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

Phase 2

Completed

• Conditions: Neuroendocrine Carcinomas
• Interventions: Drug: TLC 388

• Registration Number: NCT02457273
• Lead Sponsor: National Health Research Institutes, Taiwan

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.

Study Timeline

• Study First Submitted: 2015-05-04
• Study First Submitted QC: 2015-05-26
• Study First Posted: 2015-05-29
• Study Start: 2015-07-04
• Primary Completion: 2018-04-18
• Status Verified: 2018-12
• Study Completion: 2018-12-01
• Last Update Submitted: 2019-04-01
• Last Update Posted: 2019-04-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Assigned Interventions	TLC 388	TLC 388

Primary Outcome Measures

Name	Time	Method
the objective response rate	5 years	Analysis for the objective response rate will be conducted on both the per protocol(PP) and evaluable data sets.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	5 years	Physical examinations, lab abnormality and other toxicities graded by the NCI Common Toxicity Criteria will be examined to evaluate safety profiles of the study treatments. Particular attention will be paid to Grade 3 or 4 toxicities.
Progression free survival	5 years	Progression-free survival will be calculated as the duration between the first date of randomization and the date of disease recurrence or progression according to RECIST v1.1 (failed), taking the status of tumor at the treatment has been completed as the reference, or death (failed), or the date of withdrawal (last contact date, censored), or the scheduled data analysis date (censored).
Disease control rate	5 years	The Disease control rate (DCR) is the percentage of subjects who have a best-response rating of CR or PR or SD (DCR= CR+PR+SD) (according to RECIST v1.1) when assessed after every 8 weeks of study drug (up to 6 cycles) and maintained for at least 28 days.
Overall survival	5 years	Overall survival will be calculated from the date of randomization to either the date of death from all causes, or to the date of withdrawal (last contact date, censored), or to the scheduled data analysis date (censored).

Trial Locations

Locations (7)

Chung Gung Memorial Hospital(Kaohsiung City); 🇨🇳 Kaohsiung, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

National Cheng-Kung University Hospital; 🇨🇳 Tainan, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Chang Gung Memorial Hospital (Lin-Kou),; 🇨🇳 Linkou, Taiwan