A Phase II Study to Evaluate the Efficacy of Liposomal Irinotecan in Combination With Oxaliplatin, Leucovorin, and 5-fluorouracil for Patients With Locally Advanced Pancreatic Carcinoma: Big Ten Cancer Research Consortium BTCRC-GI15-067
Overview
- Phase
- Phase 2
- Intervention
- FOLFOX regimen
- Conditions
- Locally Advanced Pancreatic Carcinoma(LAPC)
- Sponsor
- Nelson Yee
- Enrollment
- 28
- Locations
- 4
- Primary Endpoint
- Disease Control Rate (DCR)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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).
Detailed Description
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.
Investigators
Nelson Yee
Sponsor-Investigator
Big Ten Cancer Research Consortium
Eligibility Criteria
Inclusion Criteria
- •Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Age ≥ 18 years at the time of consent.
- •ECOG Performance Status of 0-1 within 28 days prior to registration.
- •Histological or cytological confirmation of pancreatic carcinoma.
- •Measurable disease according to RECIST v1.1 within 28 days prior to registration.
- •Previously untreated pancreatic carcinoma considered as locally advanced unresectable according to NCCN guidelines.
- •Demonstrate adequate organ function as defined in the table below; All screening labs to be obtained within 14 days prior to initiation of study treatment.
- •Hematological
- •Absolute Neutrophil Count (ANC): \>/=1500/uL
- •Hemoglobin (Hgb): \>/=8 g/dL with blood transfusion permitted
Exclusion Criteria
- •Known hypersensitivity to irinotecan liposome, other liposomal products, oxaliplatin, 5-fluorouracil, leucovorin, or any ingredients in those preparations.
- •Pre-existing peripheral neuropathy (Grade 3 or 4) during screening.
- •Major surgery within 4 weeks of starting treatment.
- •Active uncontrolled cardiac arrhythmia or congestive heart failure (class 3 or 4 as defined by the New York Heart Association Functional Classification); or history of myocardial infarction, unstable angina; or acute coronary syndrome within 6 months prior to enrollment.
- •Known history of human immunodeficiency virus (HIV), or hepatic cirrhosis caused by active infection with hepatitis B virus (HBV, as defined by HBsAg positivity or positive DNA). Testing is not required for study entry if there is no clinical suspicion. Note: hepatic cirrhosis caused by other factors (ex. alcoholic cirrhosis) may be considered on a case-by-case basis if, in the opinion of the treating investigator, the disease is unlikely to compromise the subject's safety or put the study outcomes at unnecessary risk.
- •Any medical condition, life-threatening illness, or organ dysfunction, which in the investigator's opinion, can compromise the subject's safety or put the study outcomes at unnecessary risk.
- •Uncontrolled active systemic infection.
- •Concomitant medications that are prohibited in this study and they cannot be switched to alternative medications.
- •Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- •Known additional malignancy that is active and/or progressive requiring treatment within 2 years of screening for this study; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, low-grade prostate cancer, or other cancer for which the subject has been disease-free for at least five years. Additional exceptions could be considered if agreed by sponsor-investigator and site investigator assuming the disease is considered extremely unlikely to confound evaluation of disease status.
Arms & Interventions
FOLFOX + Irinotecan
Oxaliplatin 60 mg/m2 Intravenously (IV) over 2 hours Liposomal Irinotecan (free base) 50 mg/m2 IV over 90 minutes after completion of oxaliplatin Leucovorin 400 mg/m2 IV over 30 minutes after completion of liposomal irinotecan 5-Fluorouracil 2,400 mg/m2 IV over 46 hours via infusion pump at home All drugs administered on day 1 of each 14 day cycle.
Intervention: FOLFOX regimen
FOLFOX + Irinotecan
Oxaliplatin 60 mg/m2 Intravenously (IV) over 2 hours Liposomal Irinotecan (free base) 50 mg/m2 IV over 90 minutes after completion of oxaliplatin Leucovorin 400 mg/m2 IV over 30 minutes after completion of liposomal irinotecan 5-Fluorouracil 2,400 mg/m2 IV over 46 hours via infusion pump at home All drugs administered on day 1 of each 14 day cycle.
Intervention: Liposomal Irinotecan
Outcomes
Primary Outcomes
Disease Control Rate (DCR)
Time Frame: Up to 22 months
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
Secondary Outcomes
- Objective Response Rate (ORR) at 24 Weeks(24 weeks)
- Stable Disease Rate (SDR) at 8 Weeks(8 Weeks)
- Stable Disease Rate (SDR) at 16 Weeks(16 Weeks)
- Stable Disease Rate (SDR) at 24 Weeks(24 Weeks)
- Proportion of Subjects Able to Undergo Surgical Resection(12 months)
- Response of Serum CA19-9 Levels(Up to 7 months)
- Progression-Free Survival (PFS)(Up to 22 months)
- Overall Survival (OS)(Up to 31 months)
- Number of Participants With Adverse Events(Up to 7 months)
- Quality of Life (QoL) Assessment: Global Health Status (EORTC QLQ-C30)(Treatment Cycle 1 (14 days), Treatment Cycle 5 (70 days), Treatment Cycle 9 (126 days), Follow-Up (7 Months))
- Objective Response Rate (ORR) at 8 Weeks(8 weeks)
- Objective Response Rate (ORR) at 16 Weeks(16 weeks)