Carcinoid TumorPhase 2NCT01782443
Ziv-Aflibercept for Advanced Progressive Carcinoid Tumors
A Phase 2 study testing Ziv-aflibercept in people with Carcinoid Tumor, run by Dana-Farber Cancer Institute at 3 sites in United States.
Trial summary
This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug, Ziv-aflibercept, is being studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoid Tumor
- What is being tested?
- Ziv-aflibercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 3 sitesUnited States
- Study dates
- 13 Feb 2013to 26 Dec 2021
- 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
- Histologically confirmed well differentiated or moderately differentiated neuroendocrine tumor from either a primary or metastatic site
- Must have disease that is not amenable to curative resection
- Must have evidence of disease progression within 12 months prior to study entry
- Must have measurable disease (RECIST 1.1)
- Prior chemoembolization of local ablative therapies are allowed, provided there is measurable disease outside of the area treated, or documented evidence of progression at the site of prior treatment
- No limit to number of prior treatments. Prior bevacizumab allowed unless discontinued due to unacceptable toxicity. Prior TKI targeting VEGF receptors allowed
Show all 10Show fewer
- Treatment with a somatostatin analog required for all subjects
- Subjects with history of hypertension must be adequately controlled
- Therapeutic anticoagulation is allowed. Must be on a stable dose of anticoagulant medication
- Must agree to use adequate contraception prior to study entry, for the duration of study participation and for 3 months after last administration of study drug
Who cannot join
- Prior treatment including chemoembolization within 4 weeks of study entry
- Major surgery within 4 weeks of study entry or minor surgery within 2 weeks of study entry
- Pregnant or breastfeeding
- Poorly differentiated carcinoma, high grade neuroendocrine tumor or small cell carcinoma
- Prior treatment with Ziv-aflibercept
- Pancreatic neuroendocrine tumor (islet cell carcinoma)will be excluded from this study. All non functional and functional islet cell carcinomas such as insulinoma, glucagonoma, gastrinoma, VIPoma will be excluded.
Show all 19Show fewer
- Not adequately recovered from toxicity of previous therapy
- Known untreated brain or other central nervous system metastases
- Known allergy to any of the study agents or to compounds of similar chemical or biologic composition
- History of congestive heart failure
- Symptomatic peripheral arterial disease
- Unhealed wounds, ulcers or bone fractures
- HIV positive or active Hepatitis infection
- History of abdominal fistula, GI perforation, intra abdominal abscess, uncontrolled GI bleeding, diverticulitis within 6 months of study entry
- History of arterial thrombotic events such as myocardial infarction, unstable angina pectoris or any ischemic or hemorrhagic cerebrovascular accident within the past 6 months
- No history of pulmonary embolism, DVT or vascular access related thrombosis if not also receiving adequate anticoagulation at a stable dose.
- No history of prior or synchronous malignancy except if treated with curative intent at least 3 years prior to study entry, or adequately treated non-melanoma skin cancer, cervical carcinoma in situ, or prostate intraepithelial neoplasia without evidence of prostate cancer
- Uncontrolled non-malignant illness that may increase the risks associated with study participation or may interfere with the conduct of the study or interpretation of study results
- Uncontrolled psychiatric illness or social situations that would limit compliance with study requirements
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02115
Brigham and Women's Hospital
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Phase II Study of Ziv-aflibercept in Patients With Advanced, Progressive Carcinoid Tumors
This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug, Ziv-aflibercept, is being studied. It also means that the FDA has not yet approved Ziv-aflibercept for use in patients with your type of cancer.
Every person has molecules in their bloodstream called vascular endothelial growth factors (VEGFs). These molecules help grow and sustain new blood vessels needed by the human body. Cancer tumors hijack this mechanism because they need new blod vessels and oxygen to grow. Ziv-aflibercept is an antibody. Antibodies are proteins that are produced naturally in our bodies and help to recognize foreign substances in our body. Ziv-aflibercept is a "targeted therapy" called a "VEGF Trap", that "traps" (binds) these VEGFs and prevents the cancer from using them to grow.
