Nanoliposomal Irinotecan in Head & Neck and Esophagus After Prior Platinum-based Chemotherapy or Chemoradiotherapy

Phase 2 Study of Nanoliposomal Irinotecan (Nal-IRI, PEP02, MM-398, Onivyde®) With 5-FU and Leucovorin in Squamous Cell Carcinoma (SCC) of Head & Neck and Esophagus After Prior Platinum-based Chemotherapy or Chemoradiotherapy

This is an open-label, single arm, multicenter phase 2 study. The study is to evaluate the activity of a combination therapy with nal-IRI (PEP02, MM-398, Onivyde®) plus 5-FU and leucovorin in patients with squamous cell carcinoma of head & neck and esophagus failed to platinum-based treatment in prior chemotherapy or chemoradiotherapy. The primary endpoint is to assess the objective tumor response rate (ORR). Eligible patients will be enrolled to receive combination therapy of nal-IRI plus 5-FU and Leucovorin on day 1, every 2 weeks. Every 2 weeks will be counted as one cycle. Treatment will continue until disease progression, unacceptable toxicity or other condition meeting the discontinuation criteria.

Study Overview

• Status: Completed
• Conditions: Head & Neck Cancer
• Intervention / Treatment: Drug: nanoliposomal irinotecan

Detailed Description

This is a phase 2, multicenter, uncontrolled, open-labeled, and one-arm study. Eligible patients will be treated with combination therapy of nal-IRI 80 mg/m2 for 90 minutes, leucovorin 400 mg/m2 for 30 minutes and 5-FU 2400 mg/m2 for 46 hours in sequence at day 1, every 14 days counted as one cycle. Modification of treatment dose is allowed according to the toxicities occurred in the previous treatment cycle. Patients will be treated until disease progression, unacceptable toxicity or other condition meeting the treatment discontinuation criteria.

Tumor response will be assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) every 6 weeks.

Adverse events (AEs) will be evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

Tumor marker response of SCC antigen will be evaluated by the change of serum SCC antigen level every 6 weeks. Tumor marker response is defined as a decrease of SCC antigen after treatment in relation to the pretreatment level.

Patients sign additional consent to participate in the pharmacogenetic and serum biomarker evaluation will be required to have extra blood samplings at the study entry and every 6 weeks thereafter for up to the maximum 4 times.

A follow-up visit is required approximately 30 days after treatment discontinuation. Overall survival status will be followed by clinic visit or by phone every 3 months until death or the maximum of 3 years, whichever occurs first.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan
    • China Medical University Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with ages ≥ 20 years old
2. Histologically confirmed squamous cell carcinoma of esophageal or head & neck cancers with exclusion of nasopharyngeal carcinoma
3. Unresectable locally advanced, recurrent or metastatic diseases ineligible or unsuitable for further surgical or radiation interventions
4. Documented disease progression within 6 months after treatment by prior platinum-based systemic chemotherapy or concurrent chemoradiotherapy. Patients who are intolerable to platinum-based systemic chemotherapy after at least 6 weeks' treatment interval or concurrent chemoradiotherapy after at least 3 weeks' treatment interval will be also eligible. Patients who have prior anti-EGFR and anti-PD1/anti-PDL1 treatment will be still eligible.
5. ECOG Performance Status 0 and 1
6. Documented measurable disease as defined by RECIST v1.1
7. Adequate hematologic parameters, and hepatic and renal functions defined as :absolute neutrophil count ≥ 1,500/μL , platelets ≥ 100,000/μL ,total bilirubin: within normal range ,AST/ALT ≤ 2.5X ULN (≤ 5X ULN if attributable to liver metastases) ,serum creatinine ≤ 2 mg/dL OR creatinine clearance ≥ 40 mL/min (by calculated or 24-hour urine collection)
8. Normal ECG or ECG without any clinical significant findings
9. Recovered from the effects of any prior surgery, radiotherapy, or other anti- neoplastic therapy
10. Able to understand and sign an informed consent (or have a legal representative who is able to do so) (According to inclusion criteria 3 and 4, four distinct patient populations will be enrolled with the following characterizations. (1) patients with metastatic diseases have disease progression while on or within 6 months after last dose of platinum-based chemotherapy; (2) patients with locally advanced diseases have disease progression while on or within 6 months after last dose of platinum-based chemotherapy or chemoradiotherapy; (3) patients with locally advanced diseases have a clinical complete response after platinum-based chemotherapy or chemoradiotherapy. However, the diseases recur within 6 months after completion of treatment and further local treatment were not indicated; (4) patients with metastatic or locally advanced disease but are intolerable to platinum-based chemotherapy after at least 6 weeks' treatment interval or chemoradiotherapy after at least 3 weeks' treatment interval.)

Exclusion Criteria:

1. Received prior nal-IRI (PEP02, MM-398, Onivyde) or irinotecan therapy
2. History of allergic reaction to liposome product, fluropyrimidines, or leucovorin
3. Patient with liver cirrhosis with Child-Pugh score ≥ 8 (Late Child-Pugh B and Child-Pugh C)
4. Active CNS metastasis defined by clinical symptoms, cerebral edema, steroid or anti-convulsant requirement, or progressive growth. Patients with a history of CNS metastasis or cord compression are allowed in the study if they have been treated and are clinically stable
5. With clinically significant gastrointestinal disorder including bleeding, inflammation, occlusion or diarrhea > grade 1
6. With uncontrolled intercurrent illness that could limit study compliance or judged to be ineligible for the study by the investigators including, but not limited to, any of the following: ongoing or active infection requiring antibiotic treatment symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia psychiatric illness or social situation that would preclude study compliance
7. Any major surgery, radiotherapy or anti-cancer therapy within 2 weeks. Patients receiving feeding stomy, esophageal stent and tracheal stent are still eligible to the study
8. History of other primary malignancy within 5 years except curatively treated non-melanoma skin cancer or treated cervical carcinoma in situ, or stage 1 to stage 3 head and neck cancer which is disease-free for two or more years.
9. Pregnant or breast feeding women (a urine pregnancy test must be performed on all patients who are of childbearing potential before entering the study, and the result must be negative)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nal-IRI in Head & Neck cancer; nal-IRI 80 mg/m2 for 90 minutes in sequence at day 1, every 14 days counted as one cycle	Drug: nanoliposomal irinotecan; combination therapy of nal-IRI , leucovorin and 5-FU in sequence at day 1, every 14 days counted as one cycle; Other Names: nal-IRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective tumor response rate	Objective tumor response rate	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Progression-Free Survival (PFS)	2-year
Treatment toxicities and safety profiles	Treatment toxicities and safety profiles,assessed by CTCAE v5.0	2-year
UGT1A family - UGT1A1 and UGT1A9 with toxicity	to explore the association of the pharmacogenomic data including UGT1A family - UGT1A1 and UGT1A9 with toxicitytoxicity	2-year
cytokine and chemokine before and after treatment	to explore the change of serum cytokine and chemokine before and after treatment	2-year

Collaborators and Investigators

• Sponsor: National Health Research Institutes, Taiwan
• Collaborators: China Medical University Hospital; Taipei Veterans General Hospital, Taiwan; National Cheng-Kung University Hospital; Tri-Service General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2018
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (Actual): October 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: April 9, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: T2317

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No