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Multicenter Randomized Controlled Trial Adjuvant Chemotherapy vs Observation in pStage Ib Lung Adenocarcinoma

Primary Purpose

Stage Ib Lung Carcinoma

Status

Unknown status

Phase

Phase 3

Locations

Korea, Republic of

Study Type

Interventional

Intervention

vinorelbine plus cisplatin

About this trial

This is an interventional treatment trial for Stage Ib Lung Carcinoma focused on measuring normogram, recurrence, adjuvant chemotherapy, disease free survival, Quality of life

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must meet ALL of the following criteria in order to be eligible for this study
Age ≥18 years and Age <80
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
The pathological stage Ib adenocarcinoma after complete resection (AJCC 7th). (Patients with adenocarcinoma in situ are excluded)
Patients must have undergone pulmonary resection more than lobectomy (lobectomy, bilobectomy, pneumonectomy).
Patients must have undergone either mediastinal lymph node dissection or systemic sampling.
Tumor must be resected completely without gross or microscopic residual tumor.
The interval between surgery for lung cancer and randomization must be no more than 8 weeks.
The patients must be willing and sign informed consent prior to randomization.
Patients with appropriate bone marrow function. ANC ≥1,500/uL, hemoglobin ≥9.0g/dL (can be corrected by transfusion). platelet ≥100,000/uL
Patients with appropriate renal function Serum creatinine ≤ 1 x UNL(upper limit or normal) or Estimated creatinine clearance ≥ 45 ml/min
Patients with appropriate liver function Serum bilirubin ≤ 1.5 x UNL, AST (SGOT) and ALT (SGPT) ≤ 3 x UNL, alkaline phosphatase ≤ 3 x UNL

Exclusion Criteria:

Patients meeting any ONE of the following criteria are not eligible for this study.
Other concurrent serious diseases that may interfere with planned treatment.
Pregnant of lactation women
Women of childbearing potential without a negative pregnant test (urine HCG), within 14 days prior to randomization or less than one year after menopause.
Any previous systemic chemotherapy for cancer or anti-cancer immunotherapy.
History of non-lung malignancies within the 5 years prior to study entry, except for the following: carcinoma in situ of the cervix, melanoma in situ.
Serious cardiac illness or medical conditions including uncontrolled hypertension, myocardial infarction within 6 months, unstable angina pectoris, heart failure >NYHA grad II, or uncontrolled arrhythmia.
Patients with sensitivity to vinorelbine or cisplatin.
Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol.

Sites / Locations

Seoul National University Bundang HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Arm Label

low risk

high risk; observation group

high risk; adjuvant chemotherapy group

Arm Description

low risk; observation

high risk: observation

high risk. vinorelbine plus cisplatin

Outcomes

Primary Outcome Measures

disease-free survival (DFS)

the time between the operation and the date of treatment for recurred lung cancer or suspected recurrence

Secondary Outcome Measures

overall survival rate (OS)

the time between the operation and death from any cause

quality-of-life (QoL)

Full Information

NCT ID

NCT02281708

First Posted

October 30, 2014

Last Updated

October 31, 2014

Sponsor

Seoul National University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02281708

Brief Title

Multicenter Randomized Controlled Trial Adjuvant Chemotherapy vs Observation in pStage Ib Lung Adenocarcinoma

Official Title

A Multi-center Phase III Randomized Controlled Trial Comparing Between Adjuvant Chemotherapy and Observation in High Risk Patients With Completely Resected Stage Ib Lung Adenocarcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

October 2014

Overall Recruitment Status

Unknown status

Study Start Date

October 2014 (undefined)

Primary Completion Date

September 2018 (Anticipated)

Study Completion Date

September 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Seoul National University Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Researchers developed the nomogram which evaluate the risk of recurrence after surgical resection, and found that the stage 1 NSCLC patients with more than 104 point of nomogram showed similar recurrence rate to the recurrence rate of stage 2 NSCLC patients. Thus those stage 1 NSCLC patients at high recurrence rate are considered to show positive effect of adjuvant chemotherapy and perform the study to prove this hypothesis. Applying the nomogram, the patient scored lower than 104 is categorized into low risk group and is to be grouped as the observation group which adjuvant chemotherapy will not be given. The high risk group patients (the nomogram scored larger than 104) are randomly divided into the treatment group and the observation group. Then, the clinical result on the recurrence between the observation group and the treatment group will be compared. - Regimen of the adjuvant chemotherapy: The most commonly used 1st line chemotherapy regimen which is vinorelbine plus cisplatin will be admitted for 4 cycles. Also the three days before and the after the estimated day are permitted as allowance. Intravenous administration of vinorelbine (25mg/m2), the 1st and the 8th day of the each cycle, every 3 weeks. Intravenous administration of cisplatin (75mg/m2), the 1st day of the each cycle, every 3 weeks.

