JCOG2108: A multicenter randomized phase III study of systemic chemotherapy followed by maintenance therapy versus local consolidation therapy for postoperative oligometastatic recurrent non-small cell lung cancer

JRCT ID: jRCTs031230475

Registered date:24/11/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Non-small cell lung cancere
• Date of first enrollment: 24/11/2023
• Target sample size: 200
• Study type: Interventional

Intervention(s)

Group A: Systemic therapy + Maintenance therapy
Group B: Systemic therapy + Local therapy

Outcome(s)

• Primary Outcome: Overall Survival
• Secondary Outcome: Progression-free survival, Progression lesions (oligometastases, non-oligometastases), Oligometastases-free survival by type of local therapy, Adverse event rate, Severe adverse event rate, Quality of life (FACT-TOI, EQ-5D-5L )

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Criteria for the primary registration
(1) Histologically completely resected non-small cell lung cancer.
(2) One hundred and eighty days or more have passed since the initial lung resection.
(3) The initial pathological stage was I to III non-small cell lung cancer.
(4) If there is a history of postoperative adjuvant chemotherapy, including immune checkpoint inhibitors such as anti-PD-1 antibodies, anti-PD-L1 antibodies, and anti-CTLA-4 antibodies, 180 days or more have passed since the last administration of postoperative adjuvant chemotherapy. The conditions is not applicable to UFT therapy.
(5) All of the examinations including contrast-enhanced neck to pelvic CT (*1), FDG-PET (or PET/CT), and contrast-enhanced brain MRI (*2) should fulfill all of the following criteria for oligometastases:
*1 If the use of contrast media is not possible due to the allergy, renal dysfunction, or bronchial asthma, unenhanced CT is acceptable.
*2 If the use of contrast media is not possible due to the allergy, renal dysfunction, or bronchial asthma, unenhanced MRI is permissible. If MRI is not possible due to a pacemaker or claustrophobia, evaluation by CT is permissible.
a) The number of metastases is three or less. Lymph node metastases count as one metastasis per lymph node and are included in the number of metastatic organs.
b) No local recurrence (*3), regardless of the number of metastases.
*3 This study defines local recurrence as recurrence at the resection margin, including the bronchial stump, the hilar and mediastinal lymph nodes on the ipsilateral side as the primary lesion, the hilar and mediastinal lymph nodes on the contralateral side, the intrapulmonary lymph nodes on the ipsilateral side, malignant pleural effusion on the ipsilateral side, and disseminations on the ipsilateral
c) If the number of metastasis is one, it should not be limited to one lung nodule.
d) Regardless of the number of metastases, the metastases are not limited to the brain only,
e) All of the following criteria are met for bone metastasis.
- Not metastasis to three consecutive vertebral bodies.
- Not vertebral metastasis (Bilsky grade 1b or higher) that shows progression into the spinal canal.
- Not long bone metastasis.
- Does not have severe pain that is poorly controlled by medication.
f) All of the following criterial are met for brain metastasis.
- The largest tumor diameter is 3cm or less and asymptomatic.
- If there are multiple brain metastases, the total of the the largest tumor diameter is 5 cm or less.
(6) All metastatic lesions can be treated by local therapies as determined by the participating institution's surgeon or radiotherapist.
(7) In non-squamous cell carcinoma, EGFR gene driver mutations (exon 19 deletion, L858R, G719X, L861Q, S7681, and these mutations with T190M mutation) and ALK immunostaining/ALK fusion genes are negative (EGFR gene teting and ALK immunostaining/ALK fusion gene are not mandatory in squamous cell carcinoma).
(8) ROS1 fusion gene, BRAF (V600E) gene mutation, MET exon 14 skipping mutation, RET fusion gene, and NTRK fusion gene are negative or unknown.
(9) The age on the primary registration is 18 or older.
(10) Performance status (PS) is 0 or 1 according to ECOG criteria (PS must always be recorded in the medical record).
(11) No history of systemic chemotherapy for metastasis lesions, excluding preoperative and postoperative adjuvant chemotherapy.
(12) The latest values within 14 days before the primary resistrartion meet all of the following.
a) Neutrophils >= 1,500/mm3
b) Hemoglobine >= 9.0 g/dL (no blood transfusion has been performed within 14 days before the blood collection used for the registration)
c) Platelet count >= 100,000/mm3
d) Total bilirubin <= 1.5 mg/dL
e) AST <= 100 U/L(If there is liver metastasis, AST <= 200 U/L)
f) ALT <= 100 U/L(If there is liver metastasis, ALT<= 200 U/L)
g) Serum creatinine <= 1.5 mg/dL
h) SpO2 >= 92% under room air (SpO2 must always be recorded in the medical record)
(13) Written informed consent has been obtained from the patient to participate in the study.

Criteria for the secondary registration
(1) Primary registration was performed, and 4 courses (1 couse = 3 weeks) of induction therapy have been performed ( even if the administration on day 8 and day 15 or day 15 of the fourth course is skipped), or the induction therapy is terminated at the third courses due to adverse events).
(2) No apparent increase in size(*) in any of metastases or new distatnt metastasis are observed.
* An apparent increase is considered to be when the long diameter of any lesion is increased by more than 10% and more than 5 mm compared to the diameter before treatment. However, lymph nodes are evaluated by their short diameter.
(3) The secondary registration date is within 28 days (4 weeks) of the response evaluation of induction therapy (if there are multiple image modalityes used for the evaluation, the date of the latest examination is adopted).
(4) Within 64 days (9 weeks) to 182 days (26 weeks) after primary registration.
(5) No metastatic site larger than 3 cm in tumor diameter.
(6) If brain metastases are found at the time of primary registration, radical local therapy (stereotactic irradiation or stereotactic radiotherapy) has been performed.
(7) Al least one oligometastasis that canbe treated locally remains. However, brain lesions where radical local therapy has been performed are not included.
(8) All metastatic lesions can be treated by local therapies as determined by the participating institution's surgeon or radiotherapist.
(9) PS is 0 or 1 according to ECOG criteria (PS must always be recorded in the medical record).
(10) The latest values within 14 days before the secondary resistrartion meet all of the following.
a) Neutrophils >= 1,500/mm3
b) Hemoglobine >= 9.0 g/dL (no blood transfusion has been performed within 14 days before the blood collection used for the registration)
c) Platelet count >= 100,000/mm3
d) Total bilirubin <= 1.5 mg/dL
e) AST <= 100 U/L(If thereis liver metastasis, AST <= 200 U/L)
f) ALT <= 100 U/L(If thereis liver metastasis, ALT<=200 U/L)
g) Serum creatinine <= 1.5 mg/dL
h) SpO2 >= 92% under room air (SpO2 must always be recorded in the medical record)

Exclude criteria

(1) Simultaneous or metachronous (within 2 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 a continuous systemic administration (oral or intravenous) of steroids exceeding 10 mg/day in predonisolone equivalents, or other immunosuppressive drugs.
(7) Uncontrollable diabetes mellitus.
(8) History of unstable angina pectoris within three weeks or myocardial infarction within six months before registration.
(9) Have an uncontrolled valvular disease, dilated cardiomyopathy, hypertrophic cardiomyopathy.
(10) One or a combination of the following conditions diagnosed via chest CT scan: interstitial pneumonia, severe pulmonary fibrosis, or seveare emphysema.
(11) Positive HBs antigen and/or HCV antibody.

Related Information

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