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

Carcinoid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02795858
• Other study ID #: 16-072
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 14, 2016
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2024
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research study is evaluating the drug Ramucirumab as a possible treatment for Advanced, Progressive Carcinoid Tumors.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 43
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoid Tumor
• Carcinoid Tumors

Intervention

Drug:
• Ramucirumab

• Somatostatin Analog

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	To assess the progression-free survival duration of patients with advanced, progressive carcinoid tumors treated with ramucirumab in combination with somatostatin analog therapy. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) was used. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions. The appearance of one or more new lesions denotes disease progression. Partial Response (PR) is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	Survival collected every 12 weeks in long-term follow-up. The median survival follow-up time was 23.5 months (range 1.7 - 76.6 months)
Secondary	Overall Survival	To assess the overall survival duration of patients with advanced carcinoid tumors treated with ramucirumab. We will use the Kaplan-Meier method to estimate the distribution of overall survival.	The median survival follow-up time was 23.5 months (range 1.7 - 76.6 months)
Secondary	Overall Radiographic Response	To evaluate disease response using RECIST criteria, version 1.1, of patients with advanced carcinoid tumors treated with Ramucirumab.; Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT include the following categories of disease response: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable disease (SD), less than 30% decrease but no more than 20% increase in sum of the longest diameter of target lesions.; We will estimate the response rate and provide the associated 95% confidence interval.	2 years
Secondary	Biochemical Response (Chromogranin A)	To evaluate biochemical response in patients with elevated chromogranin A at baseline, using levels of chromogranin-A measured at baseline and following treatment with Ramucirumab. Biochemical response was defined as greater than 50% drop in chromogranin A from baseline.; During the screening period, all patients were evaluated for serum chromogranin A. Per protocol, if results of these are normal at baseline, they were not repeated while on study. If above institutional ULN at baseline, they were evaluated at time of tumor restaging.	2 years