PhaseII study of DOCETAXEL plus RAMUCIRUMAB for NSCLC with brain metastasis

JRCT ID: jRCTs071180048

Registered date:15/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Non-small cell lung carcinoma
• Date of first enrollment: 27/10/2017
• Target sample size: 65
• Study type: Interventional
• Intervention(s): Ramucirumab plus Docetaxel

Outcome(s)

• Primary Outcome: progression free survival

Secondary Outcome

Intracracnial progression free survival
overall survival
disease control rate
overall response rate
safety

Key inclusion & exclusion criteria

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

Include criteria

1. Patients who are histologically or cytologically confirmed as non-small-cell lung cancer.
2. Patients with asymptomatic brain metastases and in which one or more metastatic brain tumors (5 mm or more) with the longest diameter of 2 times or more the slice width are confirmed by contrast-enhanced MRI, and the following conditions should be met.
(1) Patients in which stereotactic radiosurgery (SRS) such as gamma knife is performed, SRS must be completed by 2 weeks before the start date of protocol treatment.
(2) Patients with untreated brain metastases are allowed only if they are asymptomatic and the investigator determined that SRS does not need to be performed prior to chemotherapy.
3. Patients who have a history of chemotherapy of 1 or more regimens and whose exacerbations are confirmed 4 weeks after the end of prior chemotherapy, or those who have been confirmed to have exacerbations during maintenance therapy.
> Drugs for pretreatment include cytocidal anticancer drugs (platinum preparations, non-platinum preparations), EGFR-TKIs, ALK inhibitors, immune checkpoint inhibitors, angiogenesis inhibitors (Bevacizumab, etc.).
4. Performance Status(ECOG) 0-1
5. Patients are at least 20 years of age (age at informed consent).
6. Patients in which the functions of major organs such as bone marrow, liver, and kidney are maintained.
7. Patients with life expectancy of at least 3 months.
8. Patients in which the following period has passed since the prior treatment as of the start date of protocol treatment.
> Chemotherapy, immune checkpoint inhibitors: passed >=4weeks after the final administration of prior treatment
> EGFR-TKI:the next day after the last administration
> Radiation therapy: passed >= 28 days after the day of final radiation in the case to chest, and passed 7 days after the day of final radiation in the case to other than chest
> Operation/treatment (including chest drainage): passed >=4 weeks after the day of final operation/treatment
9. In the case of gestational/reproductive age, contraception can be performed by an appropriate method during the period from the administration of ramucirumab to 4 months after the final administration. In the case of women who can become pregnant, a negative pregnancy test should be confirmed at least one week before enrollment.
10. Patients with active double cancer.
11. Patients providing the written informed consent.

Exclude criteria

1. Patients without prior chemotherapy.
2. Patients who undergo surgery within 28 days before the date of informed consent, or who have intravenous device placement within 7 days. Patients schedules for surgery after the start of the study.
3. Patients in which symptomatic brain metastases, or brain metastases regardless of symptom are treated by cranial irradiation or surgery (SRS only is acceptable).
4. Patients in which meningeal dissemination has been confirmed by MRI or cerebrospinal fluid test.
5. Patients in which intratumoral bleeding of brain metastases and other bleeding of the central nervous system have been confirmed within 21 days before the date of informed consent.
6. Patients with findings suggestive of cavities in tumors inside and outside the skull and infiltration into large blood vessels.
7. Patients with uncontrolled congenital or acquired coagulation disorders.
8. Patients who have experienced cardiovascular/cerebrovascular disorders (including myocardial infarction, cerebral infarction, and transient ischemic attack) within 6 months before the date of informed consent.
9. Patients who have experienced deep vein thrombosis, pulmonary embolism and other serious thromboembolism (excluding intravenous catheter thrombosis or superficial intravenous thrombosis) within 6 months before the date of informed consent.
10. Patients with serious bleeding within 6 months before the date of informed consent.
11. Patients who experienced gastrointestinal perforation within 6 months before the date of informed consent, or patients who judged to be at risk of perforation (such as gastrointestinal infiltration, metastasis).
12. Patients with cirrhosis with Child-Pugh B or higher, or hepatic encephalopathy or hepatic ascites requiring intervention.
13. Patients with uncontrolled hypertension.
14. Patients with unhealed wounds or ulcerative lesions, or patients with a history of fracture within 28 days before the date of informed consent.
15. Patients who are pregnant, nursing or possibly pregnant.
16. Patients with uncontrolled metabolic diseases (such as diabetes mellitus).
17. Patients with active, uncontrolled infections.
18. Patients with regular administration of non-steroidal anti-inflammatory drugs and antiplatelet drugs.
19. Patients with medically high-risk or potentially life-threatening complications.
20. Any other patients who are regarded as unsuitable for this study by the investigators.

Related Information

• Primary Sponsor: Uchino Junji
• Source(s) of Monetary Support: Eli Lilly Japan K.K.