Clinical trial NCT03380468: Adjuvant Chemotherapy for High Risk Stage I Lung Adenocarcinoma
Official title: Adjuvant Chemotherapy Versus Observation in Fully Resected Stage I Lung Adenocarcinoma With High Risk of Post-operative Recurrence
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Lung Neoplasms
Keywords: Lung adenocarcinoma
adjuvant chemotherapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2017-12-21
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a clinical trial from Eastern Cooperative Thoracic Oncology Project (ECTOP), numbered as ECTOP-1004. Solid subtype, micropapillary subtype, vascular involvement, pleural involvement and low differentiation are high risk factors of post-operative recurrence for early-stage lung adenocarcinoma patients. The purpose of this clinical trial is to determine whether the widely used adjuvant chemotherapy strategy cisplatin/ pemetrexed is more effective than no further treatment for Stage pI lung adenocarcinoma patients with high post-operative recurrence risk - in terms of no dose related toxicities, premature treatment withdrawal or death.

Detailed description: Background:

Management of lung cancer varies according to the clinical and pathological stage. For stage I lung adenocarcinoma, radical surgery is the preferred initial treatment and adjuvant chemotherapy is usually not recommended due to a fine prognosis and relatively low post-operative recurrence rate. Still, a number of stage pI patients will suffer a relapse after surgery, among which are highly associated with solid subtype, micropapillary subtype, vascular involvement, pleural involvement and low differentiation. Recently, some retrospective researches have shown a significant survival benefit of adjuvant chemotherapy for such stage pI high-recurrent-risk patients, but there lacks evidence from prospective randomized clinical trails.

Objective:

1. Major: to compare disease free survival and over all survival of fully resected stage pI high-recurrent-risk patients from both arms (adjuvant chemotherapy vs. observation)
2. To assess the safety and efficacy of chemotherapy regimen cisplatin plus pemetrexed to fully resected stage pI high-recurrent-risk patients.
3. To collect clinical pathological characteristics and prognosis information of stage pI patients with solid subtype, micropapillary subtype, vascular involvement, pleural involvement and low differentiation.
4. To determine the association among age, gender, smoking history, pathological subtypes, histological differentiation, pleural involvement, vascular involvement and driving mutations.

Randomization:

Each of the patients enrolled will be recorded in the computer system. Blank randomization will be done using a digital randomization software, at least 1 week before the first time of chemotherapy or observation.

Prechemotherapy assessment: For all the patients enrolled, the postoperative physical or laboratory examination should be equally qualified no matter which group they will be in. For Group Adjuvant Chemotherapy patients, they will receive laboratory examinations before chemotherapy to test blood cells and liver function in consideration of safety as routine.

Follow up:

Patients will be followed up per 4 months for the first three years and each six months for the forth to fifth years during the research. Lung multi-detector row computed tomography (MDCT) and abdominal ultrasonography tests will be done twice a year; bone SPECT scan and enhanced brain MRI scan will be conducted per year routinely. Patients will be suggested to continue the annual follow-up after the research.

Main research variables:

Primary end point: Disease free survival in the two arms

Secondary endpoints:

1. Overall survival
2. Recurrence pattern: Locoregional recurrence, metastatic recurrence, or both
3. Quality of life: assessed with Eastern Cooperative Oncology Group- quality of life questionnaire(EORTC QLQ-C30/- LC13) scale.

This study is recognized in our institute as "Eastern Cooperative Thoracic Oncology Projects (ECTOP-1004)"

Eligibility criteria: Inclusion Criteria:

1. Stage pI lung adenocarcinoma confirmed through formalin-fixed paraffin-embedded tumor tissue, complete resection with mediastinal lymph node dissection
2. Meet one of following conditions: a, Solid predominant adenocarcinomas; b, micropapillary predominant adenocarcinoma; c, low differentiation, unable to identify histological subtypes; d, pleural involvement; e, vascular involvement with solid subtype component or micropapillary component.
3. Aged 18-70 years old.
4. Eastern Cooperative Oncology Group score standard (ECOG) status 0-1.
5. Medical condition permits adjuvant chemotherapy.
6. Patients accept the clinical trial protocol and Informed Consent Form (ICF) signed.

Exclusion Criteria:

1. Concurrent other malignancies
2. Prior chemotherapy and/or radiation therapy for lung cancer
3. Central type lung cancer
4. Concurrent other unresected suspicious nodules or masses in lung
5. Medical condition that will not permit treatment or follow up according to the protocol, or ECOG status \>1.
6. Pregnant or nursing women.

Primary outcomes:
measure: Recurrence free survival (RFS)
timeFrame: up to 5 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: up to 5 years
Other outcomes:
measure: Recurrence pattern
timeFrame: up to 5 years
measure: Quality of life
timeFrame: up to 5 years
Locations:
city: Shanghai
country: China
facility: Fudan University Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Haiquan Chen, MD
role: PRINCIPAL_INVESTIGATOR
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