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Yttrium Microspheres With Cetuximab Plus Irinotecan for Patients With Advanced Colorectal Cancer Mets to Liver

Primary Purpose

Colon Cancer, Colorectal Cancer

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
SIR-spheres Agent Administration
Cetuximab
Irinotecan
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colon Cancer focused on measuring Colon, Liver, Colorectal cancer, Colorectal cancer metastases to the liver, Metastases to the liver, Colorectal cancer mets to liver, Colon cancer metastasized to liver, Yttrium microspheres, SIR-Spheres, Yttrium-90, Cetuximab, C225, Erbitux, IMC-C225, Irinotecan, CPT-11, Liver directed therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients must have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Histology from the hepatic metastasis is not mandatory if the morphological appearances on cross sectional imaging and tumor markers (CEA) are indicative of a colorectal primary.
  2. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in two dimensions (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT scan.
  3. Patients must have radiological evidence of disease progression of disease within 6 months of their most recent dose of chemotherapeutic regimens .
  4. Age greater than or equal to 18 years.
  5. ECOG performance status less than or equal to 2.
  6. Patients must have normal organ and marrow function as defined below within 30 days of receiving the investigational agent: - leukocytes greater than or equal to 3,000/mL - absolute neutrophil count greater than or equal to 1,500/mL - platelets greater than or equal to 100,000/mL - total bilirubin less than or equal to 1.5 times upper limits of normal institutional limits - AST(SGOT) less than or equal to 3 X ULN and ALT(SGPT) less than or equal to 3 X ULN - Creatinine less than or equal to 1.5 times upper limits of normal institutional limits
  7. Patients with a prior history of non-colorectal cancer who have no active disease may be eligible if they are disease free for greater than or equal to 12 months prior to treatment.
  8. The effects of SIR-Spheres, irinotecan or cetuximab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because radiation as well as other therapeutic agents used in this trial 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 in this study, she should inform her treating physician immediately.
  9. Ability to understand and the willingness to sign a written informed consent document.
  10. Patients without evidence of local disease recurrence from colorectal cancer are eligible
  11. Patients with extrahepatic disease confined to the lung is permitted if < 4 lesions are depicted on CTand all are < 3 cm in size
  12. Patients with brain mets are eligible for this trial if those patients who have had the area surgically resected or irradiated and have no evidence of active disease as demonstrated by MRI of the brain. Patients must have no evidence of residual neurological dysfunction as per baseline neurological exam. Patients with untreated brain metastases will be considered ineligible.

Exclusion Criteria:

  1. Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier will be excluded. Patients who have had hepatic external beam radiotherapy will be excluded.
  2. Patients may not be receiving any other investigational agents.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to SIR-Spheres, irinotecan or cetuximab or other agents used in the study.
  4. Evidence of ascites, biopsy proven cirrhosis or portal hypertension suggested by the presence of characteristic imaging features on cross sectional imaging or esophageal varicosities demonstrated on endoscopy or barium swallow. A diagnostic study to rule out the presence of portal hypertension will not be required unless the findings on cross sectional imaging are suggestive but not confirmatory.
  5. Hepatic arterial anatomy that would prevent catheterization and the administration of SIR-Spheres into the liver.
  6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring hospital admission or antibiotics,symptomatic congestive heart failure (class III and IV), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations would exclude patients from this study.
  7. Contraindications to angiography and selective visceral catheterization: History of severe allergy or intolerance to any contrast media, or atropine. Bleeding diathesis, not correctable by usual forms of therapy that would include medical coagulopathy but not limited to the administration of blood products.
  8. Utilization of capecitabine for the 6 weeks preceding SIR-Sphere therapy and indefinitely following SIR-Sphere therapy as per manufacturer's recommendations due to the increased risk of radiation hepatitis.
  9. Patients exhibiting the mutant variety for kras will be excluded for participation in the study.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Active Comparator

    Arm Label

    SIR-Spheres + Therapy

    Therapy Only

    Arm Description

    SIR-Spheres with Cetuximab + Irinotecan Therapy

    Cetuximab + Irinotecan Therapy

    Outcomes

    Primary Outcome Measures

    Progression Free Survival

    Secondary Outcome Measures

    Full Information

    First Posted
    October 1, 2008
    Last Updated
    December 28, 2012
    Sponsor
    M.D. Anderson Cancer Center
    Collaborators
    Sirtex Medical
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00766220
    Brief Title
    Yttrium Microspheres With Cetuximab Plus Irinotecan for Patients With Advanced Colorectal Cancer Mets to Liver
    Official Title
    Phase II Randomized Study of SIR-Spheres, Yttrium Microspheres With Cetuximab Plus Irinotecan for Patients With Advanced Colorectal Cancer Metastases to the Liver
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2012
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Slow Accrual and withdrawn/exclusion of 2 participants.
    Study Start Date
    October 2009 (undefined)
    Primary Completion Date
    January 2012 (Actual)
    Study Completion Date
    January 2012 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    M.D. Anderson Cancer Center
    Collaborators
    Sirtex Medical

