Ziv-Aflibercept for Advanced Progressive Carcinoid Tumors

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Brief Title

Ziv-Aflibercept for Advanced Progressive Carcinoid Tumors

Official Title

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

Brief 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. 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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Progression Free Survival

Secondary Outcome

 Safety and Tolerability of Ziv-aflibercept

Condition

Carcinoid Tumor

Intervention

Ziv-aflibercept

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

43

Start Date

February 13, 2013

Completion Date

December 2021

Primary Completion Date

June 2020

Eligibility 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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01782443

Organization ID

12-456


Responsible Party

Principal Investigator

Study Sponsor

Dana-Farber Cancer Institute


Study Sponsor

, , 


Verification Date

April 2020