Clinical trial NCT02457273: Phase II Study to Evaluate the Efficacy and Safety of TLC388 for Differentiated Neuroendocrine Carcinomas Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Carcinomas
Keywords: PDNC(Poorly Differentiated Neuroendocrine Carcinomas)
TLC-388 (Lipotecan®)
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
Collaborators: name: National Taiwan University Hospital
name: Taipei Veterans General Hospital, Taiwan
name: Taichung Veterans General Hospital
name: National Cheng-Kung University Hospital
name: Chang Gung Memorial Hospital
name: Kaohsiung Medical University Chung-Ho Memorial Hospital
First posted: 2015-05-29
Enrollment: 23
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: This is a phase II, open-label, single-arm, two-stage, multicenter study to evaluate the efficacy and safety of Lipotecan® monotherapy in subjects with poorly differentiated neuroendocrine carcinomas. Only those subjects who have failed to first line chemotherapy (Etoposide plus platinum) due to treatment intolerance or radiographic progressive disease (PD), as per RECIST v1.1, are eligible to participate in the study. The scheduled assessments should be performed as identified on a calendar schedule, and should not be affected by delays in therapy, drug holidays or any other events that might be lead to imbalance in a treatment arm in the timing of disease assessment. Efficacy results are based on radiographic assessments reviewed by the investigator.

Eligible subjects will receive 40 mg/m2 of Lipotecan®, 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.

Eligibility criteria: Inclusion Criteria:

1. Pathologically confirmed poorly differentiated neuroendocrine carcinomas.
2. 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).
3. At least one measurable lesion in a non-irradiated area.
4. Aged \> 20 years old.
5. ECOG Performance Status ≤ 2.
6. Life expectancy greater than 12 weeks.
7. Adequate bone marrow function :

   * absolutely neutrophil count ≥ 1500 /mm3 or WBC ≥ 4000/mm3
   * Hemoglobin \> 9 g/dl
   * platelet count ≥ 100,000 /mm3
8. 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
9. Adequate renal function: creatinine \< 1.5 x ULN.
10. Subjects who are willing and able to comply with all of the study procedures, and able to sign the informed consent.

Exclusion Criteria:

1. Major surgery within two weeks prior to entering the study.
2. Patients with CNS metastasis, including clinical suspicion.
3. Patients who are under active or uncontrolled infections.
4. Patients with concomitant illness that might be aggravated by chemotherapy.
5. Patients who are pregnant or with breast feeding.
6. 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.
7. Fertile men and women unless using a reliable and appropriate contraceptive method
8. 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.
9. Patients with a known history of human immunodeficiency virus infection.
10. The presence of active or uncontrolled systemic infection (bacterial, viral, other) except for chronic hepatitis B and hepatitis C.
11. Use of any investigational agent within 4 weeks of baseline.
12. 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.
13. Known hypersensitivity or adverse drug reactions to Lipotecan® or its components.

Primary outcomes:
measure: the objective response rate
timeFrame: 5 years
Secondary outcomes:
measure: Disease control rate
timeFrame: 5 years
measure: Progression free survival
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 5 years
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Chung Gung Memorial Hospital(Kaohsiung City)
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Linkou
country: Taiwan
facility: Chang Gung Memorial Hospital (Lin-Kou),
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng-Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Taipei Veterans General Hospital, Taiwan
name: Yee Chao, MD., PhD
role: STUDY_CHAIR
affiliation: National Health Research of Institutes
name: Hui-Jen Tsai, MD., PhD
role: STUDY_DIRECTOR
affiliation: Taipei Veterans General Hospital, Taiwan
name: Ming-Huang Chen, MD., PhD
role: STUDY_DIRECTOR
affiliation: Chang Gung Memorial Hospital
name: Jen-Shi Chen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Taichung Veterans General Hospital
name: Cheng-Chung Wu, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University Hospital
name: Chiun Hsu, MD., PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cheng-Kung University Hospital
name: Chia-Jui Yen, MD., PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chang Gung Memorial Hospital
name: Yen-Yang Chen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kaohsiung Medical University Chung-Ho Memorial Hospital
name: Ta-Chih Liu, MD., PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.