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Tumor Cell Vaccines and ISCOMATRIX With Chemotherapy After Tumor Removal

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01341496
First received: April 22, 2011
Last updated: September 26, 2014
Last verified: September 2014
  Purpose

Background:

- A tumor cell vaccine is an experimental cancer treatment. Cancer cells are collected from a patient and then used to develop a vaccine. The vaccine will produce an immune system response to help destroy other cancer cells in the body. Researchers are studying ways to improve these tumor cell vaccines. One way is to add an adjuvant. An adjuvant is a substance that brings about a stronger immune system response. ISCOMATRIX is an adjuvant that has been used safely in other clinical studies. But it has not been studied with certain tumor cell vaccines. Researchers want to find out whether a tumor cell vaccine with ISCOMATRIX, given along with cancer drug treatment, is a safe and effective way to slow or prevent tumor growth after tumor removal surgery.

Objectives:

- To assess the safety and effectiveness of tumor cell vaccines given with ISCOMATRIX and drug therapy after tumor removal surgery.

Eligibility:

- People at least 18 years of age who have had tumor cell vaccines developed from cells taken from surgically removed tumors.

Design:

  • Patients will be screened with a physical examination, medical history, blood and urine tests, and imaging studies.
  • Patients will be treated with cyclophosphamide (once daily) and celecoxib (twice daily) for 7 days before the first vaccine dose.
  • Patients will receive the tumor cell vaccine once a month for 6 months. They will continue to receive drug therapy throughout the vaccine treatment. Patients will be monitored with regular blood tests and imaging studies.
  • After the first 6 months, patients who have an immune response to the vaccine will continue treatment with the vaccine and chemotherapy. They will also have regular blood tests and imaging studies. They will have this treatment for up to 24 months from the first vaccination or until they no longer have an immune response.
  • Participants will have followup visits for up to 5 years after the first vaccination, or until the tumor returns.

Condition Intervention Phase
Sarcoma
Melanoma
Epithelial Malignancies
Pleural Malignancy
Biological: Epigenetically Modified Autologous Tumor
Drug: Cyclophosphamide
Drug: Celecoxib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Epigenetically-Modified Autologous Tumor Cell Vaccs and ISCOMATRIX(TM) Adjuvant With Metronomic Oral Cyclophosphamide and Celecoxib in Pts Undergoing Resection of Sarcomas, Melanomas, Germ Cell Tumors, or Epithelial Malignancies Metastatic to Lungs, Pleura or Mediastinum

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • tabulation and grade of observed patient toxicities attributed to the vaccine, and report of the fractions of patients who encounter these toxicities at the various grades [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine if 5 or greater of the first 20 vaccinated patients undergoing thoracic metastasectomy have successful tumor cell line development [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
  • Number and characteristics of immunologic responses to a panel of CT antigens in vaccinated patients [ Time Frame: 7 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: April 2011
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
autologous tumor vaccine plus chemotherapy
Biological: Epigenetically Modified Autologous Tumor
5x 10^7 autologous tumor cells emulsified in 0.5 mL ISCOMATRIX adjuvant will be administered IM every 4 weeks for 6 months
Drug: Cyclophosphamide
50 mg PO BID for 7 days prior to the first dose of vaccine and then on days 8 through 14, and 22 through 28 of each 4 week treatment cycle
Drug: Celecoxib
400 mg PO BID for 7 days prior to the first dose of vaccine and then on days 1 through 28 of each 4 week vaccine cycle.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Patients with sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or pleura who can be rendered no evidence of active disease (NED) following standard surgical therapy. Note: Patients with active disease outside the thorax may be eligible for the study once the extrathoracic disease is definitively treated by local modalities such as radiation, surgery, or radiofrequency ablation.
    2. Patients must have received or refused first line standard systemic therapy for their metastases.
    3. Patients with no more than 3 intracranial metastases, which have been definitively treated by surgery or radiation therapy may be eligible for study provided there is no evidence of active disease for at least 2 months.
    4. Patients must have an ECOG performance status of 0 2.
    5. Patients must be 18 years of age or older due to the unknown effects of immunologic responses to germ cell-restricted gene products during childhood and adolescent development.
    6. Seronegative for HIV antibody. Note: The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus may be less responsive to the experimental treatment.
    7. Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
    8. Patients must be aware of the neoplastic nature of their illnesses, the experimental nature of the therapy, alternative treatments, potential benefits, and risks.
    9. Patients must be willing to sign an informed consent and undergo resection of their malignancies at the NCI, to ensure vaccine development.

INCLUSION CRITERIA FOR TREATMENT PHASE OF PROTOCOL (Standard Consent):

  1. Patients must have signed the Screening Consent.
  2. Patients who were initially rendered NED by surgical resection must remain NED at the time of treatment.
  3. Patients with no more than 3 intracranial metastases, which have been definitively treated by surgery or radiation therapy may be eligible for the study, provided there is no evidence of active disease for at least 2 months and no requirement for anticonvulsant therapy or steroids following treatment.
  4. Patients must have an ECOG performance status of 0 2.
  5. Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters:

    Absolute neutrophil count greater than 1500/mm3

    Platelet count greater than 100,000/mm3

    Hemoglobin greater than 8g/dl ( patients may receive transfusions to meet this parameter

    PT within 2 seconds of the ULN

    Total bilirubin < 1.5 x upper limits of normal

    Serum creatin ine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m2.

  6. Seronegative for HIV antibody. Note: The experimental treatment being evaluated in this protocol depends on an intact immune system.

    Patients who are HIV seropositive can have decreased immune competence and thus may be less responsive to the experimental treatment.

  7. Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  8. Patients must be willing to practice birth control during and for four months following treatment.
  9. Patients must be willing to sign the standard informed consent.

EXCLUSION CRITERIA

  1. Patients requiring corticosteroids (other than inhaled) will be excluded.
  2. Patients with life expectancy less than 12 months will be excluded.
  3. Patients receiving warfarin anticoagulation, who cannot be transferred to other agents such as enoxaparin or dabigatran, and for whom anticoagulants cannot be held for up to 24 hours will be excluded.
  4. Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina,decompensated CHF (> NYHA Class II), or myocardial infarctionwithin 6 months of study will be excluded.
  5. Patients with other cardiac diseases may be excluded at the discretion of the PI following consultation with Cardiology consultants.
  6. Patients with any of the following pulmonary function abnormalities will be excluded: FEV, < 30% predicted; DLCO < 30% predicted (post-bronchodilator); pO2 < 60% or pCO2 (Bullet) 50 on room air arterial blood gas.
  7. Pregnant and/or lactating women will be excluded due to the unknown, potentially harmful effects of immune response to CT-X antigens and stem cell proteins that may be expressed in placenta, fetus, and neonates.
  8. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.
  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: NCT01341496

Contacts
Contact: Tricia Kunst, R.N. (301) 451-1233 kunstt@mail.nih.gov
Contact: David S Schrump, M.D. (301) 496-2128 david_schrump@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: David S Schrump, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01341496     History of Changes
Other Study ID Numbers: 110148, 11-C-0148
Study First Received: April 22, 2011
Last Updated: September 26, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Metastatic Cancer
Cancer Vaccine
Immunotherapy
Chest Metastases
Sarcoma
Melanoma

Additional relevant MeSH terms:
Melanoma
Neoplasms
Sarcoma
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Celecoxib
Cyclophosphamide
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2014