JCOG2103: Randomized phase III study comparing systemic therapy and debulking surgery consisting of primary tumor resection with systemic therapy alone for clinical stage IVA (cT1-2bN0-1M1a) non-small cell lung cancer with radiologically undetermined pleural dissemination

JRCT ID: jRCTs031220666

Registered date:28/02/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: non-small-cell lung cancer
• Date of first enrollment: 28/03/2023
• Target sample size: 170
• Study type: Interventional

Intervention(s)

Group A: Standard of care drug therapy (SoC)
Group B: Standard of care drug therapy (SoC) + Surgery

Outcome(s)

• Primary Outcome: Overall survival
• Secondary Outcome: Progression-free survival, Local progression-free survival, Distant progression-free survival, Response rate, Adverse event rate, Serious adverse event rate, Cumulative incidence of pleural effusion (Grade 2 or higher) rate, Quality of life (EQ-5D, FACT-L)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 79age old
• Gender: Both

Include criteria

Primary registration criteria
(1) Pathologically diagnosed as non-small cell lung cancer by any of the following
(i) Histological or cytological diagnosis of the primary tumor
(ii) Histological diagnosis of pleural disseminatio
(2) Histological diagnosis of pleural dissemination lesion by thoracoscopic or open chest biopsy (positive pleural fluid cytology alone is not acceptable).
(3) The patient has cT1a-2bN0-1M1a clinical stage IVA (UICC TNM classification, 8th edition) with all of the following criteria (i) to (viii) on chest contrast CT, thin slice CT, brain contrast CT or MRI, or PET/CT.
(i) No pleural dissemination lesion is detected on thin slice CT, or a pleural dissemination lesion is present but not measurable (maximum diameter less than 10 mm).
(ii) PET/CT shows no apparent abnormal accumulation of FDG in the pleura suspicious for pleural dissemination.
(iii) No additional tumor nodule in the contralateral lung.
(iv) No Grade 2 or higher pleural effusion
(v) No nodule suspected as pericardial dissemination in the pericardium.
(vi) No evidence of pericardial effusion exceeding physiological accumulation.
(vii) No cN1 lymph node lesion with extranodal infiltration
(viii) Primary tumor and N1 lymph node (in case of cN1) are considered completely resectable by partial resection, segmental resection, or lobectomy.
(4) confirmed EGFR gene mutations or ALK translocation status for non-squamous cell carcinoma.
(5) Over 18 years old and under 79 years old.
(6) Performance status 0 or1
(7) No prior thoracic surgery
(8) No history of chemotherapy for lung cancer
(9) No history of radiation therapy with mediastinum or hil um for other cancer types. No history of Grade 2 or higher radiation pneumonitis
(10) No complication of autoimmune disease or a history of chronic or recurrent autoimmune disease.
(11) No interstitial pneumonitis, pulmonary fibrosis, nor severe emphysema on chest CT.
(12) Predicted residual volume per second after resection is greater than 800 mL.
(13) Adequate function of major organs.
(14) Written informed consent.

Secondary registration selection criteria
(1) Primary registration was performed.
(Driver gene mutation positive) Three courses of standard of care drug therapy (SoC) was completed
(Driver gene mutation negative) Four courses of SoC was completed or only three courses is completed due to adverse events.
(2) Following (i)-(ii) is satisfied.
(i) Contrast-enhanced CT after last courses of SoC does not show obvious progressions compared to CT before primary registration.
(ii) No obvious progressions from the start of SoC .
(3)
(Driver gene mutation positive)
Within 56 days from the start of the final course of SoC.
(Driver gene mutation positive)
Within 48 days from the start of the final course of SoC.
(4) Secondary registration is within 14 days of the response evaluation
(5) Within 57-182 days from the primary registration.
(6) Primary tumor are considered completely resectable
(7) Predicted residual volume per second after resection is greater than 800 mL.
(8) Adequate function of major organs.

Exclude criteria

(1) Simultaneous or metachronous (within 5 years) double cancers , with the exception of intramucosal tumor curable with local therapy.
(2) Active infection requiring systemic therapy.
(3) Fever over 38 degrees Celsius
(4) Female during pregnancy, within 28 days of postparturition, or during lactation. Male who wants partner's pregnancy.
(5) Psychological disorder difficult to participate in this clinical study.
(6) Receiving continuous systemic corticosteroid or immunosuppressant treatment.
(7) Uncontrollable diabetes mellitus.
(8) Uncontrollable hypertension.
(9) History of unstable angina pectoris within three weeks or myocardial infarction within six months before registration.
(10) Have an uncontrolled valvular disease, dilated cardiomyopathy, hypertrophic cardiomyopathy.
(11) Positive HBs antigen, HBC angigen or HIV antigen.

Related Information

• Primary Sponsor: WATANABE Shun-ichi
• Source(s) of Monetary Support: National Cancer Center Japan