- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03861702
Liposomal Irinotecan in Combination With Oxaliplatin, Leucovorin, and 5-fluorouracil for Patients With Locally Advanced Pancreatic Carcinoma:
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Nelson Yee, MD
- Phone Number: 280677 717-531-0003
- Email: nyee@hmc.psu.edu
Study Contact Backup
- Name: Rae Richards
- Phone Number: 38 317-634-5842
- Email: rrichards@hoosiercancer.org
Study Locations
-
-
Illinois
-
Chicago, Illinois, United States, 60611
- Northwestern University Feinberg School of Medicine
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Indiana University Melvin and Bren Simon Comprehensive Cancer Center
-
-
New Jersey
-
New Brunswick, New Jersey, United States, 08903
- Rutgers Cancer Institute of New Jersey
-
-
Pennsylvania
-
Hershey, Pennsylvania, United States, 17033
- Penn State Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
- Platelet (Plt): >/=100,000/uL
Renal
- Serum creatinine: </=1.5 x upper limit of normal (ULN) OR
- Calculated creatinine clearance using the Cockcroft-Gualt formula: >/=50 mL/min for subjects with creatinine levels >1.5 ULN
Hepatic
- Total bilirubin: </=1.5 x ULN (biliary drainage is allowed for biliary obstruction). Patients with Gilbert's syndrome with a total bilirubin </=3.0 x ULN and direct bilirubin within normal limits are permitted
- Aspartate aminotransferase (AST): </=2.5 x ULN
- Alanine aminotransferase (ALT): </=2.5 x ULN
- Albumin: >/=3.0 g/dL
- Coagulation ---International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT): </=1.5 x ULN unless subject is receiving anticoagulant therapy, as long as PT, INR or PTT is within therapeutic range of intended use of anticoagulants
- 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 9 months (females) or 6 months (males) 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.
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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
FOLFOX (Oxaliplatin, Leucovorin, 5-Fluorouracil)
Liposomal Irinotecan
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Control Rate (DCR)
Time Frame: 24 weeks
|
Disease Control Rate (DCR) as determined by the proportion of subjects with complete response, partial response, or stable disease, as defined by RECIST 1.1 at 24 weeks for nal-IRI in combination with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-nal-IRI), in subjects with locally advanced pancreatic carcinoma (for the subjects whose tumors remain unresectable following 12 cycles of FOLFOX-nal-IRI).
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR) at 8 Weeks
Time Frame: 8 weeks
|
Objective response rate (ORR) as determined by the proportion of subjects with either complete response or partial response, as defined by RECIST 1.1, at 8 weeks following initiation of FOLFOX-nal-IRI.
|
8 weeks
|
Objective Response Rate (ORR) at 16 Weeks
Time Frame: 16 weeks
|
Objective response rate (ORR) as determined by the proportion of subjects with either complete response or partial response, as defined by RECIST 1.1, at 16 weeks following initiation of FOLFOX-nal-IRI.
|
16 weeks
|
Objective Response Rate (ORR) at 24 Weeks
Time Frame: 24 weeks
|
Objective response rate (ORR) as determined by the proportion of subjects with either complete response or partial response, as defined by RECIST 1.1, at 24 weeks following initiation of FOLFOX-nal-IRI.
|
24 weeks
|
Stable Disease Rate (SDR) at 8 Weeks
Time Frame: 8 Weeks
|
Stable disease rate (SDR) as 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.
|
8 Weeks
|
Stable Disease Rate (SDR) at 16 Weeks
Time Frame: 16 Weeks
|
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.
|
16 Weeks
|
Stable Disease Rate (SDR) at 24 Weeks
Time Frame: 24 Weeks
|
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.
|
24 Weeks
|
Proportion of Subjects able to undergo surgical resection
Time Frame: 6 months
|
Rate of resectability as determined by the proportion of subjects who undergo surgical resection of tumors.
|
6 months
|
Response of serum CA19-9 levels
Time Frame: Every 4 weeks, up to 6 months
|
The serum levels of CA19-9 prior to initiation of chemotherapy and after every 2 cycles (every 4 weeks) following initiation of FOLFOX-nal-IRI.
|
Every 4 weeks, up to 6 months
|
Progression-Free Survival (PFS)
Time Frame: 18 months
|
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, if evaluable.