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The goal of this clinical research study is to find out what effects radioactive particles, SIR-spheres, have when injected into the liver, followed by systemic chemotherapy with a combination of cetuximab and irinotecan compared to those who have systemic therapy alone, in patients with colon cancer that has metastasized to the liver. The safety of this treatment and how well it controls the disease will also be studied.
    Detailed Description
    Yttrium microspheres are designed to treat cancer that has metastasized to the liver by giving radiation directly to the tumor. SIR-spheres are designed to deliver radiation directly to the tumor. This radiation kills the tumor cells. Cetuximab is a drug that blocks epidermal growth factor receptor (EGFR). EGFR may be involved in certain types of cancer, including non small-cell lung cancer (NSCLC). When EGFR is stimulated, a series of chemical reactions start that result in a tumor being "told" to grow. Cetuximab tries to stop these reactions by blocking EGFR. This may stop tumors from growing. Irinotecan is designed to block cell growth by blocking an enzyme that repairs DNA, the building blocks of cells. If you agree to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1of 2 groups. Participants in one group will receive the SIR-spheres with Cetuximab and Irinotecan therapy. Participants in the other group will just have the Cetuximab and Irinotecan therapy without the SIR-spheres. There is an equal chance of being assigned to either group. If you are found to be eligible to take part in this study, you will have a blood vessel study (given with x-ray dye) performed. This will help researchers look at the arteries leading to your liver and the surrounding areas. You will receive Versed and Fentanyl, sedative drugs to put you to sleep, intravenously (IV--through a needle in a vein) in your arm. A catheter will be placed through your groin artery into the artery leading to your liver. A catheter is a sterile flexible tube that will be placed into a large artery while you are under local anesthesia and IV sedation. Your physician will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure. X-ray dye will be injected through the catheter. If randomly selected to receive the SIR-Spheres with Cetuximab and Irinotecan therapy, a small amount of radioactive albumin injection (a part of a scan test used to measure the supply of blood through the lungs) will be given to your liver. Images will then be taken to learn if too much of this material (radioactive particles) shows up in your lungs and if your liver anatomy is normal. If everything appears normal, the yttrium microspheres will be given slowly through the catheter in 1 dose. If your liver anatomy is abnormal, the yttrium microspheres will be given slowly through the catheter in 2 doses. After you are given the yttrium microspheres, the catheter will be removed, and pressure will be applied to your groin to stop any bleeding. You will then be monitored for 6 hours to check on your well being. You will be given pain medication, if needed (the same sedative drugs used before). You will be given standard doses of Zantac (ranitidine) to help to protect the stomach during treatment. Chemotherapy with cetuximab and irinotecan will be given on an outpatient basis. A catheter (PICC line, port-a-cath) may be inserted through a vein in your arm or chest to ensure that the chemotherapy is given without interruption. Irinotecan will be given by IV over 90 minutes, once every 3 weeks. Cetuximab will be given once a week. On Day 1 of treatment, you will be given a test dose of cetuximab, to check for any allergic reactions. After that, cetuximab will be given by IV over 2 hours. Before every dose of cetuximab, you will be given a dose of diphenhydramine by IV, to keep from having any allergic reactions. You will also receive medication to prevent nausea, vomiting, or an allergic reaction. You will have a single-photon emission computerized tomography (SPECT) scan within 1 week after your treatment. A SPECT scan lets your doctor study the function of your internal organs. You will have blood (about 2 tablespoons) drawn every week for the first 2 months and then once a month on an outpatient basis. This is so researchers can check the function of your kidneys and liver. You will also have a routine physical exam and a computerized tomography (CT) scan performed once a month to check the growth of your tumor. Researchers will check to see if your tumor is responding to the study treatment by looking at the imaging on CT scans every 8 weeks. You may be taken off this study if your disease gets worse, if you experience intolerable side effects, or if there is not enough of the study drug supply to continue treating your disease. You will be followed-up by telephone for as long as you have cancer. This is an investigational study. Yttrium microspheres are FDA approved for hepatic arterial therapy and treatment of liver metastases. Sir-Sphere therapy has been approved for treating colorectal cancer with liver metastases. The combination of cetuximab and irinotecan is FDA approved for metastatic colorectal cancer. Up to 60 patients will take part in this study. All will be enrolled at M. D. Anderson.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Colon Cancer, Colorectal Cancer
    Keywords
    Colon, Liver, Colorectal cancer, Colorectal cancer metastases to the liver, Metastases to the liver, Colorectal cancer mets to liver, Colon cancer metastasized to liver, Yttrium microspheres, SIR-Spheres, Yttrium-90, Cetuximab, C225, Erbitux, IMC-C225, Irinotecan, CPT-11, Liver directed therapy

