Liposomal Irinotecan in Combination With Oxaliplatin, Leucovorin, and 5-fluorouracil for Patients With Locally Advanced Pancreatic Carcinoma:
- 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 protocol, All screening labs to be obtained within 14 days prior to initiation of study treatment.
- Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days of study registration and within 72 hours of Cycle 1 Day 1. NOTE: Female subjects are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- Female subjects of childbearing potential and males must be willing to abstain from behaviors that could lead to pregnancy (heterosexual activity, sperm donation, in vitro fertilization, etc.) or to use 2 forms of effective methods of contraception from the time of informed consent until 180 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. The subject should be able to understand the purpose and risks of the study and provide a signed and dated informed consent form.
- 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.
- 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.
- Treatment with any investigational drug within 30 days prior to registration, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing of this study.
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 will be evaluated 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.
Trial Phase Phase II
Trial Type Treatment
- Primary ID BTCRC-GI15-067
- Secondary IDs NCI-2020-05944
- Clinicaltrials.gov ID NCT03861702