Boston, Massachusetts 02215

  • Carcinoid Tumor

Purpose:

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.


Study summary:

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.


Criteria:

Inclusion Criteria: - 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 - 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 Exclusion Criteria: - 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. - 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


Study is Available At:


Original ID:

12-456


NCT ID:

NCT01782443


Secondary ID:


Study Acronym:


Brief Title:

Ziv-Aflibercept for Advanced Progressive Carcinoid Tumors


Official Title:

Phase II Study of Ziv-aflibercept in Patients With Advanced, Progressive Carcinoid Tumors


Overall Status:

Active, not recruiting


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Dana-Farber Cancer Institute


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

43


Enrollment Type:

Anticipated


Study Dates

Start Date:February 13, 2013
Completion Date:December 2021
Completion Type:Anticipated
Primary Completion Date:March 2021
Primary Completion Type:Anticipated
Verification Date:January 2021
Last Changed Date:January 12, 2021
First Received Date:January 31, 2013

Study Outcomes

Outcome Type:Primary Outcome
Measure:Progression Free Survival
Time Frame:2 years
Safety Issues:False
Description:To evaluate the progression-free survival (PFS) duration of patients with metastatic, unresectable, progressive carcinoid tumors treated with Ziv-aflibercept
Outcome Type:Secondary Outcome
Measure:Evaluation of Biochemical Response
Time Frame:2 years
Safety Issues:False
Description:To evaluate biochemical response, using levels of chromogranin-A and urinary 5-HIAA measured at baseline and following treatment with Ziv-aflibercept.
Outcome Type:Secondary Outcome
Measure:Evaluation of Disease Response
Time Frame:2 years
Safety Issues:False
Description:To evaluate disease response (Partial Response [PR], Complete Response [CR], Stable disease [SD], using RECIST criteria, version 1.1 of patients with advanced carcinoid tumors treated with Ziv-aflibercept
Outcome Type:Secondary Outcome
Measure:Safety and Tolerability of Ziv-aflibercept
Time Frame:2 years
Safety Issues:False
Description:To determine the safety and tolerability of Ziv-aflibercept in patients with advanced carcinoid tumors

Study Interventions

Intervention Type:Drug
Name:Ziv-aflibercept
Arm Name:Experimental Treatment Arm

Study Arms

Study Arm Type:Experimental
Arm Name:Experimental Treatment Arm
Description:Ziv-aflibercept IV every 2 weeks, 4 mg/kg

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Dana-Farber Cancer Institute

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: September 23, 2021

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