DTX+RAM PII

JRCT ID: jRCTs041190077

Registered date:07/11/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Non-small cell lung cancer
• Date of first enrollment: 16/01/2020
• Target sample size: 32
• Study type: Interventional

Intervention(s)

RAM: 10 mg/kg, day 1 of every 3-week cycle
DTX: 60 mg/m2, day 1 of every 3-week cycle

Outcome(s)

• Primary Outcome: Objective Response Rate
• Secondary Outcome: Safety, PFS, OS

Key inclusion & exclusion criteria

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

Include criteria

1. Patients with histologically or cytologically confirmed NSCLC.
2. Patients with stage III NSCLC without indication for radical thoracic irradiation and stage IV/recurrent NSCLC.
3. Patients who have had disease progression during or after first-line platinum-based chemotherapy combined with ICI regimen with or without maintenance therapy for advanced/metastatic disease.
* Driver gene-targeted therapies are allowed in patients with driver gene abnormality, such as EGFR, ALK, ROS1, etc.
4. Patients aged 20 years or older.
5. Patients with an ECOG PS of 0 or 1.
6. Patients who have measurable disease at the time of registration documented by computed tomography (CT) scan or magnetic resonance imaging (MRI), as defined by the Response Evaluation Criteria in Solid Tumor (RECIST) Guidelines, version 1.1.
7. Patients who have resolution to Grade <=1 of all clinically significant toxic effects of prior anticancer therapy (locoregional therapy, surgery, or others) according to the Japanese Clinical Oncology Group Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0.
8. Patients without symptomatic brain metastasis or carcinomatous meningitis.
9. Patients without Grade 3 or more SVC syndrome, cardiac effusion, and pleural effusion (patients with stable disease (SD) of pleural effusion > 14 days after drainage are allowed).
10. Patients with adequate organ function, defined as follows:
* Patients with adequate hepatic function as defined by a total bilirubin <= 1.5 times the upper limit normal (ULN), and aspartate transaminase (AST) and alanine transaminase (ALT) <= 3.0 times the ULN or 5.0 times the ULN in the setting of liver metastases. 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 resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis.
* Serum creatinine <= 1.5 x ULN or calculated creatinine clearance >= 40 ml/min (per the Cockcroft-Gault formula or equivalent and/or 24-h urine collection).
* Absolute neutrophil count (ANC) >= 1.5 x 103/micro liter, hemoglobin >=10.0 g/dl, and platelets >= 100 x 103/micro liter.
* The patient must have adequate coagulation function, as defined by the international normalized ratio (INR) <= 1.5, and a partial thromboplastin time (PTT) <= 5 s above the ULN.
11. Patients who do not exhibit findings of interstitial lung disease in the chest CT evaluation.
12. Patients with urinary protein <= 1 + on dipstick or routine urinalysis (UA) (if urine dipstick or routine UA indicates proteinuria >= 2 +, then a 24-h urine must be collected and must demonstrate < 1000 mg of protein in 24 h to allow participation in the study).
13. Eligible patients of reproductive potential (both sexes) must agree to use medically approved contraceptive precautions during the study period and for 4 months following the last dose of study drug or until it is safe for the patient to become pregnant as indicated by the investigator.
14. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to registration.
15. The patient has a life expectancy of >= 3 months.
16. Prior radiation therapy is allowed if:
* In the case of chest radiotherapy, at least 90 days has elapsed from the completion of radiation treatment prior to registration.
* In the case of focal or palliative radiation treatment for bone metastasis, at least 14 days has elapsed from last the radiation treatment prior to registration (and provided that 25 percent or less of total bone marrow had been irradiated).
* In the case of CNS radiation, at least 14 days has elapsed from the completion of radiation treatment prior to registration.
17. Patients with written informed consent.

Exclude criteria

1. The patient's tumor wholly or partially contains small cell lung cancer.
2. The patient has undergone major surgery within 28 days prior to registration or subcutaneous venous access device placement within 7 days prior to registration. 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 scheduled 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 anticancer therapy must be at least 28 days prior to registration.
* The last dose of bevacizumab must be at least 28 days prior to registration.
5. The patient has radiologically documented evidence of major blood vessel invasion or encasement by cancer.
6. The patient has radiographic evidence of intratumor cavitation, regardless of tumor histology.
7. The patients have a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or other severe thromboembolic events (Venous port thrombosis, catheter thrombosis, or superficial vein thrombosis are excluded.) within 3 months prior to registration.
8. Patients with a history of hemoptysis within 2 months prior to registration.
9. Patients with a medication history of antiplatelet (aspirin 325 mg/day or more, clopidogrel, ticlopidine, dipyridamole) within 14 days, anti-vitamin K, or anticoagulation therapy.
10. The patient has clinically relevant congestive heart failure (CHF) (NYHA II-IV) or cardiac arrhythmia poorly controlled by medications.
11. The patient has experienced any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to registration.
12. The patient has uncontrolled arterial hypertension >= 150/ >=90 mm Hg despite standard medical management.
13. The patient has had a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to registration.
14. The patient has significant bleeding disorders or vasculitis or has experienced Grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to registration.
15. History of GI perforation and/or fistulae within 6 months prior to registration.
16. 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.
17. The patient has a CTCAE Grade 2 or more peripheral neuropathy.
18. 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 (HCVAb).
* Have evidence of or test positive for hepatitis B. A positive test for hepatitis B is defined as follows:
- 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 HBV DNA
* Acquired 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 registration.
* Preexisting interstitial lung disease 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 (e.g., unstable angina pectoris or uncontrolled diabetes mellitus).
* The patient has clinically significant third-space fluid retention (e.g., ascites or pleural effusion), which persists despite repeated drainage or requires repeated drainage.
* 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.
19. The patient is pregnant or breastfeeding.
20. Prior therapy with RAM and/or DTX.

Related Information

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