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

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ClinicalTrials.gov Identifier: NCT03712397
Recruitment Status : Not yet recruiting
First Posted : October 19, 2018
Last Update Posted : October 19, 2018
Sponsor:
Collaborators:
China Medical University Hospital
Tri-Service General Hospital
Taipei Veterans General Hospital, Taiwan
National Cheng-Kung University Hospital
Information provided by (Responsible Party):
National Health Research Institutes, Taiwan

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.

Condition or disease Intervention/treatment Phase
Head & Neck Cancer Drug: nanoliposomal irinotecan Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : October 15, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


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 Name: nal-IRI




Primary Outcome Measures :
  1. Objective tumor response rate [ Time Frame: 6 weeks ]
    Objective tumor response rate


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: 2-year ]
    Progression-Free Survival (PFS)

  2. Treatment toxicities and safety profiles [ Time Frame: 2-year ]
    Treatment toxicities and safety profiles,assessed by CTCAE v5.0

  3. UGT1A family - UGT1A1 and UGT1A9 with toxicity [ Time Frame: 2-year ]
    to explore the association of the pharmacogenomic data including UGT1A family - UGT1A1 and UGT1A9 with toxicitytoxicity

  4. cytokine and chemokine before and after treatment [ Time Frame: 2-year ]
    to explore the change of serum cytokine and chemokine before and after treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03712397


Contacts
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Contact: Ya-Ling Wu, BS 886-3-7246166 ext 35119 yalin@nhri.org.tw

Locations
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Taiwan
China Medical University Hospital Not yet recruiting
Taichung, Taiwan
Sub-Investigator: Chen Yuan Lin, PhD         
Sub-Investigator: Ching Yun Hsieh, MD         
Sub-Investigator: Ming-Yu Lien, MD         
National Cheng Kung University Hospital Not yet recruiting
Tainan, Taiwan
Sub-Investigator: Chia-Jui Yen, PhD         
Sub-Investigator: Wen-Pin Su, PhD         
Sub-Investigator: Shang-Yin Wu, PhD         
Sub-Investigator: Li-Tzong Chen, PhD         
Sub-Investigator: Kwang-Yu Chang, PhD         
Sub-Investigator: Hui-jen Tsai, PhD         
Sub-Investigator: Shang-Hung Chen, PhD         
Sub-Investigator: Nai-Jung Chiang, PhD         
Taipei Veterans General Hospital Not yet recruiting
Taipei, Taiwan
Sub-Investigator: Muh-Hwa Yang, PhD         
Sub-Investigator: Sheng-Yu Chen, MD         
Sub-Investigator: Mu-Hsin Chang, PhD         
Tri-Service General Hospital Not yet recruiting
Taipei, Taiwan
Sub-Investigator: Ching Liang Ho, MD         
Sub-Investigator: Yeu Chin Chen, MD         
Sub-Investigator: Ming Shen Dai, PhD         
Sub-Investigator: Ping Ying Chang, MD         
Sub-Investigator: Yi Ying Wu, MD         
Sub-Investigator: Tzu Chuan Huang, MD         
Sub-Investigator: Jia Hong Chen, MD         
Sub-Investigator: Ren Hua Ye, MD         
Sub-Investigator: Shiue Wei Lai, Md         
Sponsors and Collaborators
National Health Research Institutes, Taiwan
China Medical University Hospital
Tri-Service General Hospital
Taipei Veterans General Hospital, Taiwan
National Cheng-Kung University Hospital
Investigators
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Principal Investigator: Li-Yuan Bai, PhD China Medical University Hospital

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Responsible Party: National Health Research Institutes, Taiwan
ClinicalTrials.gov Identifier: NCT03712397     History of Changes
Other Study ID Numbers: T2317
First Posted: October 19, 2018    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Irinotecan
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents