Phase II trial of ramucirumab and docetaxel for previously treated NSCLC patients with malignant pleural effusion

JRCT ID: jRCTs071190013

Registered date:02/07/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Advanced / recurrent non-small cell lung cancer (NSCLC)
• Date of first enrollment: 23/10/2019
• Target sample size: 15
• Study type: Interventional
• Intervention(s): Ramucirumab plus docetaxel combination chemotherapy are continued until break the cancellation criteria

Outcome(s)

• Primary Outcome: Pleural effusion control rate 8 weeks after the start of treatment
• Secondary Outcome: Objective response rate, Progression-free survival, One-year survival rate, Overall survival, Toxicity profile

Key inclusion & exclusion criteria

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

Include criteria

1) The patient has provided written consent after receiving sufficient explanation about the study prior to enrollment.
2) The patient is 20 years old or older on the day of enrollment.
3) The patient has histologically or cytologically confirmed NSCLC.
4) The patient's disease has a clinical staging of Stage IV.
4a) The patient with recurrent disease after adjuvant or neoadjuvant therapy or patients who have received combined chemotherapy and radiation for locally advanced disease are eligible, if:
- patient had progression disease within 6 months after completion of adjuvant or neoadjuvant platinum-based therapy (adjuvant therapy will be considered the patient's one and only prior firstline, platinum-based chemotherapy); or
- patient had progressive disease more than 6 months after completion of therapy AND has developed progressive disease on or after one subsequent chemotherapy regimen for advanced/metastatic disease.
5) The patient who have had disease progression during or after one and only one prior platinum-based chemotherapy regimen with or without maintenance therapy for advanced/metastatic disease or in combination with Immune check point inhibitor.
6) Maintenance chemotherapy is defined as therapy given within 42 days after the last dose of platinum-based chemotherapy in patients with ongoing clinical benefit (complete response, partial response, or stable disease) after platinum-based first-line induction chemotherapy.
7) The patient has clinically malignant pleural effusion and has not undergone pleurodesis after discontinuation of prior treatment.
8) The patient has asymptomatic brain metastasis or spinal metastasis that requires radiological or surgical intervention.
9) The patient does not have symptomatic superior vena cava syndrome.
10) The patient has no invasion or narrowing of major blood vessels due to cancer by radiologically documented evidence.
11) The patient has no cavity in tumor by radiologically documented evidence.
12) At least seven days have passed since the completion of radiation therapy for metastatic lesions to relieve symptoms. At least 28 days must have passed if the field of radiation therapy for symptom relief extended to the chest.
13) The patient has an ECOG PS of 0 or 1 at the time of enrollment.
14) The patient does not have
- 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.
15) The patient has adequate organ function, defined as:
White blood cells: >=3000/uL
Neutrophils: >=1500/uL
Hemoglobin: >=9.0g/dL
Platelets: >=10.0x104/uL
Total bilirubin: =<1.5 times the upper limit normal (ULN)
Aspartate aminotransferase (AST): =<3.0 times the ULN or 5.0 times the ULN in the setting of liver metastasis
Alanine aminotransferase (ALT): =<3.0 times the ULN or 5.0 times the ULN in the setting of liver metastasis
Creatinine: =<1.5 times the ULN, or creatinine clearance of 40 mL/min or more
International normalized ratio (INR): =<1.5 (=< 3.0 if patient is taking warfarin)
Prothrombin time and partial thromboplastin time: 1.5 x upper limit of normal (ULN)
Proteinuria: Less than 1+
16) The patient has agreed to practice medically approved methods of contraception (condom, pessary, etc.) if he/she has reproductive capacity.

Exclude criteria

1) The patient requires treatments for pleural effusion such as urgent (within 24 hours) and continuous pleuraleffusion drainage for displacement of the mediastinum due to accumulation of pleural effusion.
2) The patient has undergone major surgery within 28 days prior to enrollment, or subcutaneous venous access device placement within 7 days prior to enrollment. Furthermore, any patient with postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months will be excluded.
3) The patient has a planned major surgery during the course of the trial.
4) The patient is receiving concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, chemoembolization, or targeted therapy.
*The last dose of any chemotherapies including bevacizumab must be at least 28 days from the time of enrollment.
5) The patient has untreated CNS metastases. Patients with treated brain metastases are eligible if they are clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least 14 days prior to enrollment, or after surgical resection performed at least 28 days prior to enrollment. The patient may have no evidence of Grade >=1 CNS hemorrhage based on pretreatment MRI or IV contrast CT scan (performed within 21 days before enrollment).
6) The patient has radiologically documented evidence of major blood vessel invation or encasement by cancer
7) The patient has radiologic evidence of intratumor cavitation, regardless of tumor histology
8) The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy.
9) The patient is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents. Patients receiving prophylactic, low-dose anticoagulation therapy are eligible provided that the coagulation parameters defined in the inclusion criteria (INR=<1.5 or PT=<1.5 x ULN) are met.
10) The patient is receiving chronic therapy with nonsteroidal anti-inflammatory drugs (NSAIDs; for example, indomethacin, ibuprofen, naproxen, or similar agents) or receiving other antiplatelet agents (for example, clopidogrel, ticlopidine and dipyridamole). Aspirin use at doses up to 325 mg/day is permitted.
11) Patients with a history of hemoptysis within 2 months prior to enrollment.
12) The patient has clinically relevant congestive heart failure (NYHA II-IV) or cardiac arrhythmia poorly controlled by medications.
13) The patient has uncontrolled arterial hypertension >=150 / >=90 mm Hg despite standard medical management.
14) The patient has had a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to enrollment.
15) The patient has significant bleeding disorders, vasculitis, or experienced Grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to enrollment.
16) History of GI perforation and / or fistulae within 6 months prior to enrollment.
17) The patient has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
18) The patient has peripheral neuropathy >=Grade 2 (NCI-CTCAE v 4.0).
19) The patient has a serious illness or medical condition(s) including:
Known positive test results for human immunodeficiency virus (HIV), hepatitis B*, or hepatitis C antibodies (HCVb)
*Have evidence of or test positive for hepatitis B. A positive test for hepatitis B is defined as
- positive for hepatitis B surface antigen (HBsAg+)
OR
- positive for anti-hepatitis B core antibody (HBcAb+) and positive for hepatitis B deoxyribonucleic acid (HBV DNA)
OR
- positive for anti-hepatitis B surface antibody (HBsAb+) and positive for hepatitis B deoxyribonucleic acid (HBV DNA)
Acqired immunodeficiency syndrome (AIDS)-related illness.
Active or uncontrolled clinically serious infection.
Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to randomization.
Preexisting interstitial lung disease (ILD) as evidenced by Chest CT scan and/or X-ray at baseline
Have serious preexisting medical conditions or serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris or uncontrolled diabetes mellitus).
Known allergy or hypersensitivity reaction to any of the treatment components.
The patient has a known history of active drug abuse.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient ineligible for entry into this study.
20) The patient is pregnant (confirmed within 7 days prior to enrollment), or breastfeeding.
21) Patient is currently enrolled in or discontinued study drug (within 28 days prior to enrollment) from a clinical trial involving an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Patients participating in surveys or observational studies are eligible to participate in this study.
22) Prior therapy with ramucirumab and/or docetaxel.

Related Information

• Primary Sponsor: Shinnosuke Takeomto
• Secondary Sponsor: Fukuda Minoru,Eli Lilly and Campany