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

NCT ID: NCT03712397

Last Updated: 2023-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-24
• Study Completion Date: 2022-12-31

Brief Summary

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.

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.

Conditions

Head & Neck Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

nanoliposomal irinotecan

Intervention Type: DRUG

combination therapy of nal-IRI , leucovorin and 5-FU in sequence at day 1, every 14 days counted as one cycle

Interventions

nanoliposomal irinotecan

combination therapy of nal-IRI , leucovorin and 5-FU in sequence at day 1, every 14 days counted as one cycle

Intervention Type: DRUG

Other Intervention Names

nal-IRI

Eligibility Criteria

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

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)

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

China Medical University Hospital

OTHER

Sponsor Role: collaborator

Tri-Service General Hospital

OTHER

Sponsor Role: collaborator

Taipei Veterans General Hospital, Taiwan

OTHER_GOV

Sponsor Role: collaborator

National Cheng-Kung University Hospital

OTHER

Sponsor Role: collaborator

National Health Research Institutes, Taiwan

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li-Yuan Bai, PhD

Role: PRINCIPAL_INVESTIGATOR

China Medical University Hospital

Locations

China Medical University Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Countries

Taiwan

References

Yang MH, Wu SY, Ho IW, Chiang NJ, Hsaio CF, Lin CY, Lien MY, Chang PM, Chen JH, Hsieh CY, Hong RL, Lee CT, Chen LT, Liu TW, Chiu CF, Bai LY. Nanoliposomal Irinotecan in Combination With 5-Fluorouracil and Leucovorin for Advanced Head and Neck and Esophageal Squamous Cell Carcinoma After Prior Platinum-Based Chemotherapy or Chemoradiotherapy: A Multicenter Phase II Trial. Cancer Med. 2025 Oct;14(20):e71307. doi: 10.1002/cam4.71307.

Reference Type: DERIVED

PMID: 41117518 (View on PubMed)

Other Identifiers

T2317

Identifier Type: -

Identifier Source: org_study_id