Clinical Trials /

GVAX for Colorectal Cancer

NCT01952730

Description:

This study is a Pilot clinical trial. Pilot clinical trials test the safety of an investigational combination of drugs. Pilot studies provide information on what effects, both good and bad, the Investigational agent might have on your disease. "Investigational" means that the intervention is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not approved the treatment for your type of cancer. The main purposes of this study are to determine: - The amount of vaccine that can be made for your colorectal tumor cells - If the vaccine can be given safely - What the effects of the vaccine are, both good and bad - How the vaccine affects your immune system - Whether this vaccine might have any effect on the return of your cancer in the liver after surgical removal This study is being done because there are currently no treatments which have demonstrated to cure diseae which has progressed, or moved beyond the site of the primary site of disease (colon or rectum). These vaccinations will be given after you have completed the standard of care treatment as determined by your doctor. Laboratory research has made vaccines from cancer cells by inserting genetic material from a protein called granulocyte-macrophage colony stimulating factor (GM-CSF) into the cancer cell. Once complete, the cancer cells are able to produce large amounts of GM-CSF. The vaccine made form these cells has a greater anti-tumor effect than cancer cells without GM-CSF. The purpose of this research study is to determine the safety of an investigational vaccine that will be made using your own colorectal cancer cells in the manner described above. This vaccine has been used in several other research studies for treatment for other cancers (skin, lung, ovarian, sarcoma and leukemia.) Information from these other research studies suggests that this vaccine may help to reduce the risk of your colorectal cancer returning after you have your colorectal cancer surgery. Due to these results in melanoma and several other tumors we are encouraged to use this vaccine approach in patients with liver metastases from colorectal cancer, after the cancer in the liver has been removed by surgery.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: GVAX for Colorectal Cancer
  • Official Title: A Pilot Safety Study of Vaccination With Autologous, Lethally Irradiated Colorectal Cancer Cells Engineered by Adenoviral Mediated Gene Transfer to Secrete Human Granulocyte-Macrophage Stimulating Factor

Clinical Trial IDs

  • ORG STUDY ID: 12-436
  • NCT ID: NCT01952730

Conditions

  • Colorectal Cancer

Interventions

DrugSynonymsArms
GVAXExperimental Treatment Arm

Purpose

This study is a Pilot clinical trial. Pilot clinical trials test the safety of an investigational combination of drugs. Pilot studies provide information on what effects, both good and bad, the Investigational agent might have on your disease. "Investigational" means that the intervention is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not approved the treatment for your type of cancer. The main purposes of this study are to determine: - The amount of vaccine that can be made for your colorectal tumor cells - If the vaccine can be given safely - What the effects of the vaccine are, both good and bad - How the vaccine affects your immune system - Whether this vaccine might have any effect on the return of your cancer in the liver after surgical removal This study is being done because there are currently no treatments which have demonstrated to cure diseae which has progressed, or moved beyond the site of the primary site of disease (colon or rectum). These vaccinations will be given after you have completed the standard of care treatment as determined by your doctor. Laboratory research has made vaccines from cancer cells by inserting genetic material from a protein called granulocyte-macrophage colony stimulating factor (GM-CSF) into the cancer cell. Once complete, the cancer cells are able to produce large amounts of GM-CSF. The vaccine made form these cells has a greater anti-tumor effect than cancer cells without GM-CSF. The purpose of this research study is to determine the safety of an investigational vaccine that will be made using your own colorectal cancer cells in the manner described above. This vaccine has been used in several other research studies for treatment for other cancers (skin, lung, ovarian, sarcoma and leukemia.) Information from these other research studies suggests that this vaccine may help to reduce the risk of your colorectal cancer returning after you have your colorectal cancer surgery. Due to these results in melanoma and several other tumors we are encouraged to use this vaccine approach in patients with liver metastases from colorectal cancer, after the cancer in the liver has been removed by surgery.

Detailed Description

      After you have given your consent to participate in this study, your study doctor will
      perform some tests to confirm that you are eligible to participate. These tests may take
      place up to 21 days before the surgery to remove a liver tumor, which will be used to create
      the vaccines. Many of the following examinations are commonly done to determine diagnosis
      and/or stage of disease and you may have already had some or all of these evaluations. They
      may or may not have to be repeated. These tests include a medical history, performance
      status, blod samples, routine blood tests, tumor assessment and blood pregnancy test (if
      applicable). If these tests indicate you are eligible for this study and you agree to
      participate, you will be referred to a surgeon for the surgical removal of tumor tissue from
      which the vaccine will be made.

      The surgery will be performed at Massachusetts General Hospital. You will be asked to sign a
      separate consent form to give permission to the surgeon to perform this operation. That
      consent will describe the risks of the operation which involves removing the tumor cells
      from your liver.

      After your surgery, there is a possibility that your physician will recommend other
      treatment before starting the vaccines if he or she feels it would be beneficial to your
      care and medically appropriate. This part of the treatment would not be experimental (for
      example, chemotherapy or radiation therapy).

      Then, in this case, the vaccines made from your cancer will not be administered to you until
      at least 4 weeks after your last chemotherapy or radiation treatment. If the time between
      your operation and the first scheduled vaccine injection is 8 weeks or longer, we will ask
      you to undergo another chest, abdomen and pelvic CT scan and clinical blood work to confirm
      that it is still safe for you to proceed with the vaccines. After this 4 week rest period,
      vaccine administration will occur as previously outlined.

      If these tests indicate you are eligible for this study and you agree to participate, you
      will be referred to a surgeon for the surgical removal of tumor tissue from which the
      vaccine will be made.

