Colorectal AdenocarcinomaPhase 1/2NCT03368963

TAS102 in Combination With NAL-IRI in Advanced GI Cancers

A Phase 1/2 study testing Nanoliposomal Irinotecan and Trifluridine and Tipiracil Hydrochloride in people with Colorectal Adenocarcinoma and Gastric Adenocarcinoma, run by Emory University at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Colorectal Adenocarcinoma, Gastric Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma
What is being tested?: Nanoliposomal Irinotecan and Trifluridine and Tipiracil Hydrochloride
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 64 participants
Where: 3 sitesUnited States
Study dates: 30 Jan 2018to 28 Nov 2025
Phase: Phase 1/2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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)

Who cannot join

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

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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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342

Other trials in United States

About this study

Official title: A Phase I/II Study of Trifluridine/Tipiracil (TAS102) in Combination With Nanoliposomal Irinotecan (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.

Read the detailed description

PRIMARY OBJECTIVES:

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:

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.

Conditions: Colorectal Adenocarcinoma, Gastric Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma, Non-Resectable Cholangiocarcinoma, Stage IV Colorectal Cancer, Stage IV Gastric Cancer
Being tested: Nanoliposomal Irinotecan, Trifluridine and Tipiracil Hydrochloride
Medical subject headings: Colorectal Neoplasms, Stomach Neoplasms, Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Nanoliposomal IrinotecanDrug
Also called Irinotecan Liposome, Onivyde, PEP02, Camptosar
Given IV
Trifluridine and Tipiracil HydrochlorideDrug
Also called Lonsurf, TAS-102, Trifluridine/Tipiracil
Given PO

Study groups in NCT03368963
Study group	Role	What they receive
Treatment (Nal-IRI, TAS-102)	Experimental	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 toxicity. Receives: Drug: Nanoliposomal Irinotecan; Drug: Trifluridine and Tipiracil Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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).
Measured: Up to 3 years after end of treatment

Secondary outcomes (3)

Progression free survival
Will be evaluated.
Measured: 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.
Measured: 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.
Measured: Up to 3 years after end of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Jan 201828 Nov 2025

First posted11 Dec 2017
Study start30 Jan 2018
Primary completion28 Jun 2025 (estimated)
Study completion28 Nov 2025 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Colorectal AdenocarcinomaStudies of the same condition, open and under way.
More trials run by Emory UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 64 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03368963
Sponsor's protocol ID: IRB00098958
Other IDs: NCI-2017-01661, Winship4146-17
Status last verified: Jan 2025
First submitted: 6 Dec 2017
Last updated: 7 Jan 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 7 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Study of Trifluridine/Tipiracil (TAS102) in Combination With Nanoliposomal Irinotecan (NAL-IRI) in Advanced GI Cancers
ClinicalTrials.gov ID: NCT03368963
Acronym / sponsor ID: IRB00098958
Conditions: Colorectal Adenocarcinoma, Gastric Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma, Non-Resectable Cholangiocarcinoma, Stage IV Colorectal Cancer, Stage IV Gastric Cancer
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 64 participants (estimated)
Lead sponsor: Emory UniversityUniversity, hospital or other
Collaborators: Taiho Oncology, Inc., Ipsen
Study start: 30 Jan 2018 (actual)
Primary completion: 28 Jun 2025 (estimated)
Study completion: 28 Nov 2025 (estimated)
First posted: 11 Dec 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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:

Define the toxicity profile of the combination of TAS-102 and nal-IRI.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

After completion of study treatment, patients are followed up for 30 days and then every 8 or 12 weeks thereafter.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment (Nal-IRI, TAS-102)	Experimental	Drug: Nanoliposomal Irinotecan, Drug: Trifluridine and Tipiracil HydrochloridePatients 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 toxicity.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

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

Key exclusion criteria (15 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Nanoliposomal IrinotecanAlso: Irinotecan Liposome, Onivyde, PEP02, CamptosarGiven IV	Drug	Treatment (Nal-IRI, TAS-102)
Trifluridine and Tipiracil HydrochlorideAlso: Lonsurf, TAS-102, Trifluridine/TipiracilGiven PO	Drug	Treatment (Nal-IRI, TAS-102)

Primary outcome

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).

3 secondary outcomes

Progression free survival
Time frame: Up to 3 years after end of treatment
Response duration
Time frame: From initial response until documented tumor progression, assessed up to 3 years
Response rate
Time frame: Up to 3 years after end of treatment

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2025.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Olatunji B. Alese, MD principal investigator

Emory University

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03368963.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2025.