Read more
Though Ziv-aflibercept has not yet been FDA approved for the treatment of carcinoid tumors, it has recently been approved for patients with treatment-resistant colorectal cancer.
In this research study, we will use Ziv-aflibercept in combination with standard octreotide therapy to see if it slows the growth or spread of your carcinoid tumor. Standard octreotide (sandostatin) therapy is currently approved for treating symptoms of carcinoid tumors, such as those caused by carcinoid syndrome. Carcinoid syndrome is caused by hormones and other substances released by carcinoid tumors into the bloodstream. One of these secreted substances is serotonin, one of the body's natural chemical messengers. When excess serotonin secreted by the carcinoid tumors reaches the body's tissues, it is thought to cause diarrhea and redness (flushing) of the face, chest or back. Excess serotonin may also cause changes in the structure of the heart valves, which can impair the heart's function. Octreotide works by binding to receptors found on carcinoid tumors and prevents the release of hormones from the tumor.
Read the detailed description
If you are willing to participate in this study you will be asked to undergo some screening tests and procedures to confirm that you are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures include: a medical history, physical examination, CT or MRI, blood tests, serum chromogranin A, urine tests, 24-hour urine collection, pregnancy test and an electrocardiogram. If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.
If you meet the requirements for this study and you agree to continue your participation, you will receive Ziv-aflibercept every two weeks. Each dose of Ziv-aflibercept consists of an approximately 60 minutes infusion (through a needle into a vein). You will also receive an injection of Octreotide LAR (long acting release) monthly as part of your treatment for carcinoid tumor. This injection will be given to you by a nurse in your buttock. You may already be on Octreotide LAR. In that case, you will continue taking it at the same dose and schedule.
You will need to come to the clinic every two weeks while participating in this study. Each cycle is 28 days.
The following tests and procedures will be performed on Days 1 and 15 of each cycle: questions about your health, physical exam (Day 1 of each cycle only), vital signs, blood tests, pregnancy test (Day 1 of each cycle only).
Urine tests will be performed every other cycle.
The following tests and procedures will be done at the end of every third cycle: CT scan or MRI, Serum Chromogranin A, 24-hour urine collection.
After the final dose of the study drug the following tests and procedures will be performed: questions about your general health, physical exam, vital signs, blood tests, pregnancy test, EKG, Serum Chromogranin A, 24-hour urine collection.
- Conditions
- Carcinoid Tumor
- Being tested
- Ziv-aflibercept
- Keywords
- Progressive, Metastatic
- Medical subject headings
- Carcinoid Tumor, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ziv-afliberceptDrug
| Study group | Role | What they receive |
|---|---|---|
| Experimental Treatment Arm | Experimental | Ziv-aflibercept IV every 2 weeks, 4 mg/kg Receives: Drug: Ziv-aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
To evaluate the progression-free survival (PFS) duration of patients with metastatic, unresectable, progressive carcinoid tumors treated with Ziv-aflibercept. 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: 2 years
Secondary outcomes (3)
Evaluation of Disease Response
To evaluate disease response using RECIST criteria, version 1.1, of patients with advanced carcinoid tumors treated with Ziv-aflibercept.
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.
Measured: 2 years
Evaluation of Biochemical Response - Number of Patients With Greater Than 50% Drop in Chromogranin A From Baseline
To evaluate biochemical response in patients with elevated chromogranin A at baseline, using levels of chromogranin-A measured at baseline and following treatment with Ziv-aflibercept. 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
Biochemical Response - Number of Patients With Greater Than 50% Drop in 24hr Urine 5-HIAA From Baseline
To evaluate biochemical response in patients with elevated 24hr urine 5-HIAA at baseline, using levels of 24hr urine 5-HIAA at baseline and following treatment with Ziv-aflibercept. Biochemical response was defined as greater than 50% drop in 24hr urine 5-HIAA from baseline.
