Combination of checkpoint inhibitor and radiotherapy for re-current gastric cancer after initial treatment with standard therapy.

JRCT ID: jRCTs021180002

Registered date:10/12/2018

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Gastric cancer
• Date of first enrollment: 28/03/2018
• Target sample size: 40
• Study type: Interventional

Intervention(s)

Radiotherapy before administration of nivolumab
Dose: 22.5 Gy/5 fractions/5 days
Nivolumab: 3 mg/kg or 240 mg/body,
every 2 weeks to a total of 6 courses

Outcome(s)

• Primary Outcome: Disease control rate

Secondary Outcome

1) Median survival time
2) Safety
3) Local control rate
Ancillary analysis: Immunologic parameters

Key inclusion & exclusion criteria

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

Include criteria

1) Unresectable recurrent gastric cancer with progression (intolerance or PD) after standard treatment (primary and secondary chemotherapy).
2) More than one measurable lesion defined by RECIST guideline version 1.1 in diagnostic imaging (chest-abdomen-pelvis contrast-enhanced CT or PET-CT) within 14 days before entry, with at least one lesion >= 2 cm.
3) Age: >= 20 years-old
4) ECOG performance status (PS): 0-2
5) No contraindication for nivolumab (anti-PD-1 antibody) administration.
6) No contraindication for radiotherapy.
7) The most recent laboratory results within 14 days before study entry fulfill the following. However, if the laboratory results for study entry do not fall within 7 days before the first administration of nivolumab, the blood test must be performed again within 7 days before the administration to check if the results fulfill the following. The use of G-CSF or blood transfusion within 14 days before the laboratory testing is not allowed.
WBC >= 3000/micro liter (ul), neutrophil >= 1500/ul, hemoglobin >= 9.0g/dl, platelets >= 100,000/ul, total bilirubin <= 2.0 times the institutional standard upper limit (ISUL), AST (GOT) and ALT (GPT) <= 3.0 times ISUL (in case with liver metastasis, <= 5.0 times ISUL), serum creatinine <= 1.5 times ISUL or creatinine clearance >= 60 ml/min calculated with cockcroft-Gault equation.
Male Ccr = [(140-age)*body weight(kg)]/[72*serum creatinine(mg/dl)]
Female Ccr = 0.85*[(140-age)*body weight(kg)]/[72*serum creatinine(mg/dl)]
8) Expected survival >= 3 months.
9) Written informed consent obtained before entry to the study.

Exclude criteria

1) No tumor lesions to be irradiated.
2) History of other cancers (intraepithelial cancer of uterine cervix, fully treated basal cell carcinoma of skin, malignant tumors treated before >= 5 yrs and w/o recurrence are excluded).
3) Past severe hypersensitive reaction to antibody (Ab) drugs.
4) Use of immunosuppressant drugs or adrenocortical hormone (predonine or prednisolone (PDN/PSL) equivalent >= 15 mg/day).
5) Active autoimmune diseases or history of recurrent autoimmune diseases. Patients (Pts) with type-1 diabetes, hypothyroid controlled with hormone replacement therapy, dermatosis without need for systemic therapy (for example, vitiligo, psoriasis, alopecia) are eligible.
6) History of interstitial pneumonia or pulmonary fibrosis diagnosed with imaging studies (CT is preferred) or clinical findings.
7) Presence of severe disease or pathology.
8) Pts during pregnancy or lactation.
9) Fertile female pts w/o intention to practice contraception.
10) Fertile male pts w/o intention to practice contraception during and for 7 months after the study, if the partners are fertile females.
11) Prohibited pre-treatment.
Within 56 days before entry: radioactive drugs (exclude those intended for testing or diagnosis)
Within 28 days before entry: systemic adrenocortical hormone (excludes temporary use or PDN/PSL equivalent of <15 mg/day), immunosuppressant drugs, anti-cancer drugs, adhesive treatment of pleura or pericardium, surgery with general anesthesia, use of unapproved drugs.
Within 14 days before entry: surgery with local or superficial anesthesia.
12) Concurrent participation in other clinical trials/studies (excludes those w/o intervention).
13) Positivity in HIV Ab test, HIV Ag test, or HTLV-1 Ab test.
14) History of treatment using ONO-4538, anti-PD-1 Ab, anti-PD-L1 Ab, anti-PD-L2 Ab, anti-CD137 Ab, anti-CTLA-4 Ab, or other Ab or drugs intended for T-cell regulation.
15) Pts whom the physicians in the study consider inappropriate for entry.

Related Information

• Primary Sponsor: Kono Koji

Source(s) of Monetary Support

Ono Pharmaceutical Co.,ltd.
Bristol-Myers Squibb Company

• Secondary ID(s): UMIN000031508, NCT03453164