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Epigenetically-Modified Autologous Tumor Cell Vaccines With ISCOMATRIX(TM) Adjuvant and Oral Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thoracic Sarcomas, and Malignant Pleural Mesotheliomas


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Mesolthelioma, Esophageal Cancer, Lung Cancer

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Trial Information

Epigenetically-Modified Autologous Tumor Cell Vaccines With ISCOMATRIX(TM) Adjuvant and Oral Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thoracic Sarcomas, and Malignant Pleural Mesotheliomas


Background:

- Cancer-testis (CT) antigens have emerged as attractive targets for cancer
immunotherapy. Whereas lung and esophageal cancers, primary thoracic sarcomas, as well
as malignant pleural mesotheliomas express a variety of CT antigens, primary or
vaccine-induced immune responses to these antigens appear uncommon in patients with
these malignancies, possibly due to low-level, heterogeneous antigen expression, and
inadequate vaccination strategies.

- Because numerous CT antigens can be induced in tumor cells by DNA demethylating agents
and HDAC inhibitors, it is conceivable that vaccination of cancer patients with
autologous tumor cells exposed to chromatin remodeling agents will enhance anti-tumor
immunity in these individuals.

- In order to examine this issue, patients with resectable primary neoplasms involving
the lungs, esophagus, or pleura will be vaccinated with autologous tumor cells exposed
exvivo to decitabine and radiation following completion of appropriate combined
modality therapy. Vaccine will be administered in conjunction with
ISCOMATRIX(Trademark) adjuvant and oral celecoxib.

Primary Objective:

- To assess the safety of an epigenetically modified autologous tumor cell vaccine in
conjunction with celecoxib.

Eligibility:

- Patients with histologically or cytologically proven primary pulmonary carcinoma or
sarcoma, esophageal cancer, or malignant pleural mesothelioma undergoing resection of
their neoplasms.

- Patients must be 18 years or older with an ECOG performance status of 0 - 2, with
adequate pulmonary and cardiac function and laboratory values within normal limits.

Design:

- Patients with operable lung and esophageal carcinoma/sarcoma, or malignant pleural
mesothelioma will undergo resection of their malignancies at the NCI.

- Portions of the resected tumors will be transferred to the Thoracic Oncology Laboratory
and cells will be processed to establish a cancer cell line.

- Following recovery from surgery and appropriate adjuvant chemotherapy and/or radiation,
patients will be vaccinated with epigenetically-modified autologous tumor cells
periodically over 6 months in conjunction with oral celecoxib.

- Systemic toxicities and delayed type hypersensitivity responses to autologous tumor
cells and serologic responses to a variety of CT antigens will be assessed before and
after vaccination.

- Patients will be followed with routine staging scans until disease recurrence.

- As the exact set of comparisons and analyses to be performed will be determined
following completion of the trial, and will be based on limited numbers of patients,
the analyses will be considered exploratory and hypothesis generating rather than
definitive.

- Approximately 120 patients will be accrued to this trial in order to obtain up to 30
evaluable patients.

Inclusion Criteria


- ELIGIBILITY CRITERIA:

INCLUSION CRITERIA PRIOR TO SURGERY (SCREENING CONSENT):

1. Patients with resectable primary small cell or non-small cell lung cancers,
esophageal cancers, primary sarcoma of the chest, or pleural mesotheliomas are
eligible for treatment.

2. 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.

3. Patients with prior Decitabine exposure are eligible for study.

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/mm(3)

- Platelet count greater than 100,000/mm(3)

- 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 creatin ine less than or equal to 1.6 mg/ml or the creatinine clearance
must be greater than 70 ml/min/1.73M(2).

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 FOR TREATMENT PHASE OF PROTOCOL:

1. Patients unable/unwilling to undergo resection of their malignancies at the NCI will
be excluded.

2. Patients who are initially rendered NED by combined modality therapy but exhibit
disease progression prior to initiation of vaccination will be excluded from the
treatment portion of the study.

3. Patients who will have received more than two systemic cytotoxic treatment regimens
for their thoracic malignancy by the time vaccination commences will be excluded.

4. Patients requiring corticosteroids (other than inhaled) will be excluded.

5. Patients with life expectancy less than 12 months will be excluded.

6. 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.

7. 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.

8. Patients with other cardiac diseases may be excluded at the discretion of the PI
following consultation with Cardiology consultants.

9. Patients with any of the following pulmonary function abnormalities will be excluded:
FEV, < 30% predicted; DLCO < 30% predicted (post-bronchodilator); pO2 < 60% or
pCO2 greater than or equal to 50 on room air arterial blood gas.

10. 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.

11. Patients with active infections, including HIV, will be excluded, due to unknown
effects of the vaccine on lymphoid precursors.

12. Patients with any type of primary immunodeficiencies will be excluded from the study.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety of the tumor cell vaccine administered with ISCOMATRIX(TM) adjuvant and oral celecoxib.

Outcome Time Frame:

3 years

Safety Issue:

Yes

Principal Investigator

David S Schrump, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

110041

NCT ID:

NCT01258868

Start Date:

December 2010

Completion Date:

December 2017

Related Keywords:

  • Mesolthelioma
  • Esophageal Cancer
  • Lung Cancer
  • Mesothelioma
  • Esophageal Cancer
  • Lung Cancer
  • Thoracic Malignancies
  • Tumor Cell Vaccine
  • Esophageal Diseases
  • Esophageal Neoplasms
  • Lung Neoplasms
  • Mesothelioma

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892