Lung CancerPhase 1/2NCT00534209
Vaccine Therapy in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy
A Phase 1/2 study testing Allogeneic B7.1/HLA-A1 in people with Lung Cancer, run by University of Miami at 2 sites in United States.
Trial summary
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. PURPOSE: This randomized phase I/II trial is studying the side effects of vaccine therapy and to see how well it works in treating patients with stage IIIB or stage IV non-small cell lung cancer who… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Allogeneic B7.1/HLA-A1
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2009to Apr 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with stage IIIB (non-candidates for radiation) or stage IV pathologically confirmed non-small cell carcinoma of the lung that completed 4-6 cycles of platinum based first line chemotherapy and achieved complete response (CR), partial response (PR) or stable disease.
- Last administration of chemotherapy occurred no later than 4 weeks prior to the enrollment date.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Renal Requirements: The calculated creatinine clearance must be at least 50 ml/min.
- Pulmonary Function Requirements:
- All patients will undergo evaluation of pulmonary function prior to enrollment.
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- Patients should have a Forced expiratory volume in 1 second (FEV1) more than 30% of the predicted value and/or Diffusing capacity (DLCO) more than 30% of the predicted value with a partial pressure of carbon dioxide (PCO2) < 45mm.
- Any patient enrolled in the protocol whose respiratory symptoms have experienced marked deterioration not related to a known cause (e.g. pneumonia, congestive heart failure (CHF) or pulmonary embolism (PE)) will have request pulmonary function test (PFT) evaluation and if the above parameters are seen will be excluded from the protocol.
- Age ≥ 18 years.
- Signed informed consent.
- Patients should have absolute neutrophil count (ANC) ≥ 1000/mm3; platelets (PLT) ≥ 80,000/mm3.
Who cannot join
- Small cell carcinoma of the lung.
- Existing autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren's disease etc; colitis, inflammatory bowel disease or pancreatitis within 10 years of study.
- Other active malignancies present within the past three years, except for basal and/or squamous cell carcinoma(s) or in situ cervical cancer.
- Concomitant steroid or other immunosuppressive therapy.
- Active infection, or less than 7 days since therapy for acute infections.
- Pericardial effusion.
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- Currently receiving chemotherapy for another condition (such as arthritis).
- Time elapsed greater than 4 weeks since last administration of first line chemotherapy for NSCLC.
- Active or symptomatic cardiac disease such as congestive heart failure, angina pectoris or recent myocardial infarction.
- Pregnant or lactating women (negative test for pregnancy required of women of childbearing potential).
- Refusal in fertile men or women to use effective birth control measures during and for six months after the completion of treatment on study.
- Known HIV infection
- Untreated or uncontrolled brain metastasis.
- Liver Enzymes greater than 3 times the institutional upper limit.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Memorial Regional Hospital
Hollywood, Florida, 33021
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
About this study
Official title: Phase I/II Clinical Trial of Immunotherapy With an Allogeneic B7.1/HLA-A1 Transfected Tumor Cell Vaccine in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer That Have Completed First Line Chemotherapy
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells.
PURPOSE: This randomized phase I/II trial is studying the side effects of vaccine therapy and to see how well it works in treating patients with stage IIIB or stage IV non-small cell lung cancer who have finished first-line chemotherapy.
Read the detailed description
OUTLINE: This is a multicenter study.
- Phase I (single site [University of Miami Sylvester Comprehensive Cancer Center]): Patients receive allogeneic B7.1 and human leukocyte antigen-A1 (HLA-A1) transfected tumor cell vaccine intradermally (ID) in weeks 1, 3, and 5. Treatment repeats every 6 weeks for 2 courses. If no more than 1 of 6 patients experience a probable or definitively treatment related adverse effect (i.e., grade 2 autoimmune or grade 3-4 of any type), patients proceed to the phase II portion of the study. If 2 or more (out of 6) patients experience treatment related adverse effects the study stops.
- Phase II (randomized): Patients are stratified according to study site (University of Miami Sylvester Comprehensive Cancer Center or Memorial Regional Hospital), type of prior first-line treatment (platinum and taxane vs platinum and gemcitabine), and presence of brain metastasis (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive allogeneic B7.1 and HLA-A1 transfected tumor cell vaccine ID in weeks 1, 3, and 5. Treatment repeats every 6 weeks for 2 courses.
- Arm II: Patients receive a placebo vaccine as in arm I. Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for cluster of differentiation 8 (CD8), cluster of differentiation 4 (CD4), and natural killer cell (NK) response and peripheral blood lymphocytes (PBL) and T helper cell 1 (TH1)/T helper cell 2 (TH2) bias, including levels of interleukin (IL) IL-1β, IL-2, IL-4, IL-5, IL-6, IL-13, Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) via ELISA.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 4 years, and then once a year thereafter.
PROJECTED ACCRUAL: A total of 66 patients (6 patients for phase I and 60 patients for phase II) will be accrued for this study.
