Carboplatin, Paclitaxel, and Ramucirumab for the Treatment of Stage IV or Recurrent Non-squamous Non-Small Cell Lung Cancer
- Histologic or cytologic diagnosis of non-squamous non-small cell lung cancer
- Stage IV non-small cell lung cancer or recurrent disease (stage IV or recurrent after initial curative intent therapy), which cannot be approached with curative intent
- Completion of minimum of 4 cycles of 1st-line carboplatin/pemetrexed/pembrolizumab
- Progression after at least 18 weeks of maintenance pemetrexed, pembrolizumab, or the combination of the two
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Age >= 18 years
- Measurable disease defined as at least one lesion that can be accurately measured in at least one dimension using 10 mm as the minimum longest diameter
- Patients must be capable of giving informed consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing
- Absolute neutrophil count (ANC) >= 1500/uL
- Hemoglobin >= 9 g/dL (5.58 mmol/L)
- Platelets >= 100,000/uL
- Total bilirubin =< 1.5 times the upper limit normal (ULN)
- Aspartate transaminase (AST) and alanine transaminase (ALT) =< 3.0 times the ULN or =< 5.0 times the ULN in the setting of liver metastases
- International normalized ratio (INR) =< 1.5, and a partial thromboplastin time (PTT) =< 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin must be switched to low molecular weight heparin or edoxaban or show stability on another Food and Drug Administration (FDA) approved oral anticoagulant with stable coagulation profile prior to first dose of protocol therapy. There may 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)
- Serum creatinine =< 1.5 times the ULN; or if serum creatinine is > 1.5 times the ULN, creatinine clearance (measured via 24-hour urine collection) must be >= 40 mL/minute
- Urinary protein is =< 1+ on dipstick or routine urinalysis (urine analysis [UA]: if urine dipstick or routine analysis is >= 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein)
- 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
- EGFR, EML4-ALK or ROS1 mutations susceptible for targeted therapy
- Other prior invasive malignancies requiring ongoing therapy (e.g. hormonal therapy for breast or prostate cancer)
- Peripheral neuropathy >= grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5)
- Grade 3-4 gastrointestinal (GI) bleeding within 3 months prior to first dose of protocol therapy
- Uncontrolled intercurrent illness including, but not limited to: uncontrolled ongoing infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Known human immunodeficiency virus (HIV) infection or untreated hepatitis C
- Untreated central nervous system metastases. Patients are eligible if they are clinically stable, on stable or tapering dose of steroids, after cranial irradiation (whole brain radiation therapy, focal radiation therapy, stereotactic radio surgery) ending at least 2 weeks prior to treatment start, or after surgical resection performed at least 2 weeks prior to treatment start
- Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, targeted therapy, or an investigational agent
- 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
- History of 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
- Uncontrolled or poorly-controlled hypertension (> 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical management
- History of hemoptysis (defined as bright red blood or >= 1/2 teaspoon) within 2 months prior to first dose of protocol therapy or radiographic evidence of intratumor cavitation or radiologically documented evidence of major blood vessel invasion or encasement by cancer
- Prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation
- Pregnant or breast-feeding
- Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy
- Major surgery within 28 days prior to first dose of protocol therapy; minor surgery/subcutaneous venous access device placement within 7 days prior to the first dose of protocol therapy; or elective or planned major surgery to be performed during the course of the clinical trial
- Chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted. Pro re nata (PRN) dosing of NSAIDs is permissible if the patient is not taking the medication on a standing basis
- A known history of anaphylaxis or severe hypersensitivity reaction to sb-paclitaxel, nab-paclitaxel or ramucirumab
- A known history of anaphylaxis or severe hypersensitivity reaction to carboplatin and failed desensitization to carboplatin
- Cirrhosis: * Level of Child-Pugh B (or worse) or * Any degree and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis defined as requiring diuretics or paracentesis
I. To estimate the overall response rate in patients treated with carboplatin/taxane/ramucirumab.
I. To estimate the progression-free survival (PFS).
II. To estimate the overall survival (OS).
III. To characterize the safety profile of combination re-induction and maintenance of carboplatin/taxane/ramucirumab after 1st-line platinum chemotherapy.
RE-INDUCTION: Patients receive ramucirumab intravenously (IV) over 60 minutes and carboplatin IV over 30 minutes on day 1. Patients also receive paclitaxel IV over 30 minutes on days 1 and 8. Treatments repeat every 21 days for 4-6 cycles per the discretion of the treating physician and in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive ramucirumab IV over 60 minutes on day 1. Patients also receive nab-paclitaxel IV over 30 minutes or Sb-paclitaxel IV over 60 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months.
Trial Phase Phase II
Trial Type Treatment
University of Pennsylvania / Abramson Cancer Center
Melina Elpi Marmarelis
- Primary ID 05519
- Secondary IDs NCI-2020-13703
- Clinicaltrials.gov ID NCT04332367