Detailed Description

Enrolled stage 1B adenocarcinoma patient will be registered for the study and be randomly allocated to the treatment group and the observation group by the stratification factor; the institution. Each group is determined to have same number of study population. This study is open labeled and follow the permuted block design. Also the patients will be allocated by randomized table provided by a statistician. If it is converted to e-CRF, randomization of the patients will be performed by the automated computer program. Total 1012 patients will be enrolled to this study. Among 506 high risk stage 1B adenocarcinoma patients, patients will be allocated to the treatment and the observation groups, 253 patients each. Also 506 low risk stage 1B adenocarcinoma patients will be enrolled as the observation group. Because, among stage 1B patients, it was revealed that the high risk patients whose nomogram point exceeds 104 occupied about 50% in analysis. Estimated 3 year disease free survival for the treatment group and the observation group is 66% and 54%, respectively. The 3 year disease free survival rate for the observation group was estimated based on retrospective multicenter study on 1132 stage 1 NSCLC patients, previously reported in Korea. During the 3 year of follow up duration, the withdrawal rate was presumed to be 10% because of loss of follow-up, violation of the consent and other causes. Study population enrollment is estimated as 48 months and mean follow-up duration is estimated as 24 months. Total duration of the study is set as 72 months. In this study design, the number of the high risk patients of each group is 253 and it supports 80% power of test with a two-sided alpha level of 0.05.

6. Conditions and Keywords

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

Stage Ib Lung Carcinoma

Keywords

normogram, recurrence, adjuvant chemotherapy, disease free survival, Quality of life

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1012 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

low risk

Arm Type

No Intervention

Arm Description

low risk; observation

Arm Title

high risk; observation group

Arm Type

No Intervention

Arm Description

high risk: observation

Arm Title

high risk; adjuvant chemotherapy group

Arm Type

Experimental

Arm Description

high risk. vinorelbine plus cisplatin

Intervention Type

Drug

Intervention Name(s)

vinorelbine plus cisplatin

Other Intervention Name(s)

Navelbine (cisplatin) plus DDP

Intervention Description

Drugs will be administered for 4 cycles, and should be administered at scheduled day +/- 3 days vinorelbine 25mg/m2 IV (Day 1, 8) q 3wks cisplatin 75mg/m2 IV (Day 1) q 3wks

Primary Outcome Measure Information:

Title

disease-free survival (DFS)

Description

the time between the operation and the date of treatment for recurred lung cancer or suspected recurrence

Time Frame

3 year

Secondary Outcome Measure Information:

Title

overall survival rate (OS)

Description

the time between the operation and death from any cause

Time Frame

3 year, 5 year

Title

quality-of-life (QoL)

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must meet ALL of the following criteria in order to be eligible for this study Age ≥18 years and Age <80 Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. The pathological stage Ib adenocarcinoma after complete resection (AJCC 7th). (Patients with adenocarcinoma in situ are excluded) Patients must have undergone pulmonary resection more than lobectomy (lobectomy, bilobectomy, pneumonectomy). Patients must have undergone either mediastinal lymph node dissection or systemic sampling. Tumor must be resected completely without gross or microscopic residual tumor. The interval between surgery for lung cancer and randomization must be no more than 8 weeks. The patients must be willing and sign informed consent prior to randomization. Patients with appropriate bone marrow function. ANC ≥1,500/uL, hemoglobin ≥9.0g/dL (can be corrected by transfusion). platelet ≥100,000/uL Patients with appropriate renal function Serum creatinine ≤ 1 x UNL(upper limit or normal) or Estimated creatinine clearance ≥ 45 ml/min Patients with appropriate liver function Serum bilirubin ≤ 1.5 x UNL, AST (SGOT) and ALT (SGPT) ≤ 3 x UNL, alkaline phosphatase ≤ 3 x UNL Exclusion Criteria: Patients meeting any ONE of the following criteria are not eligible for this study. Other concurrent serious diseases that may interfere with planned treatment. Pregnant of lactation women Women of childbearing potential without a negative pregnant test (urine HCG), within 14 days prior to randomization or less than one year after menopause. Any previous systemic chemotherapy for cancer or anti-cancer immunotherapy. History of non-lung malignancies within the 5 years prior to study entry, except for the following: carcinoma in situ of the cervix, melanoma in situ. Serious cardiac illness or medical conditions including uncontrolled hypertension, myocardial infarction within 6 months, unstable angina pectoris, heart failure >NYHA grad II, or uncontrolled arrhythmia. Patients with sensitivity to vinorelbine or cisplatin. Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sanghoon Jheon, Ph.D.

Phone

82317877140

jheon@snubh.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sanghoon Jheon, Ph.D.

Organizational Affiliation

Seoul National Univsersity Bundang Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Seoul National University Bundang Hospital

City

Seongnam-si

State/Province

Gyeonggi-do

ZIP/Postal Code

463-707

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sanghoon Jheon, Ph.D.

Phone

82317877140

jheon@snubh.org

12. IPD Sharing Statement

Citations:

PubMed Identifier

23532112

Citation

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Results Reference

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PubMed Identifier

21440264

Citation

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Results Reference

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PubMed Identifier

19211260

Citation

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PubMed Identifier

18809614

Citation

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Results Reference

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PubMed Identifier

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Citation

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Results Reference

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Citation

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Results Reference

result

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Multicenter Randomized Controlled Trial Adjuvant Chemotherapy vs Observation in pStage Ib Lung Adenocarcinoma

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