During the screening period, all patients were evaluated for 24hr urine 5HIAA. Per protocol, if results of these were 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 posted1 Feb 2013 (estimated)
- Study start13 Feb 2013
- Primary completionMar 2021
- Study completion26 Dec 2021
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 TumorStudies 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
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Chan, MD, MPH, Dana-Farber Cancer Institute
- Investigators
- Jennifer Chan, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01782443
- Sponsor's protocol ID
- 12-456
- Status last verified
- Aug 2023
- First submitted
- 31 Jan 2013
- Last updated
- 14 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Perez K, Kulke MH, Horick NK, Regan E, Graham C, Scheutz S, Stonely D, Enzinger PC, Fuchs CS, Allen JN, Enzinger AC, Clark JW, Chan JA. A Phase II Study of Ziv-Aflibercept in Patients With Advanced Extrapancreatic Neuroendocrine Tumors. Pancreas. 2022 Aug 1;51(7):763-768. doi: 10.1097/MPA.0000000000002099.
PubMed 36395401
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Ziv-aflibercept in Patients With Advanced, Progressive Carcinoid Tumors
- ClinicalTrials.gov ID
- NCT01782443
- Acronym / sponsor ID
- 12-456
- Conditions
- Carcinoid Tumor
- Keywords
- Progressive, Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- 13 Feb 2013 (actual)
- Primary completion
- Mar 2021 (actual)
- Study completion
- 26 Dec 2021 (actual)
- First posted
- 1 Feb 2013 (estimated)
- Results
- Posted 9 Nov 2022
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 a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug, Ziv-aflibercept, is being studied. It also means that the FDA has not yet approved Ziv-aflibercept for use in patients with your type of cancer.
Every person has molecules in their bloodstream called vascular endothelial growth factors (VEGFs). These molecules help grow and sustain new blood vessels needed by the human body. Cancer tumors hijack this mechanism because they need new blod vessels and oxygen to grow. Ziv-aflibercept is an antibody. Antibodies are proteins that are produced naturally in our bodies and help to recognize foreign substances in our body. Ziv-aflibercept is a "targeted therapy" called a "VEGF Trap", that "traps" (binds) these VEGFs and prevents the cancer from using them to grow.
Though Ziv-aflibercept has not yet been FDA approved for the treatment of carcinoid tumors, it has recently been approved for patients with treatment-resistant colorectal cancer.
In this research study, we will use Ziv-aflibercept in combination with standard octreotide therapy to see if it slows the growth or spread of your carcinoid tumor. Standard octreotide (sandostatin) therapy is currently approved for treating symptoms of carcinoid tumors, such as those caused by carcinoid syndrome. Carcinoid syndrome is caused by hormones and other substances released by carcinoid tumors into the bloodstream. One of these secreted substances is serotonin, one of the body's natural chemical messengers. When excess serotonin secreted by the carcinoid tumors reaches the body's tissues, it is thought to cause diarrhea and redness (flushing) of the face, chest or back. Excess serotonin may also cause changes in the structure of the heart valves, which can impair the heart's function. Octreotide works by binding to receptors found on carcinoid tumors and prevents the release of hormones from the tumor.
Detailed description
If you are willing to participate in this study you will be asked to undergo some screening tests and procedures to confirm that you are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures include: a medical history, physical examination, CT or MRI, blood tests, serum chromogranin A, urine tests, 24-hour urine collection, pregnancy test and an electrocardiogram. If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study.
If you meet the requirements for this study and you agree to continue your participation, you will receive Ziv-aflibercept every two weeks. Each dose of Ziv-aflibercept consists of an approximately 60 minutes infusion (through a needle into a vein). You will also receive an injection of Octreotide LAR (long acting release) monthly as part of your treatment for carcinoid tumor. This injection will be given to you by a nurse in your buttock. You may already be on Octreotide LAR. In that case, you will continue taking it at the same dose and schedule.
