TAS102 in Combination With NAL-IRI in Advanced GI Cancers

TAS102 in Combination With NAL-IRI in Advanced GI Cancers

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https://clinicaltrials.gov/ct2/show/NCT03368963

PurposeThis 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 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.

Condition
Intervention
Phase
Colorectal AdenocarcinomaGastric AdenocarcinomaMetastatic Pancreatic AdenocarcinomaNon-Resectable CholangiocarcinomaStage IV Colorectal CancerStage IV Gastric CancerStage IV Pancreatic CancerStage IVA Colorectal CancerStage IVB Colorectal CancerUnresectable Pancreatic Carcinoma
Drug: Nanoliposomal IrinotecanDrug: Trifluridine and Tipiracil Hydrochloride
Phase 1Phase 2

Study Type:
Interventional
Study Design:
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title:
A Phase I/II Study of Trifluridine/Tipiracil (TAS102) in Combination With Nanoliposomal Irinotecan (NAL-IRI) in Advanced GI Cancers

Resource links provided by NLM:

Genetics Home Reference related topics: cholangiocarcinoma
Drug Information available for: Trifluridine Irinotecan Irinotecan hydrochloride
Genetic and Rare Diseases Information Center resources: Bile Duct Cancer Stomach Cancer
U.S. FDA Resources

Further study details as provided by Olatunji Alese, Emory University:

Primary Outcome Measures:Incidence of adverse events of trifluridine/tipiracil hydrochloride combination agent TAS-102 in combination with nanoliposomal irinotecan [ Time Frame: Up to 3 years after end of treatment ]Assessed using Common Terminology Criteria for Adverse Events version 4.0.

Overall response rate based on modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 3 years after end of treatment ]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).

Secondary Outcome Measures:Progression free survival [ Time Frame: Up to 3 years after end of treatment ]Will be evaluated.

Response duration [ Time Frame: From initial response until documented tumor progression, assessed up to 3 years ]Will be estimated by Kaplan-Meier method. P values will be two-sided with significance level of .05.

Response rate [ Time Frame: Up to 3 years after end of treatment ]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.

Estimated Enrollment:
64
Anticipated Study Start Date:
December 1, 2018
Estimated Study Completion Date:
November 7, 2020
Estimated Primary Completion Date:
November 7, 2020 (Final data collection date for primary outcome measure)
Arms
Assigned Interventions
Experimental: Treatment (Nal-IRI, TAS-102)Patients receive nanoliposomal irinotecan IV over 90 minutes on day 1 and combination of trifluridine and tipiracil hydrochloride combination agent TAS-102 PO BID on days 1-5. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Nanoliposomal IrinotecanGiven IV
Other Names:Irinotecan Liposome
Onivyde
PEP02
Camptosar
Liposomal Irinotecan
Drug: Trifluridine and Tipiracil HydrochlorideGiven PO
Other Names:Lonsurf
TAS-102
Trifluridine/Tipiracil

Detailed Description: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. Courses 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.
Eligibility
Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:
18 Years and older   (Adult, Senior)
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Criteria
Inclusion Criteria:

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
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
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
Adequate organ function
Recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy
Exclusion Criteria:

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
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
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) or heterozygotes for UGT1A1*28 (UGT1A11 7/6 genotype) only for the phase I part
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
Other protocol defined inclusion/exclusion criteria could apply
Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03368963

Contacts

Contact: Olatunji B. Alese, MD
404-778-2670
olatunji.alese@emory.edu
Locations

United States, Georgia
Emory University Hospital Midtown
Not yet recruiting
Atlanta, Georgia, United States, 30308
Contact: Shabnam Montazeri    404-686-0242    shabnam.montazeri@emory.edu
Emory University Hospital/Winship Cancer Institute
Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Meredith Renfroe    404-778-2670    marenfr@emory.edu
Emory Saint Joseph’s Hospital
Not yet recruiting
Atlanta, Georgia, United States, 30342
Contact: Alicia Escobar    404-843-7029    alicia.m.escobar@emory.edu
Sponsors and Collaborators
Emory University
Taiho Oncology, Inc.
Ipsen
Investigators

Principal Investigator:
Olatunji B. Alese, MD
Emory University
More Information

Responsible Party:
Olatunji Alese, Principal Investigator, Emory University
ClinicalTrials.gov Identifier:
NCT03368963     History of Changes
Other Study ID Numbers:
IRB00098958
NCI-2017-01661 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Winship4146-17 ( Other Identifier: Emory University Hospital/Winship Cancer Institute )

First Submitted:
December 6, 2017
First Posted:
December 11, 2017
Last Update Posted:
December 12, 2017
Last Verified:
December 2017

Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No