Docetaxel plus Ramucirumab with pegylated granulocyte-colony stimulating factor support for elderly patients with advanced non-small cell lung cancer: A multicenter prospective single arm phase II study (WJOG9416L)

JRCT ID: jRCTs051180232

Registered date:30/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: non-small cell lung cancer
• Date of first enrollment: 28/03/2018
• Target sample size: 65
• Study type: Interventional
• Intervention(s): DOC (60 mg/m2, day 1) &PEG-G-CSF (3.6 mg, single-dose administration between day 2 and 4) + RAM (10 mg/kg, day 1) These drugs will be administered every 3 weeks. This therapy will be continued until both DOC and RAM are discontinued or protocol treatment is evaluated as ineffective.

Outcome(s)

• Primary Outcome: Response rate
• Secondary Outcome: Progression-free survival, overall survival, and safety

Key inclusion & exclusion criteria

• Age minimum: >= 75age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(Informed consent)
1. Aged older than 75
2. Written informed consent
(histology)
3. Histological or cytologically proven NSCLC
(Disease extension)
4. stage IIIB/IIIC without indication of curative radiation, stage IV or recurrence postoperation
5. With measurable disease (RECIST v1.1)
6. Without symptomatic brain metastases or spinal metastases with indication of radiation or surgery
7. Without symptomatic SVC syndrome
8. Without uncontrolled cardiac, pleural, abdominal effusion
9. Restriction of Radiological findings
I. Without tumor invasion to main bronchus and/or main vessels
II. Without cavitation regardless of histology
III. Without appearance of tumor in main bronchus
(General status and labo data)
10. ECOG PS 0 or 1
11. Labo data (within 14 days from registration day)
WBC more than 3,000/mm3
Neutrophil more than 1,500/mm3
Hb more than 9.0 g/dL
Platelet more than 10x104 / mm3
T-bil less than 1.5 mg/dL
AST and ALT less than 100 IU/L (in cases with liver metastases less than 200 IU/L)
CRE less than 1.5 mg/dL, or CCR more than 40 mL/min
PT (INR) less than 1.5
SpO2(room air) more than 92% , or PaO2 more than 60
Patients with a urinary protein level of less than 1+. In those with a level of more than 2+, 24-hour urine collection should be performed, and they are regarded as eligible if the 24-hour protein level is less than 1,000 mg.
12. HBs antigen-negative patients (HBs antibody- and/or HBc antibody-positive patients are regarded as eligible if they are negative for HBV-DNA).
(Pretreatment)
13. No history of cytotoxic chemotherapies and RAM. In patients with EGFR-mutations (Del-19/L858R) or ALK-fusions, treatment with EGFR/ALK-TKIs are completed as prior therapies (regardless of the reasons for completion). In patients receiving prior immune-checkpoint inhibitors, progressive disease are confirmed or they are terminated after intolerable adverse events.
14. One regimen of postoperative chemotherapy is acceptable. In this case; The interval from the final day of administration during postoperative chemotherapy is longer than 24 weeks. For regimens with platinum preparations, the change of platinum preparations should be regarded as 1 regimen. Concerning patients treated by postoperative chemotherapy with EGFR/ALK-TKIs in whom relapse is confirmed 31 days or more after the final day of administration, additional EGFR/ALK-TKI therapy is completed. With respect to relapse within 30 days in patients treated by postoperative chemotherapy with EGFR/ALK-TKIs, treatment with EGFR/ALK-TKIs is regarded as being completed.
15. Surgery under general anesthesia has not been performed within 28 days before registration.
No subcutaneous vein access instrument has been inserted within 7 days before registration.
In patients who underwent surgery during the past 2 months, postoperative hemorrhage, complications, and wound complications are absent.
16. The interval from the completion of radiotherapy for metastatic foci (including gamma-knife therapy for metastatic foci of the brain) is 1 week (Day 8 or later, regarding the day of completion as Day 1).
17. In patients receiving thoracic radiation therapy, measurable lesions exist in extra-radiation field after 24 weeks since completion of radiation.
18. There is no history of thoracic radiotherapy or chemotherapy for other types of cancer. However, surgery and hormonal therapy for other types of cancer are acceptable (oral anticancer drug therapy, as postoperative adjuvant chemotherapy for other types of cancer, is acceptable if the interval from the completion of oral administration is longer than 5 years).

Exclude criteria

(Double cancer)
1. Patients with active double cancer (synchronous double/multiple cancer and metachronal double/multiple caner with a disease-free period of shorter than 5 years). However, carcinoma in situ (intra-epithelial carcinoma) that may have been cured by topical treatment or intramucosal carcinoma lesions are not included in the category of active double/multiple cancer.
(Complications)
2. Those with infectious diseases requiring systemic treatment
3. Those with interstitial pneumonia or pulmonary fibrosis on thoracic CT
4. Those with diabetes mellitus in whom control is unfavorable
5. Those with arterial hypertension (systolic blood pressure: more than150 mmHg or diastolic blood pressure: more than 90 mmHg) that cannot be controlled despite standard medical management
6. Those with clinically significant congestive heart failure (NYHA II-IV) or arrhythmia that cannot be controlled with drugs
7. Those with a history/present illness of ileus, inflammatory bowel disease, extensive intestinal resection (hemicolectomy for chronic diarrhea or extensive small intestinal resection), Crohns disease, ulcerative colitis, or chronic diarrhea
8. Those with a history of thrombotic disorder that is impossible to control
9. Those with acquired immunodeficiency syndrome (AIDS)-associated diseases
10. Those with psychiatric disease or symptoms in whom study participation is considered difficult
11. Those with a history of Child-Pugh grade B (or severer) liver cirrhosis, hepatic encephalopathy, or liver cirrhosis with clinically important ascites (regardless of the severity)
:Clinically important ascites related to liver cirrhosis is defined as a condition requiring continuous treatment with diuretics or by puncture.
(Treatment for other diseases)
12. Those receiving the continuous systemic (oral or intravenous) administration of steroids or other immunosuppressive agents
13. Those receiving anticoagulant therapy with Warfarin, low-molecular-weight heparin, or analogues. : Patients receiving preventive low-dose anticoagulant therapy may be registered if they meet the coagulation parameters described in selection criteria (INR: less than 1.5).
14) Those receiving long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs; indomethacin, ibuprofen, naproxen, or analogues)
or those receiving other antiplatelet drugs (clopidogrel, ticlopidine, and dipyridamole): The use of low-dose aspirin (up to 325 mg/day) is acceptable: The administration of NSAIDs must be completed before 7 days prior to registration. During the study period, their use as a potion within 10 consecutive days is acceptable.
(General condition)
15. Those with fever (axillary temperature: more than 38C) at the time of registration
16. Those with a history of hemoptysis within 2 months before registration
17. Those with arterial thrombosis, such as myocardial infarction, unstable angina, cerebrovascular attacks, or transient cerebral ischemic attacks, within 6 months before registration
18. Those with serious or refractory wounds, ulcers, or fracture within 28 days before registration
19. Those with serious bleeding disorder, angitis, or grade 3 or higher gastrointestinal hemorrhage within 3 months before registration
20. Those with gastrointestinal perforation or fistulae within 6 months before registration
21. Those with a history of hypersensitivity to drugs, including polysorbate 80
22. Those for whom major surgery is scheduled during the trial period

Related Information

• Primary Sponsor: Hata Akito
• Secondary Sponsor: Nakagawa Kazuhiko
• Source(s) of Monetary Support: Eli Lilly Japan
• Secondary ID(s): UMIN000030598