Ramucirumab and Erlotinib in EGFR Exon 19 Deletion or L858R mutation Positive Treatment-naive Non-Small Cell Lung Cancer with High PD-L1 Expression

JRCT ID: jRCTs051220149

Registered date:12/01/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: non-small Cell Lung Cancer
• Date of first enrollment: 01/03/2023
• Target sample size: 25
• Study type: Interventional

Intervention(s)

Ramucirumab : i.v. once in 2 weeks
Erlotinib : oral, once daily for consecutive days
Treatment with regimen is continued until the rating of PD (progressive disease) or satisfaction of the protocol treatment discontinuation criteria.

Outcome(s)

• Primary Outcome: Progression-free survival (PFS)

Secondary Outcome

Overall response rate (ORR)
Disease control rate (DCR)
Overall survival (OS)
Safty
ORR, PFS, Time to treatment failure (TTF) for subsequent treatment

Key inclusion & exclusion criteria

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

Include criteria

1) Patients with histologically or cytologically confirmed non-small cell lung carcinoma.
2) Carcinoma at stage IV or postoperative recurrence not amenable to radical treatment.
3) Patients who have not received chemotherapy for the cancer covered by this study. Patients who have received preoperative or postoperative chemotherapy are eligible if the final chemotherapy dose was given at least 6 months prior to the date of registration in this study. Patients receiving EGFR-TKIs during preoperative or postoperative chemotherapy are not eligible.
4) EGFR exon 19 deletion or L858R mutation positive in tumor specimens (excluded if they have the T790M mutation).
5) High PD-L1 expression in tumors (Tumor PD-L1 >= 50% determined by PD-L1 IHC 22C3 pharmDx testing at each individual laboratory).
6) Patients able to take oral drugs.
7) Age 20 years old or older at the time of obtaining informed consent.
8) ECOG performance status(PS) of 0-2.
9) Patients free of severe disorders of major organs (bone marrow, heart, lungs, and liver) and satisfying the criteria given below (based on data collected within 14 days of registration, where the 14-day period is counted from the date of registration and includes the same day of the preceding week).
Neutrophils >=1,500 /mm3
Hemoglobin >=9.0 g/dL
Platelets >=100,000 /mm3
AST,ALT <=3.0xULN (upper limit of normal range)
(Patients with liver metastasis: <=5.0xULN)
Total bilirubin <=1.5xULN
Serum creatinine <=1.5xULN
or creatinine clearance >=40 mL/min
SpO2 (Room air) 90% or more
PT-INR<=1.5, and APTT longer by 5 seconds or less than the upper limit of normal range (unless receiving anticoagulant therapy)
*In patients receiving anticoagulant therapy, such as warfarin, the anticoagulant therapy should be replaced with low-molecular-weight heparin before
starting the protocol treatment and then PT-INR<=3.0 should be confirmed.
Urinary protein<=1+(test paper method, or less than 1,000 mg/day in 24-hour pooled urine
10)No restriction regarding the presence/absence of measurable lesions according to RECIST1.1.
11)Patients expected to survive for at least 3 months.
12)The absence of any prior treatments or procedures described below or in the case of prior treatments or procedures, the specified period of time has elapsed since the completion of prior treatments or procedures before registration in the study:
1.Higher invasive surgery (open abdominal/thoracic surgery)_Four weeks or longer has elapsed.
2.Thoracic drainage: One week or longer has elapsed since the postoperative removal of sutures.
3.Stereotactic radiation / gammaknife therapy for brain metastasis
Passage of 1 or more days from the final day of irradiation (final irradiation on the day of registration will not be accepted).
13)Obtainment of written consent from the patient himself/herself after sufficient explanation of the study content before registration in this study.

Exclude criteria

1) The patient has the T790M EGFR mutation in tumor specimens.
2) Spinal cord compression, symptomatic and unstable brain metastasis. Symptomatic brain metastases stable for at least 1 week with systemic steroids (prednisolone<=40mg/day equivalent) are allowed.
3) Developed grade 3 or higher gastrointestinal bleeding within 3 months before registration or hemoptysis (defined as bright red blood or >= 1/2 teaspoon, regardless of grade) within 2 months of registration.
4) Patients with imaging findings suggestive of macrovascular tumor invasion, tumor encasement, or hollowing within the tumor.
5) Patients with tumor exposure in the central airway up to the segmental branch.
6) Patients who have developed severe uncontrollable coagulation disorder or severe hemorrhagic complication within 6 months of registration.
7) Patients who have developed deep vein thrombus or pulmonary embolism within 3 months of registration.
8) Patients who underwent surgery within 4 weeks of registration (surgery on the date corresponding to 4 weeks before registration is acceptable, provided, skin tumor resection and endoscopic surgery are acceptable if one week or more has elapsed after surgery).
9) Active double cancer. Synchronous double cancer and metachronous double cancer with disease-free survival of within 2 years requiring treatment will be regarded as double cancer (except for carcinoma in situ in cases of potentially curative therapy with no evidence of disease recurrence).
10) Patients confirmed by MRI or cerebrospinal fluid test with meningeal dissemination.
11) Patients with cerebrovascular or neurovascular disease (including myocardial infarction, cerebral infarction, and transient ischemic attack) or other arterial thromboembolic events within 6 months of registration.
12) Patients with gastrointestinal perforation within 6 months of registration or with a risk for perforation (gastrointestinal invasion or metastasis).
13) Patients with poorly controlled hypertension (systolic blood pressure remaining 160 mmHg or higher and diastolic blood pressure remaining 100 mmHg or higher for 4 weeks or more) despite of appropriate management.
14) Patients with an unhealed wound or peptic ulcer.
15) Patients who developed fracture within 1 month of registration.
16) Patients with poorly controlled metabolic disease (diabetes mellitus) or other nonmalignant organ or systemic diseases or secondary effects of cancer associated with a high medical risk and / or uncertain survival prediction. Patients on continued insulin use are eligible if the condition is well-controlled.
17) Local infection or systemic active infection requiring surgical treatment, such as drainage.
18) Periodical users of non-steroidal anti-inflammatory drugs (NSAIDs : indomethacin, ibuprofen, naproxen, or analogous drugs) or anti-platelet drugs (aspirin, dipyridamole, ticlopidine, clopidogrel, or analogous drugs). Low-dose aspirin (325 mg/day or less) is acceptable. NSAIDs are acceptable if 7 days or more have elapsed after switching to acetaminophen.
19) Patients with liver cirrhosis rated Child-Pugh B or more severe or with hepatic encephalopathy or symptomatic hepatic ascites.
20) Active hepatitis B or hepatitis C (positive for HBs antibody, HBc antibody or HBs antigen are eligible if the virus level is lower than the detection limit and hepatitis is inactive, patients testing positive for HCV antibody are eligible if hepatitis is inactive).
21) Interstitial pulmonary disease evident on CT scan at the time of registration (positive history or organization of radiation pneumonitis is acceptable).
22) Clinically significant psychiatric disease, making registration difficult.
23) Complication by clinically significant ophthalmic disease [example: severe dry eye
syndrome (including Sjoren syndrome), dry kerato conjunctivitis, keratitis].
24) Patients requiring oral treatment with CYP3A4-inducing drugs or inhibitors.
25) Hypersensitivity to any ingredient or additive in ramucirumab or erlotinib.
26) Patients expected to undergo elective or planned major surgery during the course of the clinical trial.
27) Pregnant women, lactating women, or women unwilling to take contraceptive measures.
28) Other patients judged by the clinical investigator to be inappropriate for the study.

Related Information

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