Summary

This phase I/II trial studies the best dose and how well trifluridine/tipiracil hydrochloride combination agent TAS-102 (TAS-102) and liposomal irinotecan work in treating patients with gastrointestinal cancers that have spread to nearby tissue and lymph nodes (locally advanced), 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 liposomal 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.

Objectives

PRIMARY OBJECTIVES:
I. Determine the recommended phase II dose for the combination of TAS-102 and liposomal 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 activity 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 liposomal 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.

Eligibility

1. 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
2. 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
3. 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
4. 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
5. 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
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
7. Adequate renal function as evidenced by a serum creatinine =< 1.5 x upper limit of normal (ULN)
8. Recovered from the effects of any prior surgery, radiotherapy or other antineoplastic therapy
9. At least 18 years of age
10. Able to understand and sign an informed consent (or have a legal representative who is able to do so)
11. 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
12. 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
13. 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
14. Absolute neutrophil count (ANC) >= 1,500/ul without the use of hematopoietic growth factors (within 14 days of treatment initiation)
15. Platelets >= 100,000/ul (within 14 days of treatment initiation)
16. Hemoglobin >= 8 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 8 g/dL) (within 14 days of treatment initiation)
17. 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
18. Serum total bilirubin within normal range for the institution (biliary drainage is allowed for biliary obstruction) (within 14 days of treatment initiation)
19. 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)
20. Albumin >= 3.0 g/dL (within 14 days of treatment initiation)
21. 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)
22. 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)

Treatment Sites in Georgia