You will need to come to the clinic every two weeks while participating in this study. Each cycle is 28 days.
The following tests and procedures will be performed on Days 1 and 15 of each cycle: questions about your health, physical exam (Day 1 of each cycle only), vital signs, blood tests, pregnancy test (Day 1 of each cycle only).
Urine tests will be performed every other cycle.
The following tests and procedures will be done at the end of every third cycle: CT scan or MRI, Serum Chromogranin A, 24-hour urine collection.
After the final dose of the study drug the following tests and procedures will be performed: questions about your general health, physical exam, vital signs, blood tests, pregnancy test, EKG, Serum Chromogranin A, 24-hour urine collection.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental Treatment Arm | Experimental | Drug: Ziv-afliberceptZiv-aflibercept IV every 2 weeks, 4 mg/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically confirmed well differentiated or moderately differentiated neuroendocrine tumor from either a primary or metastatic site
- Must have disease that is not amenable to curative resection
- Must have evidence of disease progression within 12 months prior to study entry
- Must have measurable disease (RECIST 1.1)
- Prior chemoembolization of local ablative therapies are allowed, provided there is measurable disease outside of the area treated, or documented evidence of progression at the site of prior treatment
Key exclusion criteria (19 listed)
- Prior treatment including chemoembolization within 4 weeks of study entry
- Major surgery within 4 weeks of study entry or minor surgery within 2 weeks of study entry
- Pregnant or breastfeeding
- Poorly differentiated carcinoma, high grade neuroendocrine tumor or small cell carcinoma
- Prior treatment with Ziv-aflibercept
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 |
|---|---|---|
| Ziv-aflibercept | Drug | Experimental Treatment Arm |
Primary outcome
Progression Free Survival
Time frame: 2 years
To evaluate the progression-free survival (PFS) duration of patients with metastatic, unresectable, progressive carcinoid tumors treated with Ziv-aflibercept. 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
Evaluation of Disease Response
Time frame: 2 years
Evaluation of Biochemical Response - Number of Patients With Greater Than 50% Drop in Chromogranin A From Baseline
Time frame: 2 years
Biochemical Response - Number of Patients With Greater Than 50% Drop in 24hr Urine 5-HIAA From Baseline
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 14 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36395401Perez K, Kulke MH, Horick NK, Regan E, Graham C, Scheutz S, Stonely D, Enzinger PC, Fuchs CS, Allen JN, Enzinger AC, Clark JW, Chan JA. A Phase II Study of Ziv-Aflibercept in Patients With Advanced Extrapancreatic Neuroendocrine Tumors. Pancreas. 2022 Aug 1;51(7):763-768. doi: 10.1097/MPA.0000000000002099.
Related trials for Carcinoid Tumor
RecruitingPhase 3
Somatostatin Analogues vs. Observation After Peptide Receptor Radionuclide Therapy (PRRT) in Nonfunctional Neuroendocrine Neoplasms
Neuroendocrine Neoplasm, Gastroenteropancreatic Neuroendocrine Neoplasm
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingObservational study
Natural History of Familial Carcinoid Tumor
Carcinoid
RecruitingObservational study
Biomarkers in Patients With Respiratory Tract Dysplasia or Lung Cancer, Head and Neck Cancer, or Aerodigestive Tract Cancer and in Normal Volunteers
Esophageal Cancer, Head and Neck Cancer
RecruitingPhase 1
Study of RYZ401 in Subjects With Solid Tumors Expressing SSTRs.
GEP-NET, Gastroenteropancreatic Neuroendocrine Tumor
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 Chan, MD principal investigator
Dana-Farber Cancer Institute
3 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 Ziv-aflibercept in people with Carcinoid Tumor, run by Dana-Farber Cancer Institute at 3 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 10 inclusion and 19 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 14 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 9 Nov 2022). 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 (time frame: 2 years). 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 NCT01782443, 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 14 Aug 2023.