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

• Status: Active, not recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

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

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

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)