|
18 months
|
Overall Survival (OS)
Time Frame: 18 months
|
Overall survival (OS) as defined as the time interval from the date of the first dose of study drug to date of death from any cause.
|
18 months
|
Adverse Events
Time Frame: 6 months
|
Describe safety and tolerability of (FOLFOX-nal-IRI) by reporting Grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.
|
6 months
|
Quality of Life Assessment
Time Frame: 6 months
|
Quality of life as measured at baseline and after every 4 cycles (every 8 weeks) using the European Organization for Research and Treatment of Cancer Quality-of-Life Core Questionnaire (EORTC-QLQ-C30).
|
6 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Nelson Yee, Penn State Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Carcinoma
- Pancreatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Irinotecan
Other Study ID Numbers
- BTCRC-GI15-067
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Locally Advanced Pancreatic Carcinoma(LAPC)
-
Amsterdam UMC, location VUmcCompletedPancreatic Cancer | Locally Advanced Pancreatic Carcinoma (LAPC) | Non-metastasized Unresectable Pancreatic CarcinomaNetherlands
-
Washington University School of MedicineNational Cancer Institute (NCI)RecruitingCervical Cancer | Pancreatic Cancer | Pancreas Cancer | Locally Advanced Cervical Carcinoma | Locally Advanced Cervical Cancer | Cancer of the Pancreas | Locally Advanced Pancreatic Carcinoma | Locally Advanced Pancreatic Cancer | Cancer of the Cervix | Locally Advanced Pancreas CancerUnited States
-
TriSalus Life Sciences, Inc.RecruitingLocally Advanced Pancreatic AdenocarcinomaUnited States
-
Fuda Cancer Hospital, GuangzhouCompletedLocally Advanced Pancreatic AdenocarcinomaChina
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingMetastatic Bladder Urothelial Carcinoma | Metastatic Renal Pelvis Urothelial Carcinoma | Metastatic Ureter Urothelial Carcinoma | Metastatic Urethral Urothelial Carcinoma | Metastatic Urothelial Carcinoma | Locally Advanced Bladder Urothelial Carcinoma | Locally Advanced Renal Pelvis Urothelial... and other conditionsUnited States
-
Jonsson Comprehensive Cancer CenterArcus Biosciences, Inc.SuspendedBorderline Resectable Pancreatic Adenocarcinoma | Locally Advanced Pancreatic Ductal AdenocarcinomaUnited States
-
Georgetown UniversityERYtech PharmaActive, not recruitingMetastatic Pancreatic Ductal Adenocarcinoma | Locally Advanced Pancreatic Ductal AdenocarcinomaUnited States
-
Impact Biotech LtdImpact biotech Ltd.Not yet recruitingLocally Advanced Unresectable Pancreatic Adenocarcinoma
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)RecruitingPancreas Adenocarcinoma | Locally Advanced Pancreatic Adenocarcinoma | Borderline Resectable Pancreatic AdenocarcinomaUnited States
-
Roswell Park Cancer InstituteIpsenActive, not recruitingUnresectable Pancreatic Neuroendocrine Carcinoma | Locally Advanced Digestive System Neuroendocrine Carcinoma | Locally Advanced Pancreatic Neuroendocrine Carcinoma | Metastatic Digestive System Neuroendocrine Carcinoma | Metastatic Pancreatic Neuroendocrine Carcinoma | Refractory Digestive... and other conditionsUnited States
Clinical Trials on FOLFOX regimen
-
Fox Chase Cancer CenterSuspended
-
Biotheus Inc.RecruitingHepatocellular CarcinomaChina
-
Tang-Du HospitalRecruiting
-
Jiangsu Province Hospital of Traditional Chinese...UnknownPeripheral NeuropathyChina
-
Ohio State UniversityOsato Research InstituteCompleted
-
Sixth Affiliated Hospital, Sun Yat-sen UniversityRecruitingColorectal Cancer | Chemotherapy Effect | Liver Metastases | Circulating Tumor CellChina
-
AmgenCompleted
-
Stanford UniversityActive, not recruitingRectal CancerUnited States
-
Federation Francophone de Cancerologie DigestiveRoche Pharma AGCompleted
-
WntResearch ABInstitut Català d'Oncologia; SMS-Oncology BV; SAGA diagnostics AB; Unilabs A/S; BioVica...Active, not recruiting