Nanoliposomal Irinotecan (Nal-IRI, ONIVYDE®) in Combination With TAS-102 (LONSURF®) in Refractory Solid Tumors

• ClinicalTrials.gov Identifier: NCT03810742
• Recruitment Status: Active, not recruiting
• First Posted: January 22, 2019
• Last Update Posted: September 17, 2021
• Sponsor: PharmaEngine
• Information provided by (Responsible Party): PharmaEngine

Tracking Information

• First Submitted Date: December 21, 2018
• First Posted Date: January 22, 2019
• Last Update Posted Date: September 17, 2021
• Actual Study Start Date: March 5, 2019
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 17, 2019)

• Determination of Dose Limiting Toxicities (DLT) [ Time Frame: 12 months ]
  to find the Dose Limiting Toxicity (DLT) of nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®)
• Evaluation of Safety profile of nal-IRI and TAS-102 - Incidence of Treatment-Emergent Adverse Events [ Time Frame: 12 months ]
  Incidence of Treatment-Emergent Adverse Events [Safety] of nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®) according to NCI-CTCAE version 5.0

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 17, 2019)

• Evaluation of objective tumor response as per Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 24 months ]
  the objective tumor rate by using RECIST v1.1
• Pharmacokinetics study - (Cmax) [ Time Frame: 6 months ]
  Concentration of Peak Plasma (Cmax)
• Pharmacokinetics study - (Tmax) [ Time Frame: 6 months ]
  maximum concentration of the time taken to reach the (Tmax).
• Pharmacokinetics study - (T1/2) [ Time Frame: 6 months ]
  time of C max to drop in half taken (T1/2)
• Pharmacokinetics study - (AUC0→t) [ Time Frame: 6 months ]
  area of the plasma concentration versus time curve (AUC0→t).
• Pharmacokinetics study - (AUC0→∞) [ Time Frame: 6 months ]
  area of the plasma concentration versus under curve (AUC0→∞)
• Pharmacokinetics study - (CL) [ Time Frame: 6 months ]
  rate of clearance (CL)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nanoliposomal Irinotecan (Nal-IRI, ONIVYDE®) in Combination With TAS-102 (LONSURF®) in Refractory Solid Tumors
• Official Title: Phase 1 Study of Nanoliposomal Irinotecan (Nal-IRI, ONIVYDE®) in Combination With TAS-102 (LONSURF®) in Refractory Solid Tumors
• Brief Summary: The study is to explore the combination of nal-IRI and TAS-102, which is expected to be an effective regimen that could be applied to various cancers

Detailed Description

Primary Objectives

• to determine the maximum tolerated dose (MTD) of nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®)
• to evaluate the toxicity profile of the combination therapy Secondary Objectives
• to evaluate the preliminary efficacy of the combination therapy of nal-IRI (ONIVYDE®) and TAS-102 (LONSURF®)
• to study the pharmacokinetics of the combination therapy

A phase 1 study with a classical 3 + 3 dose escalation design. The target population is patients who have pathologically confirmed malignant solid tumors with no standard treatment available.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Refractory Solid Tumors

Intervention

Drug: Nanoliposomal Irinotecan

Nanoliposomal Irinotecan (nal-IRI, ONIVYDE®) in Combination with TAS-102 (LONSURF®)

Other Name: TAS-102

Study Arms

Experimental: Nanoliposomal Irinotecan + TAS-102

different dosage combination by Nanoliposomal Irinotecan (nal-IRI, ONIVYDE®) in Combination with TAS-102 (LONSURF®)

Intervention: Drug: Nanoliposomal Irinotecan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: September 16, 2021): 44
• Original Estimated Enrollment (submitted: January 17, 2019): 57
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Ages between 20 to 70 years old
2. Histologically or cytologically confirmed malignant solid tumors which are advanced or metastatic, have failed standard treatment or have no standard treatment currently available
3. ECOG performance status 0 or 1
4. Normal ECG or ECG without any clinically significant findings
5. Adequate hematologic parameters, and hepatic and renal function i. White blood cell (WBC) count 3000/μL and absolute neutrophil count (ANC) 1500/μL ii. Platelet counts 100,000/μL without platelet transfusion within 14 days iii. Hemoglobin level 10 g/dL iv. Serum total bilirubin- within normal range v. Serum albumin 3.0 g/dL vi. Serum alanine aminotransferase (ALT) 3 x the upper limit of normal (ULN) vii. Serum creatinine 1.5 x ULN

Exclusion Criteria:

1. Received prior nal-IRI (ONIVYDE®) or TAS-102 (LONSURF®) therapy
2. Known hypersensitivity to any of the components of nal-IRI, other liposomal products, fluoropyrimidines or leucovorin
3. Have liver cirrhosis with Child-Pugh B or Child-Pugh C
4. With active CNS metastasis (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive growth)
5. With clinically significant gastrointestinal disorder including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1
6. Life expectancy of less than 3 months
7. Use any anti-cancer or investigational product within 14 days prior to the first date of study dosing
8. History of any second malignancy in the latest 5 years except curatively treated non-melanoma skin cancer or treated cervical carcinoma in situ
9. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection requiring antibiotic treatment, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia, and psychiatric illness or social situation that would preclude study compliance
10. Homozygous for the UGT1A1 28 allele (TA7/TA7), homozygous for UGT1A1 6 allele (A/A), or double heterozygous for both UGT1A1 28 allele (TA6/TA7) and UGT1A1 6 allele (G/A) (only for dose-finding phase)
11. Pregnant or breastfeeding women

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT03810742
• Other Study ID Numbers: PEP0210
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: PharmaEngine
• Study Sponsor: PharmaEngine
• Collaborators: Not Provided

Investigators

• Principal Investigator: Chia-Chi Lin, MD; National Taiwan University Hospital, Taipei, Taiwan

• PRS Account: PharmaEngine
• Verification Date: September 2021