Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 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:
NCT01143545
First received: June 11, 2010
Last updated: May 3, 2014
Last verified: April 2014
  Purpose

Background:

- Certain types of lung, esophageal, or thymic cancers and mesotheliomas have specific antigens (protein molecules) on their surfaces. Research studies have shown that giving a vaccine that contains antigens similar to these may cause an immune response, which may keep tumors from growing. Researchers are also interested in determining whether the chemotherapy drug cyclophosphamide and the anti-inflammatory drug celecoxib may help the vaccine work better, particularly in patients with lung cancer.

Objectives:

- To evaluate the safety and effectiveness of tumor cell vaccines in combination with cyclophosphamide and celecoxib in patients with cancers involving the chest.

Eligibility:

- Individuals at least 18 years of age who have had surgery for small cell or non-small cell lung cancer, esophageal cancer, thymoma or thymic carcinoma, and malignant pleural mesothelioma.

Design:

  • Following recovery from surgery, chemotherapy, or radiation, participants will have leukapheresis to collect lymphocytes (white blood cells) for testing.
  • Participants will receive celecoxib and cyclophosphamide to take twice a day at home, 7 days before the vaccine.
  • Participants will have the vaccine in the clinical center (one or two shots per month for 6 months), and will stay in the clinic for about 4 hours after the vaccine. Participants will keep a diary at home of any side effects from the vaccine, and will continue to take cyclophosphamide and celecoxib.
  • One month after the sixth vaccine, participants will provide another blood sample for testing, and if the tests are satisfactory will return to the clinic every 3 months for 2 additional vaccines.
  • Participants will return to clinic for follow-up physical examinations, lab tests, and scans every 3 months for 2 years and then every 6 months for up to 3 years.

Condition Intervention Phase
Lung Cancer
Esophageal Cancer
Malignant Pleural Mesothelioma
Sarcoma
Thymic Carcinoma
Biological: Allogeneic Tumor Cell Vaccine (K562)
Drug: Celecoxib
Drug: cyclophosphamide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib as Adjuvant Therapy for Lung and Esophageal Cancers, Thymic Neoplasms, Thoracic Sarcomas, and Malignant Pleural Mesotheliomas

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Tabulation of toxicity type and grade [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To ascertain if K526-GM vaccines induce immunity to CT antigens commonly expressed in thoracic malignancies. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To determine if metronomic oral CP and celecoxib reduce the number, percentage and function of CD4+ CD25+ Fox P3+ regulatory T cells (T reg) in peripheral blood of thoracic oncology patients. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: May 2010
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Allogeneic tumor cell vaccine + chemotherapy
Biological: Allogeneic Tumor Cell Vaccine (K562)
Subcutaneous injection monthly for 6 months
Drug: Celecoxib
400 g po bid
Drug: cyclophosphamide
50 mg po bid

  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 primary small cell or non-small cell lung cancer, esophageal cancer, thymoma, thymic carcinoma, primary sarcoma of the chest, or pleural mesothelioma with no evidence of disease (NED) or minimal residual disease (MRD) in the primary site following standard multi-modality therapy.
  2. Patients must be evaluated within 52 weeks following completion of standard therapy and have shown no evidence of disease during that time.
  3. Patients with intracranial metastases, which have been treated by surgery or radiation therapy may be eligible for study provided there is no evidence of active disease and no requirement for anticonvulsant therapy or steroids following treatment.
  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. 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 times upper limits of normal
    • Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2).
  7. 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.
  8. 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.
  9. Patients must be willing to practice birth control during and for four months following treatment.
  10. Patients must be willing to sign an informed consent.
  11. Patients must be willing to sign an informed consent.

EXCLUSION CRITERIA:

  1. Patients who are initially rendered NED or MRD by combined modality therapy but exhibit disease progression prior to initiation of vaccination will be excluded from the study.
  2. Patients who will have received more than two systemic cytotoxic treatment regimens for their thoracic malignancy by the time vaccination commences will be excluded.
  3. Patients requiring corticosteroids (other than inhaled) will be excluded.
  4. Patients with life expectancy less than 12 months will be excluded.
  5. 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.
  6. Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated CHF (> NYHA Class II), or myocardial infarction within 6 months of study will be excluded.
  7. Patients with other cardiac diseases may be excluded at the discretion of the PI following consultation with Cardiology consultants.
  8. Patients with any of the following pulmonary function abnormalities will be excluded: FEV, < 30% predicted; DLCO < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air.
  9. 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.
  10. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.
  11. Patients with any type of primary immunodeficiencies will be excluded from the study.
  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: NCT01143545

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: NCT01143545     History of Changes
Other Study ID Numbers: 100138, 10-C-0138
Study First Received: June 11, 2010
Last Updated: May 3, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cancer Vaccine
Immunotherapy
Adjuvant Therapy
Surgical Intervention
Lung Cancer
Esophageal Cancer
Thymic Carcinoma
Malignant Pleural Mesothelioma

Additional relevant MeSH terms:
Mesothelioma
Carcinoma
Esophageal Neoplasms
Lung Neoplasms
Neoplasms, Mesothelial
Thymoma
Thymus Neoplasms
Sarcoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenoma
Neoplasms, Complex and Mixed
Lymphatic Diseases
Neoplasms, Connective and Soft Tissue
Cyclophosphamide
Celecoxib
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 27, 2014