the treatment until disease progression/recurrence. Per RECIST 1.1 criteria, a complete response is the disappearance of all target lesions (any pathological lymph nodes \[whether target or non-target\] must have reduction in short axis to \<10 mm). A partial response is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. |
| Difference Between Baseline and Maximal Nadir of Serum CA19-9 Level | 9 months | To determine the difference between baseline and maximal nadir of serum CA19-9 level |
| Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Cycles 1, 5, and 8 and at pre-surgical evaluation and post-surgical follow-up visits | To determine subject physical, social, emotional, and functional well-being during treatment, as measured by the FACT-G questionnaire. The FACT-G is a 27 item questionnaire where subjects respond to item with a score of 0-4. The responses to the questions are summed to calculate 4 sub-scores: physical well-being (score range 0-28), social well-being (score range: 0-28), emotional well-being (score range: 0-24), and functional well-being (score range: 0-28). The 4 sub-scores are also summed to calculate the total score. Total scores range from 0-108. A higher sub-score or total score indicates better quality of life. Participants completed the FACT-G at Cycles 1, 5, and 8, as well as at the pre-surgical evaluation and follow-up visits. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORThomas George, MD
University of Florida
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Liposomal Irinotecan With FOLFOX Subjects will receive 8 cycles and each cycle is 14 days.
Liposomal Irinotecan: Subjects will receive 60 mg/m2 intravenously on Day 1 of each 14 day cycle.
FOLFOX regimen: Subjects will receive FOLFOX (oxaliplatin 60 mg/m2 IV, leucovorin 400 mg/m2 IV, and 5-fluorouracil 2400 mg/m2 IV) on Day 1 of each 14 day cycle. | 45 |
| Total | 45 |
Baseline characteristics
| Characteristic | Liposomal Irinotecan With FOLFOX |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 21 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 63.133 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 27 / 45 |
| other Total, other adverse events | 45 / 45 |
| serious Total, serious adverse events | 20 / 45 |
Outcome results
Primary
Percentage of Subjects Who Had Post-operative Complications 30 Days Post-surgery
To determine the percentage of subjects who had post-operative complications 30 days post-surgery. Post-operative complications considered for this outcome measure included hospital readmission, death, second surgery or interventional procedure, or major complications extending hospital stay.
Time frame: 30 days
Population: The analyzed population for this outcome measure only include those participants who had surgery after completing study treatment with liposomal irinotecan with FOLFOX.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liposomal Irinotecan With FOLFOX | Percentage of Subjects Who Had Post-operative Complications 30 Days Post-surgery | 10.3 percentage of participants |
Secondary
Difference Between Baseline and Maximal Nadir of Serum CA19-9 Level
To determine the difference between baseline and maximal nadir of serum CA19-9 level
Time frame: 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Irinotecan With FOLFOX | Difference Between Baseline and Maximal Nadir of Serum CA19-9 Level | 756.9 units/mL | Standard Deviation 2932.7 |
Secondary
Percentage of Patients Achieving a Best Overall Response of Partial or Complete Response (Objective Response Rate)
To determine the percentage of patients achieving a best overall response of partial or complete response according to RECIST 1.1 criteria from the start of the treatment until disease progression/recurrence. Per RECIST 1.1 criteria, a complete response is the disappearance of all target lesions (any pathological lymph nodes \[whether target or non-target\] must have reduction in short axis to \<10 mm). A partial response is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.
Time frame: 5 months
Population: The analyzed population for this outcome measure only includes those participants who were evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liposomal Irinotecan With FOLFOX | Percentage of Patients Achieving a Best Overall Response of Partial or Complete Response (Objective Response Rate) | 44.7 percentage of participants |
Secondary
Percentage of Subjects Who Achieved a Complete Surgical Resection (R0)
To determine the percentage of subjects who achieved a complete surgical resection (R0),which is determined from review of pathology reports and inclusive of pathologic nodal status and TNM staging. A complete surgical resection (R0) has been achieved when surgical margins are microscopically negative for residual tumor.
