S-1 and cisplatin with radiotherapy followed by durvalumab for locally advanced lung cancer

JRCT ID: jRCTs031190127

Registered date:01/11/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Lung cancer
• Date of first enrollment: 16/12/2019
• Target sample size: 58
• Study type: Interventional

Intervention(s)

[S-1 and cisplatin with concurrent thoracic radiotherapy]
Radiotherapy: 60 Gy / 30 fr, 5 times a week
Chemotherapy: 1 course 28 days x 2 coursesCDDP (60 mg / m2, Day 1) IV infusion
S-1 (80-120 mg, Day 1-14) Oral, Day 15-28 withdrawal
In addition, administration of S-1 ends with radiation treatment end date

[Maintenance therapy] Start within 42 days after the end of radiation treatment.
Durvalumab (10 mg / kg) every 2 weeks for up to 12 months

Outcome(s)

• Primary Outcome: 1 year progression free survival rate

Secondary Outcome

Progression free survival (PFS)
Response rate (ORR)
18-month overall survival
Safety and adverse event profile (based on CTCAE, ver. 5.0)
Chemotherapy completion rate, radiation therapy completion rate, chemoradiotherapy completion rate
Durvalumab maintenance therapy transfer rate
PFS from the start of maintenance therapy

Key inclusion & exclusion criteria

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

Include criteria

Primary registration
1. Informed consent is given to the patients themselves before the start of the study, and written consent has been obtained
2. Men and women aged 20 and over at the start of treatment
3. Non-small cell lung cancer diagnosed with histopathology or cytology (not including small cell carcinoma), unresectable locally advanced stage lung cancer (Stage IIIA / IIIB / IIIC) (IASLC staging manual in Thoracic Oncology, According to Version 8th)
4. Patients with measurable lesions based on RECIST ver. 1.1
5. No previous history of chemotherapy (including molecular targeted drugs, immune checkpoint inhibitors) and chest radiation therapy, including treatment for other carcinomas.
6. 12 weeks or more expected to survive
7. ECOG Performance Status 0-1
8. Maintaining organ function and bone marrow function as follows (latest examination value within 14 days of registration)
Neutrophil count > 1500 / mm3
Platelet count > 100,000 / mm3
Hemoglobin > 9.0 g / dL
Serum creatinine <= 1.5 mg / dL or creatinine clearance> 50 mL / min (by the Cockcroft-Gault formula)
Bilirubin <= 1.5 x upper limit of normal (ULN)
AST and ALT <= 2.5 x ULN
SpO2 >= 92% or PaO2 >= 70 Torr (room air)
9. Possibility of radical concurrent chemoradiotherapy (V20 <= 35%)
10. Postmenopausal condition can be confirmed, or in premenopausal women, pregnancy test with urine or serum is negative
11. In female patients who may be pregnant and in male patients who have female partners who may be able to give birth, both men and women have intention of contraception

Secondary registration
1. Explain to the patient that he / she is going to the maintenance therapy before the maintenance therapy, can confirm the intention for the maintenance therapy, and can also confirm from the medical record
2. Non-PD for induction therapy (chemoradiotherapy)
3. ECOG Performance Status 0-1
4. Maintaining organ function and bone marrow function as shown below
Neutrophil count> 1500 / mm3
Platelet count> 100,000 / mm3
Hemoglobin >9.0 g / dL
Serum creatinine <= 1.5 mg / dL or creatinine clearance> 50 mL / min (by the Cockcroft-Gault formula)
Bilirubin <= 1.5 x ULN
AST and ALT <= 2.5 x ULN
SpO2 > 92% or PaO 2> 70 Torr (room air)

Exclude criteria

Primary registration
1. Patients with interstitial pneumonia or pulmonary fibrosis evident on chest CT
2. Patients with a history of serious allergies or hypersensitivity to therapeutic agents
3. Patients who are medically contraindicated for therapeutic agents
4. Patients who have a history of allogeneic organ transplantation
5. Patients who have used immunotherapy or investigational drug within 4 weeks of starting treatment (monoclonal antibody within 6 weeks)
6. Patients with active or previous autoimmune disease , or patients with active inflammatory disease (inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), colonic diverticulitis, SLE, sarcoidosis, polyangiitis granulomatosis, Graves' disease, rheumatoid arthritis, hypophysitis, grape (With a history of less than 2 years), or patients with a coexistence / history of primary immunodeficiency. However, registration is permitted if
Patients with vitiligo or alopecia
Stable hypothyroidism during hormone replacement therapy (eg Hashimoto's disease)
All chronic skin diseases that do not require systemic therapy
Patients who have not been active in the past 5 years will be allowed to register,Limited to later registration
Celiac disease patients controlled only by diet therapy
7. Patients with active or infectious diseases being treated
8. Patients with a mixture of small cell lung cancer and non-small cell lung cancer
9. Patients who use a therapeutic agent that has an immunosuppressive effect within 28 days from the start of study treatment (excluding systemic steroid treatment with nasal or inhaled steroids, or equivalent to 10 mg/ day or less in terms of prednisolone)
10. Patients who have had surgery within 4 weeks prior to enrollment
11. Patients with SVC syndrome that has difficulty in high-volume infusion, symptomatic heart failure, arrhythmia requiring hospitalization,uncontrolled hypertension, unstable angina, active peptic ulcer, mental disease patients who have difficulty in maintaining treatment compliance
12. Patients with hepatitis B merger (positive for HBs antigen), HCV antibody positive patients (registration is allowed if the polymerase chain reaction of HCV RNA is negative)
13. Patients with a history of malignancy within 5 years of treatment (excluding basal cell carcinoma of the skin and CIS in the cervix)
14. Patients who have used attenuated live vaccination within 30 days of study registration
15. Patients who have no intention of contraception during the treatment period and at least 90 days after the end of treatment
16. Patients who are willing to donate blood during the treatment period and at least 90 days after the end of treatment
17. Pregnant or breast feeding patients
18. Patients judged to be ineligible by the investigator

Secondary registration
1. Patients who had grade 2 or more radiation pneumonitis by the time of secondary registration
2. Patients with uncontrolled disease or active or treating infections
3. Patients who use a therapeutic agent that has an immunosuppressive effect within 28 days from the start of study treatment (excluding nasal or inhaled steroids, or systemic steroid treatment equivalent to 10 mg / day or less in terms of prednisolone conversion) However, chemoradiation The administration of steroids as antiemetics in treatment is acceptable.
4. Patients with unrecovered Grade 2 or higher toxicity in induction chemotherapy chemoradiotherapy, excluding test values defined in alopecia, vitiligo, and selection criteria
For patients with Grade 2 or higher neuropathy, whether or not to register is determined by discussion between the secretariat and the steering committee.
For patients with irreversible toxicity that is not expected to be aggravated by Durvalumab maintenance therapy, determine whether or not to register by consultation between the secretariat and the steering committee.
5. Patients judged to be ineligible by the investigator

Related Information

• Primary Sponsor: Tanzawa Shigeru
• Source(s) of Monetary Support: AstraZeneca K.K. Externally sponsored scientific research