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    Participant
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    SIR-Spheres + Therapy
    Arm Type
    Active Comparator
    Arm Description
    SIR-Spheres with Cetuximab + Irinotecan Therapy
    Arm Title
    Therapy Only
    Arm Type
    Active Comparator
    Arm Description
    Cetuximab + Irinotecan Therapy
    Intervention Type
    Drug
    Intervention Name(s)
    SIR-spheres Agent Administration
    Other Intervention Name(s)
    Yttrium-90, Yttrium 90, Yttrium microspheres
    Intervention Description
    SIR-Spheres, resin microspheres containing pure Beta emitter Yttrium-90, given through femoral catheter over 10 minutes.
    Intervention Type
    Drug
    Intervention Name(s)
    Cetuximab
    Other Intervention Name(s)
    C225, Erbitux™, IMC-C225
    Intervention Description
    400 mg/m2 by vein over 2 hours once a week. Cetuximab infusions will be continued weekly at a dose of 250 mg/m2 unless toxicity necessitates interruptions.
    Intervention Type
    Drug
    Intervention Name(s)
    Irinotecan
    Other Intervention Name(s)
    CPT-11
    Intervention Description
    350 mg/m2 (or 300 mg/m2 in patients who are greater or equal to 70 years of age, or have an ECOG PS of 2 or have had prior pelvic and/or abdominal irradiation), by vein over 90 minutes, every three weeks.
    Primary Outcome Measure Information:
    Title
    Progression Free Survival
    Time Frame
    4 Months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients must have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Histology from the hepatic metastasis is not mandatory if the morphological appearances on cross sectional imaging and tumor markers (CEA) are indicative of a colorectal primary. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in two dimensions (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral CT scan. Patients must have radiological evidence of disease progression of disease within 6 months of their most recent dose of chemotherapeutic regimens . Age greater than or equal to 18 years. ECOG performance status less than or equal to 2. Patients must have normal organ and marrow function as defined below within 30 days of receiving the investigational agent: - leukocytes greater than or equal to 3,000/mL - absolute neutrophil count greater than or equal to 1,500/mL - platelets greater than or equal to 100,000/mL - total bilirubin less than or equal to 1.5 times upper limits of normal institutional limits - AST(SGOT) less than or equal to 3 X ULN and ALT(SGPT) less than or equal to 3 X ULN - Creatinine less than or equal to 1.5 times upper limits of normal institutional limits Patients with a prior history of non-colorectal cancer who have no active disease may be eligible if they are disease free for greater than or equal to 12 months prior to treatment. The effects of SIR-Spheres, irinotecan or cetuximab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because radiation as well as other therapeutic agents used in this trial 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 in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign a written informed consent document. Patients without evidence of local disease recurrence from colorectal cancer are eligible Patients with extrahepatic disease confined to the lung is permitted if < 4 lesions are depicted on CTand all are < 3 cm in size Patients with brain mets are eligible for this trial if those patients who have had the area surgically resected or irradiated and have no evidence of active disease as demonstrated by MRI of the brain. Patients must have no evidence of residual neurological dysfunction as per baseline neurological exam. Patients with untreated brain metastases will be considered ineligible. Exclusion Criteria: Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier will be excluded. Patients who have had hepatic external beam radiotherapy will be excluded. Patients may not be receiving any other investigational agents. History of allergic reactions attributed to compounds of similar chemical or biologic composition to SIR-Spheres, irinotecan or cetuximab or other agents used in the study. Evidence of ascites, biopsy proven cirrhosis or portal hypertension suggested by the presence of characteristic imaging features on cross sectional imaging or esophageal varicosities demonstrated on endoscopy or barium swallow. A diagnostic study to rule out the presence of portal hypertension will not be required unless the findings on cross sectional imaging are suggestive but not confirmatory. Hepatic arterial anatomy that would prevent catheterization and the administration of SIR-Spheres into the liver. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring hospital admission or antibiotics,symptomatic congestive heart failure (class III and IV), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations would exclude patients from this study. Contraindications to angiography and selective visceral catheterization: History of severe allergy or intolerance to any contrast media, or atropine. Bleeding diathesis, not correctable by usual forms of therapy that would include medical coagulopathy but not limited to the administration of blood products. Utilization of capecitabine for the 6 weeks preceding SIR-Sphere therapy and indefinitely following SIR-Sphere therapy as per manufacturer's recommendations due to the increased risk of radiation hepatitis. Patients exhibiting the mutant variety for kras will be excluded for participation in the study.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Ravi Murthy, MD
    Organizational Affiliation
    UT MD Anderson Cancer Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Links:
    URL
    http://www.mdanderson.org
    Description
    MD Anderson Cancer Center website

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    Yttrium Microspheres With Cetuximab Plus Irinotecan for Patients With Advanced Colorectal Cancer Mets to Liver

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