- Conditions
- Lung Cancer
- Being tested
- Allogeneic B7.1/HLA-A1, Placebo
- Keywords
- stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic B7.1/HLA-A1Biological
Also called - B7.1, - B7, - Ad100-B45-Neo-B7.1-HLA A1 or HLA2
Dose: At least 4x10^7 irradiated HLA/B7.1 transfected AD100 cells Given intradermally
PlaceboOther
Given intradermally
| Study group | Role | What they receive |
|---|---|---|
| Arm I: Allogeneic B7.1/HLA-A1 | Experimental | Patients will receive Allogeneic B7.1/HLA-A1 vaccine once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines.
Given intradermally. Receives: Biological: Allogeneic B7.1/HLA-A1 |
| Arm II: Placebo | Placebo comparator | Patients receive a placebo vaccine intradermally once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preliminary Safety Profile (Phase 1)
This will include the number of patients experiencing toxicity over the course of treatment, characterized by type of toxicity and grade, and by the time of toxicity onset in relation to day of vaccination.
Measured: Up to 13 weeks
Progression-free Survival (Phase 2)
Measured: Date of randomization to the earliest date of documented progression.
Secondary outcomes (6)
Immune Response (CD8) in B7-vaccinated Participants as Compared to Controls. (Phase 2)
Rate of immune response (CD8) in B-7 vaccinated participants reported for measurements taken immediately prior to vaccination (week 0) and throughout the two courses.
Measured: About 13 weeks
Relationship of CD8 Response in B7-vaccinated Patients to Their Progression-free Survival.(Phase 2)
Relationship of CD8 response in B7-vaccinated patients to their progression-free survival. Summarized by the median and range of follow up time for patients grouped according to disease status (progression/no progression) and vital status (died/alive at last contact).
Measured: From Week 1 of Study Therapy until Death or Withdrawal of Consent
Safety Profile (Phase 2)
The rate of patients experiencing toxicity over the course of treatment will be characterized by type of toxicity and grade, and by the time of toxicity onset in relation to day of vaccination.
Measured: About 13 weeks
Response to Second-line Chemotherapy After Disease Progression (Phase 2)
The percentage of patients experiencing a clinical response (complete response (CR), partial response (PR), stable disease (SD)) on second-line chemotherapy will be characterized for B7-vaccinated patients and controls.
Measured: From Week 1 of Study Therapy until Death or Withdrawal of Consent
Overall Survival (Phase 2)
The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that study participants are still alive.
Measured: Date of randomization to the recorded date of death
Correlative Immunological Studies in Study Participants (Phase 2)
The time course of patients' adaptive immune response to B7 vaccination as compared to control vaccine will be characterized by their CD8, CD4, and NK response (measured by ELI-spots for interferon-gamma (IFN-γ), interleukin 4 (IL-4), and granzyme B secretion) measured prior to vaccination (i.e. at baseline) and over two courses of vaccination (measurements at week 7 and 13).
Measured: Baseline, Week 7 and Week 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2007 (estimated)
- Study startJan 2009
- Primary completionApr 2010
- Study completionApr 2010
Why it stopped: Per request of Principal Investigator this study was closed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Luis E. Raez, MD, FACP, Study chair, University of Miami Sylvester Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00534209
- Sponsor's protocol ID
- 20057158
- Other IDs
- SCCC-2005042, WIRB-20051678
- Status last verified
- Sep 2017
- First submitted
- 20 Sep 2007
- Last updated
- 16 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Raez LE, Cassileth PA, Schlesselman JJ, Padmanabhan S, Fisher EZ, Baldie PA, Sridhar K, Podack ER. Induction of CD8 T-cell-Ifn-gamma response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma. Cancer Gene Ther. 2003 Nov;10(11):850-8. doi: 10.1038/sj.cgt.7700641.
PubMed 14605671Frankowski DJ, Raez J, Manners I, Winnik MA, Khan SA, Spontak RJ. Formation of dispersed nanostructures from poly(ferrocenyldimethylsilane-b-dimethylsiloxane) nanotubes upon exposure to supercritical carbon dioxide. Langmuir. 2004 Oct 12;20(21):9304-14. doi: 10.1021/la049646l.
PubMed 15461522
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Clinical Trial of Immunotherapy With an Allogeneic B7.1/HLA-A1 Transfected Tumor Cell Vaccine in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer That Have Completed First Line Chemotherapy
- ClinicalTrials.gov ID
- NCT00534209
- Acronym / sponsor ID
- 20057158
- Conditions
- Lung Cancer
- Keywords
- stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Per request of Principal Investigator this study was closed.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- Jan 2009 (actual)
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 24 Sep 2007 (estimated)
- Results
- Posted 20 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells.
PURPOSE: This randomized phase I/II trial is studying the side effects of vaccine therapy and to see how well it works in treating patients with stage IIIB or stage IV non-small cell lung cancer who have finished first-line chemotherapy.
Detailed description
OUTLINE: This is a multicenter study.
