A Phase II Study of Ramucirumab With Somatostatin Analog Therapy in Patients With Advanced, Progressive Carcinoid Tumors

Inclusion Criteria

• Participants must have histologically or cytologically confirmed low- to intermediate-grade neuroendocrine tumor (carcinoid tumor).
• Carcinoid tumors of any site are eligible. Patients with pancreatic neuroendocrine tumors are excluded.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 10 for the evaluation of measurable disease.
• Locally advanced, unresectable or metastatic disease.
• Patients must have evidence of radiographic disease progression within the past 12 months. Progressive disease by RECIST criteria is not required.
• Age ≥ 18 years.
• ECOG performance status 0-1 (see Appendix A).
• Participants must have normal organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/ mm3
• platelets ≥100,000/ mm3
• hemoglobin ≥ 9 g/dL
• total bilirubin ≤ 1.5 × institutional upper limit of normal
• AST(SGOT)/ALT(SGPT) ≤ 3 × institutional upper limit of normal, or ≤ 5× institutional upper limit of normal in the setting of liver metastases
• creatinine ≤ 1.5 × upper limit of normal
• urinary protein ≤ 1+ on dipstick or routine urinalysis (if urine dipstick or routine urinalysis is 2+, a 24-hour urine collection for protein must demonstrate 160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management.
• Patients who have congestive heart failure (NYHA Class III or IV), sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block within the six months preceding enrollment.
• Patients who 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.
• Patients with a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to enrollment.
• Patients receiving 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.
• Patients with uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
• Patients with prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years.
• Patients with symptomatic cholelithiasis.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Severely impaired lung function
• Any active (acute or chronic) or uncontrolled infection/ disorders.
• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
• Psychiatric illness/social situations that would limit compliance with study requirement
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ramucirumab .
• Pregnant and breastfeeding women are excluded from this study because ramucirumab is associated with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ramucirumab, breastfeeding should be discontinued if the mother is treated with ramucirumab. These potential risks may also apply to other agents used in this study.