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Ziv-Aflibercept for Advanced Progressive Carcinoid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Matthew H. Kulke, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01782443
First received: January 31, 2013
Last updated: May 2, 2014
Last verified: May 2014
  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.


Condition Intervention Phase
Carcinoid Tumor
Drug: Ziv-aflibercept
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Ziv-aflibercept in Patients With Advanced, Progressive Carcinoid Tumors

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the progression-free survival (PFS) duration of patients with metastatic, unresectable, progressive carcinoid tumors treated with Ziv-aflibercept


Secondary Outcome Measures:
  • Safety and Tolerability of Ziv-aflibercept [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To determine the safety and tolerability of Ziv-aflibercept in patients with advanced carcinoid tumors

  • Evaluation of Disease Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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

  • Evaluation of Biochemical Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate biochemical response, using levels of chromogranin-A and urinary 5-HIAA measured at baseline and following treatment with Ziv-aflibercept.


Estimated Enrollment: 43
Study Start Date: February 2013
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental Treatment Arm
Ziv-aflibercept IV every 2 weeks, 4 mg/kg
Drug: Ziv-aflibercept

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01782443

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Matthew H. Kulke, MD, Prinicipal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01782443     History of Changes
Other Study ID Numbers: 12-456
Study First Received: January 31, 2013
Last Updated: May 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Progressive
Metastatic

Additional relevant MeSH terms:
Carcinoid Tumor
Adenocarcinoma
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors

ClinicalTrials.gov processed this record on November 25, 2014