Carcinoid TumorsPhase 2NCT02795858
A Phase II Study of Ramucirumab With Somatostatin Analog Therapy in Patients With Advanced, Progressive Carcinoid Tumors
A Phase 2 study testing Ramucirumab and Somatostatin Analog in people with Carcinoid Tumors, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
This research study is evaluating the drug Ramucirumab as a possible treatment for Advanced, Progressive Carcinoid Tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoid Tumors
- What is being tested?
- Ramucirumab and Somatostatin Analog
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 Jun 2016to 31 Dec 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
This research study is evaluating the drug Ramucirumab as a possible treatment for Advanced, Progressive Carcinoid Tumors.
Read the 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.
- Conditions
- Carcinoid Tumors
- Being tested
- Ramucirumab, Somatostatin Analog
- Keywords
- Carcinoid Tumors
- Medical subject headings
- Carcinoid Tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RamucirumabDrug
Also called Cyramza
Somatostatin AnalogDrug
Also called octreotide, lanreotide
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ramucirumab; Drug: Somatostatin Analog |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: The median survival follow-up time was 23.5 months (range 1.7 - 76.6 months)
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.
Measured: 2 years
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2016 (estimated)
- Study start14 Jun 2016
- Primary completion31 Dec 2022
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoid TumorsStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute
- Investigators
- Jennifer A Chan, MD MPH, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02795858
- Sponsor's protocol ID
- 16-072
- Status last verified
- Feb 2025
- First submitted
- 7 Jun 2016
- Last updated
- 19 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 39834129
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Ramucirumab With Somatostatin Analog Therapy in Patients With Advanced, Progressive Carcinoid Tumors
- ClinicalTrials.gov ID
- NCT02795858
- Acronym / sponsor ID
- 16-072
- Conditions
- Carcinoid Tumors
- Keywords
- Carcinoid Tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- 14 Jun 2016 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 10 Jun 2016 (estimated)
- Results
- Posted 5 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ramucirumab In Combination With Somatostatin Analog | Experimental | Drug: Ramucirumab, Drug: Somatostatin AnalogPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RamucirumabAlso: Cyramza | Drug | Ramucirumab In Combination With Somatostatin Analog |
| Somatostatin AnalogAlso: octreotide, lanreotide | Drug | Ramucirumab In Combination With Somatostatin Analog |
Primary outcome
Progression-Free Survival (PFS)
Time frame: 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)
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.
3 secondary outcomes
Overall Survival
Time frame: The median survival follow-up time was 23.5 months (range 1.7 - 76.6 months)
Overall Radiographic Response
Time frame: 2 years
Biochemical Response (Chromogranin A)
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39834129Perez 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer A Chan, MD MPH principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ramucirumab and Somatostatin Analog in people with Carcinoid Tumors, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02795858, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2025.