Back to results

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

Primary Purpose

Neuroendocrine Carcinomas

Status

Completed

Phase

Phase 2

Locations

Taiwan

Study Type

Interventional

Intervention

TLC 388

About this trial

This is an interventional treatment trial for Neuroendocrine Carcinomas focused on measuring PDNC(Poorly Differentiated Neuroendocrine Carcinomas), TLC-388 (Lipotecan®)

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Chung Gung Memorial Hospital(Kaohsiung City)
Kaohsiung Medical University Chung-Ho Memorial Hospital
Chang Gung Memorial Hospital (Lin-Kou),
Taichung Veterans General Hospital
National Cheng-Kung University Hospital
National Taiwan University Hospital
Taipei Veterans General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Assigned Interventions

Arm Description

TLC 388

Outcomes

Primary Outcome Measures

the objective response rate

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

Secondary Outcome Measures

Disease control rate

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.

Progression free survival

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).

Overall survival

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).

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

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.

Full Information

NCT ID

NCT02457273

First Posted

May 4, 2015

Last Updated

April 1, 2019

Sponsor

National Health Research Institutes, Taiwan

Collaborators

National Taiwan University Hospital, Taipei Veterans General Hospital, Taiwan, Taichung Veterans General Hospital, National Cheng-Kung University Hospital, Chang Gung Memorial Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02457273

Brief Title

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

2. Study Status

Record Verification Date

December 2018

Overall Recruitment Status

Completed

Study Start Date

July 4, 2015 (Actual)

Primary Completion Date

April 18, 2018 (Actual)

Study Completion Date

December 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Health Research Institutes, Taiwan

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuroendocrine Carcinomas

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

23 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Assigned Interventions

Arm Type

Experimental

Arm Description

TLC 388

Intervention Type

Drug

Intervention Name(s)

TLC 388

Other Intervention Name(s)

Lipotecan®,

Intervention Description

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.

Primary Outcome Measure Information:

Title

the objective response rate

Description

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

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Disease control rate

Description

Time Frame

5 years

Title

Progression free survival

Description

Time Frame

5 years

Title

Overall survival

Description

Time Frame

5 years

Title

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

Description

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials: