Back to results

Vaccine Therapy in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy

Primary Purpose

Lung Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Allogeneic B7.1/HLA-A1

Placebo

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA

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.
- 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.

EXCLUSION CRITERIA:

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.
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.

Sites / Locations

Memorial Regional Hospital
University of Miami Sylvester Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I: Allogeneic B7.1/HLA-A1

Arm II: Placebo

Arm Description

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.

Patients receive a placebo vaccine intradermally once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines.

Outcomes

Primary Outcome Measures

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.

Progression-free Survival (Phase 2)

Secondary Outcome Measures

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.

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).

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.

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.

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.

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).

Full Information

NCT ID

NCT00534209

First Posted

September 20, 2007

Last Updated

September 14, 2017

Sponsor

University of Miami

1. Study Identification

Unique Protocol Identification Number

NCT00534209

Brief Title

Vaccine Therapy in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Terminated

Why Stopped

Per request of Principal Investigator this study was closed.

Study Start Date

January 2009 (Actual)

Primary Completion Date

April 2010 (Actual)

Study Completion Date

April 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Miami

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Cancer

Keywords

stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I: Allogeneic B7.1/HLA-A1

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm II: Placebo

Arm Type

Placebo Comparator

Arm Description

Patients receive a placebo vaccine intradermally once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines.

Intervention Type

Biological

Intervention Name(s)

Allogeneic B7.1/HLA-A1

Other Intervention Name(s)

- B7.1, - B7, - Ad100-B45-Neo-B7.1-HLA A1 or HLA2

Intervention Description

Dose: At least 4x10^7 irradiated HLA/B7.1 transfected AD100 cells Given intradermally

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Given intradermally

Primary Outcome Measure Information:

Title

Preliminary Safety Profile (Phase 1)

Description

Time Frame

Up to 13 weeks

Title

Progression-free Survival (Phase 2)

Time Frame

Date of randomization to the earliest date of documented progression.

Secondary Outcome Measure Information:

Title

Immune Response (CD8) in B7-vaccinated Participants as Compared to Controls. (Phase 2)

Description

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.

Time Frame

About 13 weeks

Title

Relationship of CD8 Response in B7-vaccinated Patients to Their Progression-free Survival.(Phase 2)

Description

Time Frame

From Week 1 of Study Therapy until Death or Withdrawal of Consent

Title

Safety Profile (Phase 2)

Description

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.

Time Frame

About 13 weeks

Title

Response to Second-line Chemotherapy After Disease Progression (Phase 2)

Description

Time Frame

From Week 1 of Study Therapy until Death or Withdrawal of Consent

Title

Overall Survival (Phase 2)

Description

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.

Time Frame

Date of randomization to the recorded date of death

Title

Correlative Immunological Studies in Study Participants (Phase 2)

Description

Time Frame

Baseline, Week 7 and Week 13

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA 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. 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. EXCLUSION CRITERIA: 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Luis E. Raez, MD, FACP

Organizational Affiliation

University of Miami Sylvester Comprehensive Cancer Center

Official's Role

Study Chair

Facility Information:

Facility Name

Memorial Regional Hospital

City

Hollywood

State/Province

Florida

ZIP/Postal Code

33021

Country

United States

Facility Name

University of Miami Sylvester Comprehensive Cancer Center

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

14605671

Citation

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.

Results Reference

background

PubMed Identifier

15461522

Citation

Frankowski 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.

Results Reference

background

Learn more about this trial

Vaccine Therapy in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy

We'll reach out to this number within 24 hrs