Time frame: 7 months
Population: The analyzed population for this outcome measure only includes those subjects who had surgery after completion of treatment with liposomal irinotecan with FOLFOX.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liposomal Irinotecan With FOLFOX | Percentage of Subjects Who Achieved a Complete Surgical Resection (R0) | 89.7 percentage of participants |
Secondary
Percentage of Subjects Who Completed All Intended Cycles of Treatment
To determine the percentage of subjects that completed all eight intended cycles of treatment with liposomal irinotecan with FOLFOX.
Time frame: 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liposomal Irinotecan With FOLFOX | Percentage of Subjects Who Completed All Intended Cycles of Treatment | 73.3 percentage of participants |
Secondary
Subject Physical, Social, Emotional, and Functional Well-being During Treatment
To determine subject physical, social, emotional, and functional well-being during treatment, as measured by the FACT-G questionnaire. The FACT-G is a 27 item questionnaire where subjects respond to item with a score of 0-4. The responses to the questions are summed to calculate 4 sub-scores: physical well-being (score range 0-28), social well-being (score range: 0-28), emotional well-being (score range: 0-24), and functional well-being (score range: 0-28). The 4 sub-scores are also summed to calculate the total score. Total scores range from 0-108. A higher sub-score or total score indicates better quality of life. Participants completed the FACT-G at Cycles 1, 5, and 8, as well as at the pre-surgical evaluation and follow-up visits.
Time frame: Cycles 1, 5, and 8 and at pre-surgical evaluation and post-surgical follow-up visits
Population: The number of participants analyzed for some sub-scores and total scores differs from the overall number of participants due to missing questionnaire responses for some participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Physical well-being (Cycle 1) | 5.1 score on a scale | Standard Deviation 4.8 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Social well-being (Cycle 1) | 24.7 score on a scale | Standard Deviation 4 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Emotional well-being (Cycle 1) | 8.7 score on a scale | Standard Deviation 4.3 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Functional well-being (Cycle 1) | 19.8 score on a scale | Standard Deviation 5 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Total score (Cycle 1) | 58.4 score on a scale | Standard Deviation 6.6 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Physical well-being (Cycle 5) | 8.4 score on a scale | Standard Deviation 4.8 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Social well-being (Cycle 5) | 24.2 score on a scale | Standard Deviation 4.2 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Emotional well-being (Cycle 5) | 7.4 score on a scale | Standard Deviation 4.6 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Functional well-being (Cycle 5) | 18.5 score on a scale | Standard Deviation 5.9 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Total score (Cycle 5) | 58.5 score on a scale | Standard Deviation 9.9 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Physical well-being (Cycle 8) | 8.1 score on a scale | Standard Deviation 4.9 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Social well-being (Cycle 8) | 24.5 score on a scale | Standard Deviation 3.9 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Emotional well-being (Cycle 8) | 8.3 score on a scale | Standard Deviation 4.3 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Functional well-being (Cycle 8) | 18.3 score on a scale | Standard Deviation 5.2 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Total score (Cycle 8) | 59.2 score on a scale | Standard Deviation 8.3 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Physical well-being (Pre-surgical evaluation) | 5.9 score on a scale | Standard Deviation 4.4 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Social well-being (Pre-surgical evaluation) | 24.5 score on a scale | Standard Deviation 3.7 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Emotional well-being (Pre-surgical evaluation) | 8.1 score on a scale | Standard Deviation 4 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Functional well-being (Pre-surgical evaluation) | 19.1 score on a scale | Standard Deviation 5.7 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Total score (Pre-surgical evaluation) | 57.6 score on a scale | Standard Deviation 8.1 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Physical well-being (Follow-up) | 8.5 score on a scale | Standard Deviation 5.5 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Social well-being (Follow-up) | 24.6 score on a scale | Standard Deviation 3.8 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Emotional well-being (Follow-up) | 7.8 score on a scale | Standard Deviation 4 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Functional well-being (Follow-up) | 15.4 score on a scale | Standard Deviation 5.9 |
| Liposomal Irinotecan With FOLFOX | Subject Physical, Social, Emotional, and Functional Well-being During Treatment | Total score (Follow-up) | 56.4 score on a scale | Standard Deviation 8.1 |