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

NCT02795858 | Completed Phase 2 Results DMC

• 1 other identifier: 16-072
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Carcinoid Tumors

Keywords

Carcinoid Tumors

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall Survival

  The median survival follow-up time was 23.5 months (range 1.7 - 76.6 months)

• Overall Radiographic Response

  2 years

• Biochemical Response (Chromogranin A)

  2 years

Study Arms (1)

Ramucirumab In Combination With Somatostatin Analog

EXPERIMENTAL

Patients will receive treatment with ramucirumab starting at a dose of 8 mg/kg intravenously every 14 days of a 28-day treatment cycle. Patients already receiving a somatostatin analog continued somatostatin analog therapy at their current dose. Patients not already receiving a somatostatin analog initiated treatment at an approved dose, according to institutional guidelines. Toxicity and adverse events will be examined in the first 10 patients who complete one cycle of therapy before expanding enrollment.

Drug: Ramucirumab; Drug: Somatostatin Analog

Interventions

Ramucirumab DRUG

Also known as: Cyramza

Ramucirumab In Combination With Somatostatin Analog

Somatostatin Analog DRUG

Also known as: octreotide, lanreotide

Ramucirumab In Combination With Somatostatin Analog

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Eli Lilly and Company: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Perez K, Kulke MH, Zheng H, Allen J, Clark J, Enzinger AC, Enzinger PC, Johnson BE, McCleary NJ, Parikh A, Patel A, Rubinson D, Yurgelun MB, Ramsey K, Johnson E, Graham C, Chan JA. A phase II study of ramucirumab and somatostatin analog therapy in patients with advanced neuroendocrine tumors. Oncologist. 2025 Jan 17;30(1):oyae364. doi: 10.1093/oncolo/oyae364.

  PMID: 39834129 DERIVED

MeSH Terms

Conditions

Carcinoid Tumor

Interventions

Ramucirumab; Somatostatin; Octreotide; lanreotide

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pituitary Hormone Release Inhibiting Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pancreatic Hormones; Neuropeptides; Peptides; Nerve Tissue Proteins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Jennifer Chan, MD
• Organization: Dana-Farber Cancer Institute

jennifer_chan@dfci.harvard.edu

617-632-6315

Study Officials

• Jennifer A Chan, MD MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jennifer Ang Chan, MD

Study Record Dates

• First Submitted: June 7, 2016
• First Posted: June 10, 2016
• Study Start: June 14, 2016
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: February 19, 2025
• Results First Posted: March 5, 2024

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)