This is a phase II, single-arm, open-label, clinical study to investigate the efficacy and tolerability of a combination of liposomal irinotecan (nal-IRI) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-nal-IRI) for treatment of patients with locally advanced pancreatic carcinoma (LAPC).
This is a phase II, single-arm, open-label, clinical study to investigate the efficacy and tolerability of a combination of liposomal irinotecan (nal-IRI) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-nal-IRI) for treatment of patients with locally advanced pancreatic carcinoma (LAPC). Each subject will be screened for eligibility by evaluation including medical history, physical examination, performance status, blood tests, computed tomographic (CT) scans, and electrocardiogram. Within 28 days of screening, the consented subjects will have a central venous access device placed and then start treatment. For every 2-week cycle of FOLFOX-nal-IRI, each subject will receive nal-IRI (irinotecan free base 50 mg/m2 intravenously over 90 minutes), oxaliplatin (60 mg/m2 intravenously over 2 hours), leucovorin (400 mg/m2 intravenously over 2 hours), and 5-fluorouracil 2,400 mg/m2 intravenously over 46 hours). Tumor response/surgical assessment will be evaluated after every 4 cycles of treatment with CT scans using RECIST 1.1 criteria. If the tumor becomes surgically resectable and the subject is a surgical candidate as determined by a multidisciplinary team, the subject will undergo surgery (at which point he/she would enter survival follow-up). If the tumor remains unresectable and there is no tumor progression, each subject will be treated up to a total of 12 cycles of FOLFOX-nal-IRI. Following treatment with 12 cycles of FOLFOX-nal-IRI, if tumor remains unresectable, the subjects may receive further treatment (chemotherapy using the same regimen or of the treating physician's choice, or chemoradiation therapy) or observation as determined by the physician. During the course of treatment, if the subjects develop unacceptable toxicity and/or disease progression, the treatment will be discontinued, and the subjects will be further managed at the discretion of the treating oncologists.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
FOLFOX (Oxaliplatin, Leucovorin, 5-Fluorouracil)
Liposomal Irinotecan
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, United States
Rutgers Cancer Institute of new Jersey
New Brunswick, New Jersey, United States
Penn State Cancer Institute
Hershey, Pennsylvania, United States
Disease Control Rate (DCR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Disease Control Rate (DCR) = CR +PR+SD
Time frame: Up to 22 months
Objective Response Rate (ORR) at 8 Weeks
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Overall Response (OR) = CR + PR.
Time frame: 8 weeks
Objective Response Rate (ORR) at 16 Weeks
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Overall Response (OR) = CR + PR.
Time frame: 16 weeks
Objective Response Rate (ORR) at 24 Weeks
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Overall Response (OR) = CR + PR.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 24 weeks
Stable Disease Rate (SDR) at 8 Weeks
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Stable disease rate (SDR) is determined by the proportion of subjects with no progression of disease as defined by RECIST 1.1, at 8 weeks following initiation of FOLFOX-nal-IRI.
Time frame: 8 Weeks
Stable Disease Rate (SDR) at 16 Weeks
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Stable disease rate (SDR) as determined by the proportion of subjects with no progression of disease as defined by RECIST 1.1, at 16 weeks following initiation of FOLFOX-nal-IRI.
Time frame: 16 Weeks
Stable Disease Rate (SDR) at 24 Weeks
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Stable disease rate (SDR) as determined by the proportion of subjects with no progression of disease as defined by RECIST 1.1, at 24 weeks following initiation of FOLFOX-nal-IRI.
Time frame: 24 Weeks
Proportion of Subjects Able to Undergo Surgical Resection
Rate of resectability as determined by the proportion of subjects who undergo surgical resection of tumors.
Time frame: 12 months
Response of Serum CA19-9 Levels
A CA 19-9 test measures the amount of a protein called CA19-9 (cancer antigen 19-9) in a sample of blood. Healthy people can have small amounts of CA 19-9 in their blood. High levels of CA 19-9 are often a sign of pancreatic cancer. Increasing CA 19-9 levels mean the tumor is growing, whether decreasing CA 19-9 levels may mean the tumor is shrinking. The Mean of the percentage change from baseline in serum CA19-9 levels associated with best confirmed response (PR, SD, PD) per RECIST 1.1 are reported in the outcome measure data table.
Time frame: Up to 7 months
Progression-Free Survival (PFS)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Progression-free survival (PFS) as determined by the time interval from the date of first dose of study drug to first documented disease progression or death from any cause, whichever occurs first.
Time frame: Up to 22 months
Overall Survival (OS)
Overall survival (OS) is defined as time from the first dose of study drug to date of death from any cause.
Time frame: Up to 31 months
Number of Participants With Adverse Events
Adverse events will be assessed to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Time frame: Up to 7 months
Quality of Life (QoL) Assessment: Global Health Status (EORTC QLQ-C30)
This secondary outcome measure evaluates overall quality of life using the Global Health Status scale from the EORTC QLQ-C30. Scores range from 0 to 100, with higher scores indicating better global health and quality of life. Mean (SD) scores are reported by assessment period, including only those participants who reached the defined time points (e.g., Cycle 9).
Time frame: Treatment Cycle 1 (14 days), Treatment Cycle 5 (70 days), Treatment Cycle 9 (126 days), Follow-Up (7 Months)