Phase II Study to Evaluate the Efficacy and Safety of TLC388 for Differentiated Neuroendocrine Carcinomas Patients

NCT02457273 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: T1Z14
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 7

Brief Summary

Title of Study: An Open-Label, Single-Arm, Two-Stage, Multicenter, Phase II Study to Evaluate the Efficacy and Safety of TLC388 as Second-line Treatment in Subjects with Poorly Differentiated Neuroendocrine Carcinomas Investigational product: Lipotecan®\* \*Lipotecan® is the trade name of TLC388 HCl, a Topoisomerase I inhibitor) Phase of development: Phase II Number of subjects: Plan to enroll 44 subjects Objectives: Primary objectives: To determine the objective response rate Secondary objectives: To evaluate Disease control rate, Progression free survival, Overall survival, Safety profile and Biomarkers

Conditions

Neuroendocrine Carcinomas

Keywords

PDNC(Poorly Differentiated Neuroendocrine Carcinomas); TLC-388 (Lipotecan®)

Outcome Measures

Primary Outcomes (1)

• the objective response rate

  Analysis for the objective response rate will be conducted on both the per protocol(PP) and evaluable data sets.

  5 years

Secondary Outcomes (4)

• Disease control rate

  5 years

• Progression free survival

  5 years

• Overall survival

  5 years

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  5 years

Study Arms (1)

Assigned Interventions

EXPERIMENTAL

TLC 388

Drug: TLC 388

Interventions

TLC 388 DRUG

40 mg/m2 of TLC 388, given as a 30 (+3) minute intravenous infusion, on Days 1, 8 and 15 of a 28-day cycle until PD, unacceptable toxicity or consent withdrawal occurs.

Also known as: Lipotecan®,

Assigned Interventions

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed poorly differentiated neuroendocrine carcinomas.
• Patients who had first-line treatment failure (First line therapy must be etoposide plus platinum) due to treatment intolerance or radiographic progressive disease (as per RECIST v1.1).
• At least one measurable lesion in a non-irradiated area.
• Aged \> 20 years old.
• ECOG Performance Status ≤ 2.
• Life expectancy greater than 12 weeks.
• Adequate bone marrow function :
• absolutely neutrophil count ≥ 1500 /mm3 or WBC ≥ 4000/mm3
• Hemoglobin \> 9 g/dl
• platelet count ≥ 100,000 /mm3
• Adequate liver function :
• ALT \& AST ≤ 2.5 x ULN if without liver metastasis or ≤ 5 x ULN if with hepatic metastasis Alkaline phosphatase ≤ 2.5 x ULN if without liver and bone metastasis; or ≤ 5 x ULN if with hepatic metastasis or bone metastasis
• Total Bilirubin \< 2 x ULN
• Adequate renal function: creatinine \< 1.5 x ULN.
• Subjects who are willing and able to comply with all of the study procedures, and able to sign the informed consent.

You may not qualify if:

• Major surgery within two weeks prior to entering the study.
• Patients with CNS metastasis, including clinical suspicion.
• Patients who are under active or uncontrolled infections.
• Patients with concomitant illness that might be aggravated by chemotherapy.
• Patients who are pregnant or with breast feeding.
• Other concomitant or previously malignancy within 5 yrs except for in situ cervix cancer or squamous cell carcinoma of the skin treated by surgery only.
• Fertile men and women unless using a reliable and appropriate contraceptive method
• A history of or the presence of one or more cardiac diseases, such as congestive heart failure (New York Heart Association Class III or IV), myocardial infarction or unstable angina and related surgeries, within 3 months prior to the initiation of the treatment dose.
• Patients with a known history of human immunodeficiency virus infection.
• The presence of active or uncontrolled systemic infection (bacterial, viral, other) except for chronic hepatitis B and hepatitis C.
• Use of any investigational agent within 4 weeks of baseline.
• Uncontrolled and unstable concurrent medical or psychiatric illness that will jeopardize the safety of the subject, interfere with the objectives of the protocol, or affect the subject compliance with study requirements, as determined by the investigator.
• Known hypersensitivity or adverse drug reactions to Lipotecan® or its components.

Sponsors & Collaborators

• National Health Research Institutes, Taiwan: lead
• National Taiwan University Hospital: collaborator
• Taipei Veterans General Hospital, Taiwan: collaborator
• Taichung Veterans General Hospital: collaborator
• National Cheng-Kung University Hospital: collaborator
• Chang Gung Memorial Hospital: collaborator
• Kaohsiung Medical University Chung-Ho Memorial Hospital: collaborator

Study Sites (7)

Chung Gung Memorial Hospital(Kaohsiung City)

Kaohsiung City, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Location

Chang Gung Memorial Hospital (Lin-Kou),

Linkou District, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

National Cheng-Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Related Publications (1)

• Chen MH, Chou WC, Hsiao CF, Jiang SS, Tsai HJ, Liu YC, Hsu C, Shan YS, Hung YP, Hsich CH, Chiu CH, Liu TC, Cho SF, Liu TW, Chao Y. An Open-Label, Single-Arm, Two-Stage, Multicenter, Phase II Study to Evaluate the Efficacy of TLC388 and Genomic Analysis for Poorly Differentiated Neuroendocrine Carcinomas. Oncologist. 2020 May;25(5):e782-e788. doi: 10.1634/theoncologist.2019-0490. Epub 2019 Dec 18.

  PMID: 31852810 DERIVED

MeSH Terms

Conditions

Carcinoma, Neuroendocrine

Interventions

TLC 388

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Yee Chao, MD., PhD

  Taipei Veterans General Hospital, Taiwan

  STUDY CHAIR

• Hui-Jen Tsai, MD., PhD

  National Health Research of Institutes

  STUDY DIRECTOR

• Ming-Huang Chen, MD., PhD

  Taipei Veterans General Hospital, Taiwan

  STUDY DIRECTOR

• Jen-Shi Chen, MD

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

• Cheng-Chung Wu, MS

  Taichung Veterans General Hospital

  PRINCIPAL INVESTIGATOR

• Chiun Hsu, MD., PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

• Chia-Jui Yen, MD., PhD

  National Cheng-Kung University Hospital

  PRINCIPAL INVESTIGATOR

• Yen-Yang Chen, MD

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

• Ta-Chih Liu, MD., PhD

  Kaohsiung Medical University Chung-Ho Memorial Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2015
• First Posted: May 29, 2015
• Study Start: July 4, 2015
• Primary Completion: April 18, 2018
• Study Completion: December 1, 2018
• Last Updated: April 3, 2019

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (7)