TAS102 In Combination With NAL-IRI In Advanced GI Cancers

Study Overview

TAS102 in Combination With NAL-IRI in Advanced GI Cancers

This phase I/II trial studies the best dose and how well trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) and nanoliposomal irinotecan work in treating patients with gastrointestinal cancers that have spread to other places in the body (metastatic) or cannot be removed by surgery. Drugs used in the chemotherapy, such as trifluridine/tipiracil hydrochloride combination agent TAS-102 and nanoliposomal irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

PRIMARY OBJECTIVES: I. Determine the recommended phase II dose for the combination of TAS-102 and nanoliposomal irinotecan (nanoliposomal [nal]-IRI). (Phase I) II. Evaluate the activity of the combination of TAS102 and nal-IRI in previously treated patients with metastatic colorectal cancer and pancreatic cancer. (Phase II) SECONDARY OBJECTIVES: I. Define the toxicity profile of the combination of TAS-102 and nal-IRI. II. Evaluate the response duration, progression free, and overall survival of the combination of TAS-102 and nal-IRI in previously treated patients with metastatic colorectal cancer and pancreatic cancer. OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive nanoliposomal irinotecan intravenously (IV) over 90 minutes on day 1 and trifluridine/tipiracil hydrochloride combination agent TAS-102 orally (PO) twice daily (BID) on days 1-5. Cycles repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then every 8 or 12 weeks thereafter.

Colorectal Adenocarcinoma
Gastric Adenocarcinoma
Metastatic Pancreatic Adenocarcinoma
Non-Resectable Cholangiocarcinoma
Stage IV Colorectal Cancer
Stage IV Gastric Cancer
Stage IV Pancreatic Cancer
Stage IVA Colorectal Cancer
Stage IVB Colorectal Cancer
Stage III Colorectal Cancer
Stage III Gastric Cancer
Stage III Pancreatic Cancer
Unresectable Digestive System Adenocarcinoma
Unresectable Pancreatic Carcinoma

DRUG: Nanoliposomal Irinotecan
DRUG: Trifluridine and Tipiracil Hydrochloride

IRB00098958
NCI-2017-01661 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
Winship4146-17 (OTHER Identifier) (OTHER: Emory University Hospital/Winship Cancer Institute)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2017-12-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-01-06
First Submitted that Met QC Criteria 2017-12-06	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-01-07
First Posted (ACTUAL) 2017-12-11	Results First Posted N/A	Last Verified 2025-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (Nal-IRI, TAS-102) Patients receive nanoliposomal irinotecan IV over 90 minutes on day 1 and combination of trifluridine/tipiracil hydrochloride combination agent TAS-102 PO BID on days 1-5. Cycles repeat every 2 weeks in the absence of disease progression or unacceptable t	DRUG: Nanoliposomal Irinotecan Given IV DRUG: Trifluridine and Tipiracil Hydrochloride Given PO

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (Nal-IRI, TAS-102)

Patients receive nanoliposomal irinotecan IV over 90 minutes on day 1 and combination of trifluridine/tipiracil hydrochloride combination agent TAS-102 PO BID on days 1-5. Cycles repeat every 2 weeks in the absence of disease progression or unacceptable t

DRUG: Nanoliposomal Irinotecan

Given IV

DRUG: Trifluridine and Tipiracil Hydrochloride

Given PO

Primary Outcome Measures	Measure Description	Time Frame
Incidence of adverse events of trifluridine/tipiracil hydrochloride combination agent TAS-102 in combination with nanoliposomal irinotecan	Assessed using Common Terminology Criteria for Adverse Events version 4.0.	Up to 3 years after end of treatment
Overall response rate based on modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	Defined as the proportion of patients who achieved a complete response (complete response: disappearance of all target tumors) or a partial response (partial response: ≥ 30% decrease in the sum of the longest diameters of target tumors).	Up to 3 years after end of treatment

Secondary Outcome Measures	Measure Description	Time Frame
Progression free survival	Will be evaluated.	Up to 3 years after end of treatment
Response duration	Will be estimated by Kaplan-Meier method. P values will be two-sided with significance level of .05.	From initial response until documented tumor progression, assessed up to 3 years
Response rate	Response assessment will be done according to RECIST 1.1 criteria. A repeat imaging scan of the same modality and technique will be repeated after 4 weeks for confirmation of response.	Up to 3 years after end of treatment

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Subjects must have histologic or cytological confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1; acquisition of existing formalin fixed paraffin embedded (FFPE) tumor tissue by study investigators is not mandatory for enrollment on the trial; patients without previous histologic/cytologic confirmation must have freshly obtained biopsy for routine pathologic evaluation before enrolment on the study
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, cholangiocarcinoma, pancreatic, colorectal) who have failed at least one prior therapy; subjects must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting
In the dose expansion phase, Arm A will be open for 25 patients with pancreatic adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have not received prior irinotecan; patients must have received at least one prior line of standard treatment for locally advanced or metastatic disease
In dose expansion phase, Arm B will be open for 25 patients with colorectal adenocarcinoma; patients must have histologic diagnosis and metastatic disease and have not received prior irinotecan; patients must have received at least one prior line of standard treatment for locally advanced or metastatic disease
Presence of measurable disease based on RECIST 1.1; subjects with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
Adequate renal function as evidenced by a serum creatinine ≤ 1.5 x upper limit of normal (ULN)
Recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy
Able to understand and sign an informed consent (or have a legal representative who is able to do so)
Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Female subjects of childbearing potential must be willing to use an adequate method of contraception; Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
Male subjects of childbearing potential must agree to use an adequate method of contraception; Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
Absolute neutrophil count (ANC) ≥ 1,500/ul without the use of hematopoietic growth factors (within 14 days of treatment initiation)
Platelets ≥ 100,000/ul (within 14 days of treatment initiation)
Hemoglobin ≥ 8 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 8 g/dL) (within 14 days of treatment initiation)
Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) ≥ 50 mL/min for subject with creatinine levels > 1.5 X institutional ULN (within 14 days of treatment initiation)

Creatinine clearance should be calculated per institutional standard
Serum total bilirubin within normal range for the institution (biliary drainage is allowed for biliary obstruction) (within 14 days of treatment initiation)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases (within 14 days of treatment initiation)
Albumin ≥ 3.0 g/dL (within 14 days of treatment initiation)
International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 14 days of treatment initiation)
Activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 14 days of treatment initiation)

Prior therapy with irinotecan (for expansion phase II only)
History of any second malignancy in the last 5 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible; subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years
Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion
New York Heart Association (NYHA) class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
Active infection or an unexplained fever > 38.5 degrees Celsius (C) during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumor fever may be enrolled), which in the investigator's opinion might compromise the patient's participation in the trial or affect the study outcome
Known hypersensitivity to any of the components of nal-IRI, other liposomal products, fluoropyrimidines or leucovorin
Investigational therapy administered within 4 weeks, 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 in this study
Any other medical or social condition deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results
Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment based on a urine or serum pregnancy test; both male and female patients of reproductive potential must agree to use a reliable method of birth control, during the study and for 3 months following the last dose of study drug
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Inability to take oral medications
Homozygous for the UGT1A1*28 allele (UGT1A1 7/7 genotype) only for the phase I part; heterozygotes for UGT1A1*28 (UGT1A11 7/6 genotype) will be allowed to enroll on the trial
Patients who are not appropriate candidates for participation in this clinical study for any other reason as deemed by the investigator
Patients with history of positive dihydropyrimidine dehydrogenase (DPD) deficiency

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Taiho Oncology, Inc.
Ipsen

Investigators

PRINCIPAL_INVESTIGATOR: Olatunji B. Alese, MD, Emory University

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record

Study Overview

Study Record Dates

Study Plan

Design Details

Contacts and Locations

Participation Criteria

Collaborators and Investigators

Publications

Treat yourself

Let Us Take Care Of You

About

Events

Fundraising

Contact Us

Learn

Resources

Patients

Caregivers

Learn

Resources

PatientS

Caregivers

Clinical Trial Record