- Phase I (single site [University of Miami Sylvester Comprehensive Cancer Center]): Patients receive allogeneic B7.1 and human leukocyte antigen-A1 (HLA-A1) transfected tumor cell vaccine intradermally (ID) in weeks 1, 3, and 5. Treatment repeats every 6 weeks for 2 courses. If no more than 1 of 6 patients experience a probable or definitively treatment related adverse effect (i.e., grade 2 autoimmune or grade 3-4 of any type), patients proceed to the phase II portion of the study. If 2 or more (out of 6) patients experience treatment related adverse effects the study stops.
- Phase II (randomized): Patients are stratified according to study site (University of Miami Sylvester Comprehensive Cancer Center or Memorial Regional Hospital), type of prior first-line treatment (platinum and taxane vs platinum and gemcitabine), and presence of brain metastasis (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive allogeneic B7.1 and HLA-A1 transfected tumor cell vaccine ID in weeks 1, 3, and 5. Treatment repeats every 6 weeks for 2 courses.
- Arm II: Patients receive a placebo vaccine as in arm I. Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for cluster of differentiation 8 (CD8), cluster of differentiation 4 (CD4), and natural killer cell (NK) response and peripheral blood lymphocytes (PBL) and T helper cell 1 (TH1)/T helper cell 2 (TH2) bias, including levels of interleukin (IL) IL-1β, IL-2, IL-4, IL-5, IL-6, IL-13, Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) via ELISA.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 4 years, and then once a year thereafter.
PROJECTED ACCRUAL: A total of 66 patients (6 patients for phase I and 60 patients for phase II) will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I: Allogeneic B7.1/HLA-A1 | Experimental | Biological: Allogeneic B7.1/HLA-A1Patients will receive Allogeneic B7.1/HLA-A1 vaccine once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines. Given intradermally. |
| Arm II: Placebo | Placebo comparator | Other: PlaceboPatients receive a placebo vaccine intradermally once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with stage IIIB (non-candidates for radiation) or stage IV pathologically confirmed non-small cell carcinoma of the lung that completed 4-6 cycles of platinum based first line chemotherapy and achieved complete response (CR), partial response (PR) or stable disease.
- Last administration of chemotherapy occurred no later than 4 weeks prior to the enrollment date.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Renal Requirements: The calculated creatinine clearance must be at least 50 ml/min.
- Pulmonary Function Requirements:
Key exclusion criteria (14 listed)
- Small cell carcinoma of the lung.
- Existing autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren's disease etc; colitis, inflammatory bowel disease or pancreatitis within 10 years of study.
- Other active malignancies present within the past three years, except for basal and/or squamous cell carcinoma(s) or in situ cervical cancer.
- Concomitant steroid or other immunosuppressive therapy.
- Active infection, or less than 7 days since therapy for acute infections.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogeneic B7.1/HLA-A1Also: - B7.1, - B7, - Ad100-B45-Neo-B7.1-HLA A1 or HLA2Dose: At least 4x10^7 irradiated HLA/B7.1 transfected AD100 cells Given intradermally | Biological | Arm I: Allogeneic B7.1/HLA-A1 |
| PlaceboGiven intradermally | Other | Arm II: Placebo |
Primary outcome
Preliminary Safety Profile (Phase 1)
Time frame: Up to 13 weeks
This will include the number of patients experiencing toxicity over the course of treatment, characterized by type of toxicity and grade, and by the time of toxicity onset in relation to day of vaccination.
Progression-free Survival (Phase 2)
Time frame: Date of randomization to the earliest date of documented progression.
6 secondary outcomes
Immune Response (CD8) in B7-vaccinated Participants as Compared to Controls. (Phase 2)
Time frame: About 13 weeks
Relationship of CD8 Response in B7-vaccinated Patients to Their Progression-free Survival.(Phase 2)
Time frame: From Week 1 of Study Therapy until Death or Withdrawal of Consent
Safety Profile (Phase 2)
Time frame: About 13 weeks
Response to Second-line Chemotherapy After Disease Progression (Phase 2)
Time frame: From Week 1 of Study Therapy until Death or Withdrawal of Consent
Overall Survival (Phase 2)
Time frame: Date of randomization to the recorded date of death
Correlative Immunological Studies in Study Participants (Phase 2)
Time frame: Baseline, Week 7 and Week 13
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14605671Raez LE, Cassileth PA, Schlesselman JJ, Padmanabhan S, Fisher EZ, Baldie PA, Sridhar K, Podack ER. Induction of CD8 T-cell-Ifn-gamma response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma. Cancer Gene Ther. 2003 Nov;10(11):850-8. doi: 10.1038/sj.cgt.7700641.
- Background: PubMed 15461522Frankowski DJ, Raez J, Manners I, Winnik MA, Khan SA, Spontak RJ. Formation of dispersed nanostructures from poly(ferrocenyldimethylsilane-b-dimethylsiloxane) nanotubes upon exposure to supercritical carbon dioxide. Langmuir. 2004 Oct 12;20(21):9304-14. doi: 10.1021/la049646l.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luis E. Raez, MD, FACP study chair
University of Miami Sylvester Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Allogeneic B7.1/HLA-A1 in people with Lung Cancer, run by University of Miami at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Preliminary Safety Profile (Phase 1) (time frame: Up to 13 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00534209, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2017.