JCOG1905: A randomized controlled phase III trial on continued or paused PD-1 pathway blockade for patients with advanced renal cell carcinoma

JRCT ID: jRCT1031200071

Registered date:20/07/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: advanced renal cell carcinoma
• Date of first enrollment: 10/09/2020
• Target sample size: 250
• Study type: Interventional

Intervention(s)

Arm A (Standard arm): Continue the treatment including PD-1 pathway inhibitor treated before enrollment.
Arm B (Test arm): Discontinue the PD-1 pathway inhibitor monotherapy treated before enrollment.

Outcome(s)

• Primary Outcome: overall survival
• Secondary Outcome: progression free survival, time to failure of strategy, adverse event rate , severe adverse event rate,Response rate of PD-1 pathway inhibitor resumption(Arm B), progression free survival of PD-1 pathway inhibitor resumption(Arm B)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Histologically proven as clear cell renal carcinoma by primary or metastatic tumor.
(2) Diagnosed as advanced (unresectable or metastatic) renal cell carcinoma before starting PD-1 pathway inhibitor.
(3) Aged 20 years and older.
(4) ECOG Performance status 0 or 1.
(5) One of the following <1> to <6>:
<1>Patients who received nivolumab plus ipilimumab as first-line treatment meet all of the following:
(i) No concurrent anticancer drug other than nivolumab at the time of registration.
(ii) Cumulative dose of nivolumab of 1,680 mg/body or more within 36 weeks (252 days) before registration, or 2,400 mg/body or more for 36 to 48 weeks (336 days) before registration.
Nivolumab 240 mg / body was administered 7 times or more.
(iii) More than 24 weeks (168 days) and less than 48 weeks (336 days) after starting nivolumab.
(iv) Nivolumab has been administered at least once within 4 weeks (28 days) before registration.
<2>Patients who received pembrolizumab plus axitinib as first-line treatment meet all of the following:
(i) No concurrent anticancer drug other than pembrolizumab or axitinib at the time of registration.
(ii) Cumulative dose of pembrolizumab of 1,000 mg/body or more within 36 weeks (252 days) before registration, or 1,400 mg/body or more for 36 to 48 weeks (336 days) before registration.
(iii) More than 24 weeks (168 days) and less than 48 weeks (336 days) after starting pembrolizumab.
(iv) Pembrolizumab has been administered at least once within 4 weeks (28 days) before registration.
<3>Patients who received abelumab plus axitinib as first-line treatment meet all of the following:
(i) No concurrent anticancer drug other than pembrolizumab or axitinib at the time of registration.
(ii) Abelumab 10 mg/kg was administered at least 7 times within 36 weeks (252 days) before registration, or at least 10 times for 36 to 48 weeks (336 days) before registration.
(iii) More than 24 weeks (168 days) and less than 48 weeks (336 days) after starting abelumab.
(iv) Abelumab has been administered at least once within 4 weeks (28 days) before registration.
<4>Patients who received nivolumab plus cabozantinib as first-line treatment meet all of the following:
(i) No concurrent anticancer drug other than nivolumab or cabozantinib at the time of registration.
(ii) Nivolumab 10 mg/kg was administered at least 7 times within 36 weeks (252 days) before registration, or at least 10 times for 36 to 48 weeks (336days) before registration.
(iii) More than 24 weeks (168 days) and less than 48 weeks (336 days) after starting nivolumab.
(iv) Nivolumab has been administered at least once within 4 weeks (28 days) before registration.
<5>Patients who received pembrolizumab plus lenvatinib as first-line treatment meet all of the following:
(i) No concurrent anticancer drug other than pembrolizumab or lenvatinib at the time of registration.
(ii) Cumulative dose of pembrolizumab of 1,000 mg/body or more within 36 weeks (252 days) before registration, or 1,400 mg/body or more for 36 to 48 weeks (336 days) before registration.
(iii) More than 24 weeks (168 days) and less than 48 weeks (336 days) after starting pembrolizumab.
(iv) Pembrolizumab has been administered at least once within 4 weeks (28 days) before registration.
<6>Patients who received nivolumab since second-line treatment meet all of the following:
(i) No concurrent anticancer drug other than nivolumab at the time of registration.
(ii) Cumulative dose of nivolumab of 1,680 mg/body or more within 36 weeks (252 days) before registration, or 2,400 mg/body or more for 36 to 48 weeks (336 days) before registration.
(iii) More than 24 weeks (168 days) and less than 48 weeks (336 days) after starting nivolumab.
(iv) Nivolumab has been administered at least once within 4 weeks (28 days) before registration.
(6) If nephrectomy or metastatic resection is performed before registration, some lesions remain after surgery. Lesions that disappear on the image due to administration of the PD-1 pathway inhibitor also regards as remaining lesions.
(7) measurable lesions does not matter.
(8) All lesions within 4 weeks (28 days) before registration are showed a tendency to shrink compared with the start of PD-1 pathway inhibitor administration.
(9) No previous history of chemotherapy, radiation therapy, hormonal therapy, or targeted drugs for other cancer.
(10) No history of autoimmune disease.
(11) No symptomatic brain metastases, meningeal carcinomatosis, spinal metastases requiring radiotherapy or surgery.
(12) No Grade >=3 adverse events attributable to PD-1 pathway inhibitor at registration..
(13) Adequate function of major organs.
(14) Written informed consent.

Exclude criteria

(1) Synchronous or metachronous (within 5 years) malignancies.
(2) Infectious disease requiring systemic treatment.
(3) Pyrexia of 38 or higher degrees centigrade.
(4) Female during pregnancy, within 28 days of postparturition, or during lactation and male expecting partner's pregnancy.
(5) Severe psychological disorders.
(6) Patients receiving systemic steroids, other immunosuppressive drugs, or immunoglobulin at a dose of more than 15 mg / day of prednisolone for diseases other than autoimmune diseases.
(7) Poorly controlled diabetes mellitus.
(8) Poorly controlled hypertension.
(9) History of unstable angina pectoris with new onset or exacerbation within recent 3 weeks or myocardial infarction within 6 months before registration.
(10) Positive HBs antigen
(11)Severe emphysema, interstitial pneumonia or pulmonary fibrosis based on chest CT.

Related Information

• Primary Sponsor: MATSUMOTO Takashi
• Secondary Sponsor: ETO Masatoshi
• Source(s) of Monetary Support: National Cancer Center Japan,Japan Agency for Medical Research and Development,National Federation of Health Insurance Societies