Phase II study of ramucirumab in combination with erlotinib for untreated EGFR mutation-positive non-squamous non-small cell lung cancer patients with pleural effusion: RELAY-Effusio
- Conditions
- EGFR mutation positive advanced non-small cell lung cancer
- Registration Number
- JPRN-jRCTs051210138
- Lead Sponsor
- Kaneda Hiroyasu
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
1) Written informed consent.
2) Patients aged 20 years or older at the time of consent.
3) A diagnosis of non-squamous NSCLC has been confirmed cytologically or histologically.
4) Clinical Stage IV or postoperative recurrence.
5) EGFR exon 19 deletion or exon 21 (L858R) point mutation.
(1) Any testing is acceptable.
(2) Uncommon mutations are excluded.
6) Chemotherapy naive.
Participation in the study is permitted if adjuvant or neoadjuvant therapy (excluding EGFR-TKI) has been completed at least 6 months ago. However, a prior history of these treatments is not mandatory.
7) The presence of pleural effusion at the time of diagnosis.
(a) Diagnosis of carcinomatous pleurisy by pleural fluid cytology is desirable but not mandatory. (M1a may be diagnosed clinically if the effusion is on the affected side.)
(b) If the patient's general condition (e.g., mild heart failure) is assessed and the clinical diagnosis of malignant pleural effusion can be made, the patient can be enrolled, even if the patient has bilateral pleural effusion.
(c) Although patients with pleural effusion requiring drainage may be enrolled, pleural effusion should be drained as much as possible by the insertion of a chest drain or via thoracentesis by the date of enrollment. However, duration from the drain tube removement to enrollment must be at least 7days.
(d) Cases in which pleurodesis was performed are not allowed to be registered.
8) Evaluable lesions (with or without RECIST measurable lesions).
9) ECOG performance status 0 to 2.
10) The patient has adequate hematologic and organ function, defined as:
(1) Absolute neutrophil count (ANC) >=1,500/L
(2) Hemoglobin >=9.0 g/dL
(3) Platelets >=100,000/L
(4) Total bilirubin =<1.5
(5) Aspartate transaminase (AST) =< 100
(6) Alanine transaminase (ALT) =< 100
(7) Serum creatinine =<1.5, or creatinine clearance >=40 mL/minute (that is, if serum creatinine is >1.5, a 24-hour urine collection or Cockcroft-Gault method to calculate creatinine clearance must be performed).
(8) The patient's urinary protein is =<1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is >=2+, a 24-hour urine collection for protein must demonstrate <1,000 mg of protein in 24 hours to allow participation in this protocol).
(9) The patient has adequate coagulation function as defined by International Normalized Ratio (INR) =<1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) < 1.5 x upper limits of normal [ULN].). Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). If receiving warfarin, the patient must have an INR =<3.0. For heparin and LMWH there should be no active bleeding (that is, no bleeding within 14 days prior to first dose of protocol therapy) or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices).
(10) SpO2 of >=92% (indoor air).
11) The patient, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods). Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of protocol therapy.
12) Expected survival of 3 months or more.
1) The T790M EGFR mutation has been identified.
2) Known meningeal metastases, uncontrolled/unstable spinal cord compression, and symptomatic brain metastases. Brain metastases may be registered if (1) they are asymptomatic with treatment and (2) if steroids are used, the dose should be reduced to less than the equivalent of 10 mg of prednisolone.
3) The patient has undergone major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior to the first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial.
4) Pericardial effusion or ascites requiring drainage. However, asymptomatic pericardial effusion not requiring pericardiocentesis and with echocardiographic evidence of normal cardiac function may be registered.
5) The following numbers of days have not passed since radiation therapy, 7 or more days since the completion of irradiation for local relief or prophylaxis of symptoms (e.g., pain, bleeding, and obstruction) or 28 or more days since the completion of palliative radiation therapy to the chest (lung field and mediastinum).
6) Clinically relevant congestive heart failure (New York Heart Association, NYHA II-IV) or symptomatic or uncontrolled arrhythmias.
7) If the patient has the following serious illnesses or medical conditions,
(1) Severely immunocompromised patients (excluding those associated with steroid use) confirmed to be HIV-positive. (Measurement of HIV is not mandatory.)
(2) The patient has: cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
(3) History or concomitant malignancy diagnosed or treated at least 3 years prior to enrollment. (Lesions corresponding to carcinoma in situ or intramucosal carcinoma judged to be curative by local treatment are not included in active double cancers)
(4) Known allergic or hypersensitivity reactions to therapeutic components.
(5) The patient has a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered significant) during the 3 months prior to first dose of protocol therapy.
(6) The patient has a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy.
(7) Patients with other serious acute or chronic medical or psychiatric illnesses or laboratory abnormalities that may increase the risk of participating in the study or taking the study medication or may interfere with the interpretation of the study results and are deemed ineligible by the investigator.
8) Uncontrolled or poorly controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management.
9) The patient is receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
10) Patients that have received anticoagulants (excluding low-dose aspirin-containing antiplatelet agents) within 14 days or will require their administration during the study period. However, these patients may be enrolled if low-dose aspirin-co
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival
- Secondary Outcome Measures
Name Time Method Control rate of pleural effusion<br>Overall survival (OS)<br>Objective response rate (ORR) (complete response [CR] + partial response [PR]).<br>Disease control rate (DCR) (CR + PR + stable disease [SD]).<br>TTF (time to treatment failure)<br>Safety