      It is important to know that sometimes we are unable to collect enough cells from the tumor
      collection. In those cases we can try to grow the tumor cells for a short period of time to
      get enough cells to make a vaccine, but we can not guarantee that we will always be able to
      produce vaccine for every participant who undergoes tumor cell collection.

      The vaccines created from your colorectal cancer cells are scheduled to be given to you on
      days 1, 8, 15 and then every two weeks after that until 6 total vaccines have been
      administered. The amount of vaccines is dependent on the total amount of cells collected
      when your colorectal cancer liver metastasis is processed and prepared into vaccine in our
      lab. It is hoped that you will receive at least six vaccines. All scheduled treatment will
      occur in the outpatient clinic.

      The vaccines will be administered in two injections that will be placed underneath your
      skin. The two injections will be given at the same place on your body. The recommended sites
      are your arms, thighs or trunk area and the sites will rotate per vaccine.

      Day 1 is the first day of treatment on study. The following procedures are planned on this
      day: update of medical history, physical exam, blood samples for routine labs, required
      blood sample for immune studies, vaccine administration, and, if enough cells can be grown,
      you will receive an injection of cancer cells that have been killed but not able to secrete
      GM-CSF. This is done to measure the amount of reaction of your immune system caused by the
      vaccine alone.

      Punch biopsies will be obtained 2 days after the first and fifth vaccinations. A DTH
      injection will also be administered at the first and fifth vaccine. Two days after the
      vaccine and DTH administration punch biopsy will be taken. DTH injections are Delayed-type
      Hyper-sensitivity Tests. This injection inserts a small amount of the vaccine under your
      skin to determine if you have any allergic reactions to the vaccine. This will consist of a
      small piece of skin tissue removed under local anesthesia. A small stitch will be placed
      after the biopsy. You will sign a separate consent form for this procedure.

      The following procedures are planned for Days 8 and 15: update of medical history, weight
      and vital signs, blood samples for routine labs and immune studies, and vaccine
      administration.

      On day 29 and every two weeks (until no more vaccines are available) you wil undergo an
      update of medical history, physical exam, weight and vital signs, blood samples for routine
      labs and immune studies, punch biopsy and vaccine administration. With vaccine #5, you may
      receive a second DTH injection. Two days after the vaccine and DTH injection, punch biopsies
      will be taken off both sites to further evaluate your body's response to the treatment.

      After the final dose of study drug, your treating physician will determine if you are
      eligible to receive a second series of vaccinations. In addition, there must be sufficient
      numbers of cells for vaccine remaining from the original harvest or a new liver metastasis
      has occurred and been removed to make more vaccine.

      If you give consent to participate in the repeat dose phase, you will be required to repeat
      the screening tests to see if you are still eligible to participate in the study.

      It is possible that additional rounds of vaccine therapy may be offered after the second
      round, as long as it is appropriate in the opinion of your treating physician and additional
      tumor is available to make vaccine and you continue to meet the eligibility criteria.

      Participants will be monitored every 3 months with a blood test for the first 3 years and
      then every 6-12 months for a total of 5 years. Staging CT scans will be performed 3 months
      after the last vaccination, then every 6 months for the first three years and then yearly to
      year 5. After 5 years imaging will be at the discretion of the treating physician. Blood
      draws for immune research studies will occur every 3 months for 2 years after completing all
      vaccinations.
    

Trial Arms

NameTypeDescriptionInterventions
Experimental Treatment ArmExperimentalGVAX, up to 6 vaccinations, administered via injection

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically documented hepatic colorectal cancer metastasis with resectable
                 hepatic lesions
    
              -  At least 4 weeks since last dose of chemotherapy, radiotherapy, immunotherapy,
                 systemic glucocorticoid therapy or operation in order to receive vaccine
    
              -  Fully recovered from hepatic resection
    
            Exclusion Criteria:
    
              -  Pregnant or breastfeeding
    
              -  Uncontrolled active infection
    
              -  Infection with HIV, Hepatitis B or C
    
              -  Other current malignancies except in situ cancer or basal/squamous cell carcinoma
    
              -  Active autoimmune disease
    
              -  Hepatic metastases involving both branches of the portal vein or all three hepatic
                 veins
    
              -  Peritoneal metastases identified at the time of attempted resection
    
              -  Greater than 1 month since resection of liver metastasis for vaccine production
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:number of patients who fail to receive the first six scheduled vaccinations because of toxicity
    Time Frame:2 years
    Safety Issue:
    Description:To determine the safety of 6 vaccinations with lethally irradiated, autologous colorectal cancer cells engineered by adenoviral mediated gene transfer to secrete GM-CSF in stage IV colorectal cancer patients who are completely resected. Patient safety will be assured by monitoring the number of patients who fail to receive the first six scheduled vaccinations because of toxicity. If three or more patients experience grade 4 or worse toxicity due to the vaccine before completing six immunizations, the study will be terminated.

    Secondary Outcome Measures

    Measure:Progression Free Survival
    Time Frame:10 years
    Safety Issue:
    Description:To determine the progression free survival of stage IV colorectal cancer patients vaccinated with lethally irradiated, autologous colorectal cancer cells engineered by adenoviral mediated gene transfer to secrete GM-CSF.
    Measure:Immune Response
    Time Frame:2 years
    Safety Issue:
    Description:To evaluate the immune response elicited by the vaccine. We will evaluate the immune cell composition(CD4+ and CD8+ T cells, T regulatory cells, macrophage, etc) in the resected specimens and in the circulating blood.
    Measure:Two year survival
    Time Frame:5 years
    Safety Issue:
    Description:To assess overall survival at 2 years

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Suspended
    Lead Sponsor:Massachusetts General Hospital

    Trial Keywords

    • Stage IV
    • Hepatic Lesions

    Last Updated

    November 17, 2016