Tumor Cell Vaccines and ISCOMATRIX With Chemotherapy After Tumor Removal
| Status: | Terminated |
|---|---|
| Conditions: | Skin Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 99 |
| Updated: | 8/5/2017 |
| Start Date: | April 18, 2011 |
| End Date: | July 21, 2016 |
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
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.
- 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.
Background:
Cancer-testis (CT) antigens (CTAs) have emerged as attractive targets for cancer
immunotherapy. Whereas cancers of various histologies exhibit CTA expression, 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 undergoing
complete resection of sarcomas, melanomas, germ cell tumors and epithelial malignancies
metastatic to the lungs, pleura or mediastinum will be vaccinated with autologous tumor cells
exposed ex-vivo to decitabine and radiation following completion of appropriate combined
modality therapy. Vaccines will be administered in conjunction with ISCOMATRIX adjuvant as
well as metronomic oral cyclophosphamide (50 mg PO BID x 7d q 14d), and celecoxib (400 mg PO
BID). Serologic responses to a variety of recombinant CTAs as well as delayed type
hypersensitivity to autologous epigenetically modified tumor cells will be assessed before
and after vaccination.
Primary Objective:
-To assess the safety of an epigenetically modified autologous tumor cell vaccine
administered with ISCOMATRIX adjuvant in combination with metronomic oral cyclophosphamide
and celecoxib in patients undergoing thoracic metastasectomy.
Eligibility:
- Patients with histologically or cytologically proven or clinically evident sarcoma,
melanoma, or epithelial malignancies metastatic to lungs, pleura or mediastinum who can
be rendered no evidence of disease (NED) by metastasectomy.
- Patients must be 18 years or older with an ECOG performance status of 0 2, without
evidence of unstable or decompensated myocardial disease. Patients must have adequate
pulmonary reserve evidenced by FEV1 and DLCO equal to or greater than 30% predicted;
pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG; and be on no
immunosuppressive medications except inhaled corticosteroids at the time vaccination
commences.
- Patients must have a platelet count greater than 100,000, an ANC equal to or greater
than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic
function as evidenced by a total bilirubin of <1.5 x 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) at the time vaccination commences.
Design:
- Patients will undergo thoracic metastasectomy using standard of practice guidelines.
- Portions of the resected tumors will be transferred to the Thoracic Oncology Laboratory.
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 metronomic oral cyclophosphamide and
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 80 patients will be accrued to this trial in order to obtain up to 20
evaluable patients.
Cancer-testis (CT) antigens (CTAs) have emerged as attractive targets for cancer
immunotherapy. Whereas cancers of various histologies exhibit CTA expression, 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 undergoing
complete resection of sarcomas, melanomas, germ cell tumors and epithelial malignancies
metastatic to the lungs, pleura or mediastinum will be vaccinated with autologous tumor cells
exposed ex-vivo to decitabine and radiation following completion of appropriate combined
modality therapy. Vaccines will be administered in conjunction with ISCOMATRIX adjuvant as
well as metronomic oral cyclophosphamide (50 mg PO BID x 7d q 14d), and celecoxib (400 mg PO
BID). Serologic responses to a variety of recombinant CTAs as well as delayed type
hypersensitivity to autologous epigenetically modified tumor cells will be assessed before
and after vaccination.
Primary Objective:
-To assess the safety of an epigenetically modified autologous tumor cell vaccine
administered with ISCOMATRIX adjuvant in combination with metronomic oral cyclophosphamide
and celecoxib in patients undergoing thoracic metastasectomy.
Eligibility:
- Patients with histologically or cytologically proven or clinically evident sarcoma,
melanoma, or epithelial malignancies metastatic to lungs, pleura or mediastinum who can
be rendered no evidence of disease (NED) by metastasectomy.
- Patients must be 18 years or older with an ECOG performance status of 0 2, without
evidence of unstable or decompensated myocardial disease. Patients must have adequate
pulmonary reserve evidenced by FEV1 and DLCO equal to or greater than 30% predicted;
pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG; and be on no
immunosuppressive medications except inhaled corticosteroids at the time vaccination
commences.
- Patients must have a platelet count greater than 100,000, an ANC equal to or greater
than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic
function as evidenced by a total bilirubin of <1.5 x 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) at the time vaccination commences.
Design:
- Patients will undergo thoracic metastasectomy using standard of practice guidelines.
- Portions of the resected tumors will be transferred to the Thoracic Oncology Laboratory.
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 metronomic oral cyclophosphamide and
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 80 patients will be accrued to this trial in order to obtain up to 20
evaluable patients.
- INCLUSION CRITERIA:
INCLUSION CRITERIA PRIOR TO SURGERY (SCREENING CONSENT):
1. Patients with clinically evident or histologically proven 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. NCI Laboratory of Pathology confirmation of diagnosis of sarcomas, melanomas, germ
cell tumors, or epithelial malignancies metastatic to the lungs, mediastinum, or
pleura must have been obtained
3. Patients who were initially rendered NED by surgical resection must remain NED at the
time of treatment.
4. 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.
5. Patients must have an ECOG performance status of 0 2.
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 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.
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 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Click here to add this to my saved trials
