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

Study Overview
=================
Brief Summary
-----------------
This research study is evaluating the drug Ramucirumab as a possible treatment for Advanced, Progressive Carcinoid Tumors.

Detailed Description
-----------------
This research study is a Phase II clinical trial. The purpose of this study is to test the safety and effectiveness of ramucirumab in advanced, progressive carcinoid tumors. Cancer cells can make growth factors that cause the abnormal growth of new blood vessels. Ramucirumab is an investigational drug which works by blocking a receptor for a vascular growth factor, thereby preventing new blood vessels from forming. This may stop the cancer from growing or spreading and the tumor cells may die. The FDA (the U.S. Food and Drug Administration) has not approved Ramucirumab for treatment of Carcinoid Tumors.

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

Conditions
-----------------
Carcinoid Tumors

Intervention / Treatment
-----------------
* Drug: Ramucirumab
* Drug: Somatostatin Analog


Participation Criteria
=================
Eligibility Criteria
-----------------
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 <1000 mg of protein in 24 hours) coagulation function Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) < 1.5 x institutional upper limit of normal. Patients on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin. The effects of ramucirumab on the developing human fetus are unknown. For this reason and because anti-antiangiogenic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of Ramucirumab administration. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients who have undergone major surgery within 28 days or subcutaneous venous access device placement within 7 days prior to study enrollment. Patients with elective or planned major surgery to be performed during the course of the clinical trial. Patients who are receiving any other investigational agents. Patients with any Grade 3-4 gastrointestinal bleeding within 3 months prior to enrollment. Patients with a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered significant) during the 3 months prior to registration. Patients who have 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 enrollment. Patients with uncontrolled or poorly-controlled hypertension (>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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ramucirumab In Combination With Somatostatin Analog<br>Patients will receive treatment with Ramucirumab at a pre-determined dose intravenously every 14 days of a 28-day treatment cycle. Patients will receive treatment with a Somatostatin Analog at a pre-determined dose. Toxicity and adverse events will be examined in the first 10 patients who complete one cycle of therapy before expanding enrollment. | Drug: Ramucirumab<br> <br> * Other names: Cyramza;Drug: Somatostatin Analog<br> <br> * Other names: lanreotide;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival Duration |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Event |  | 2 years | 
| Overall Survival Rate |  | 2 years | 
| Overall Radiographic And Biochemical Response Rate |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Carcinoid Tumors