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

NCT ID: NCT02457273

Last Updated: 2019-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-04
• Study Completion Date: 2018-12-01

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.

Conditions

Neuroendocrine Carcinomas

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Assigned Interventions

TLC 388

Group Type: EXPERIMENTAL

TLC 388

Intervention Type: 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.

Interventions

TLC 388

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.

Intervention Type: DRUG

Other Intervention Names

Lipotecan®,

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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: collaborator

Taipei Veterans General Hospital, Taiwan

OTHER_GOV

Sponsor Role: collaborator

Taichung Veterans General Hospital

OTHER

Sponsor Role: collaborator

National Cheng-Kung University Hospital

OTHER

Sponsor Role: collaborator

Chang Gung Memorial Hospital

OTHER

Sponsor Role: collaborator

Kaohsiung Medical University Chung-Ho Memorial Hospital

OTHER

Sponsor Role: collaborator

National Health Research Institutes, Taiwan

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yee Chao, MD., PhD

Role: STUDY_CHAIR

Taipei Veterans General Hospital, Taiwan

Hui-Jen Tsai, MD., PhD

Role: STUDY_DIRECTOR

National Health Research of Institutes

Ming-Huang Chen, MD., PhD

Role: STUDY_DIRECTOR

Taipei Veterans General Hospital, Taiwan

Jen-Shi Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Cheng-Chung Wu, MS

Role: PRINCIPAL_INVESTIGATOR

Taichung Veterans General Hospital

Chiun Hsu, MD., PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Chia-Jui Yen, MD., PhD

Role: PRINCIPAL_INVESTIGATOR

National Cheng-Kung University Hospital

Yen-Yang Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Ta-Chih Liu, MD., PhD

Role: PRINCIPAL_INVESTIGATOR

Kaohsiung Medical University Chung-Ho Memorial Hospital

Locations

Chung Gung Memorial Hospital(Kaohsiung City)

Kaohsiung City, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Chang Gung Memorial Hospital (Lin-Kou),

Linkou District, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng-Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Countries

Taiwan

References

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.

Reference Type: DERIVED

PMID: 31852810 (View on PubMed)

Other Identifiers

T1Z14

Identifier Type: -

Identifier Source: org_study_id