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Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer

Primary Purpose

Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Vaccine Treatment
Cyclophosphamide
All-trans retinoic acid (ATRA)
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically confirmed metastatic adenocarcinoma of the lung
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1
  • No radiation therapy within 2 weeks of first vaccine administration
  • No chemotherapy within 4 weeks of first vaccine administration
  • No steroid therapy within 4 weeks of first vaccine administration
  • Patient's written informed consent
  • Adequate organ function (measured within a week of beginning treatment)
  • Patients will be tested for human leukocyte antigen A0201 (HLA-A0201) as determined by flow cytometry followed by molecular analysis of a peripheral blood specimen, however this result will not be an inclusion criterion.
  • Measurable metastatic tumor as defined by standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Lesions must be accurately measured in at least one dimension with the longest diameter greater than or equal 20mm. With spiral computer tomography (CT) scan, lesion must be greater than or equal to 10 mm at least one dimension.
  • Patient's must have received, and completed first line chemotherapy.

Exclusion Criteria:

  • Symptomatic brain metastasis
  • Any acute medical problems requiring active intervention
  • Current corticosteroid (other than replacement doses in patients who are hypoadrenal) or other immunosuppressive therapy
  • Any other pre-existing immunodeficiency condition (including known HIV infection)
  • Pregnant or lactating women -- Patients in reproductive age must agree to use contraceptive methods for the duration of the study (*A pregnancy test will be obtained before treatment).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2, 3 or 4

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Combination Immunotherapy

Arm Description

Vaccine + Cytoxan + ATRA as outlined in Detailed Description

Outcomes

Primary Outcome Measures

Number of Evaluable Participants With Tumor Response
Number of participants with evaluable peripheral blood mononuclear cells (PBMCs) who demonstrated sustained tumor peptide-specific T-cell activation after vaccination. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and after each vaccination. T-cell activation profiles were analyzed by ELISpot assay and tested by generalized Wilcoxon for correlation to survival.

Secondary Outcome Measures

Median Time to Progression (TTP)
Analysis of Time to Progression and Survival Endpoints. All patients will be considered in the analysis of progression free survival time (time from start of treatment to progression or death) and survival time (time from initiation of treatment to death). Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Follow-up for this analysis will continue for all patients for their lifetimes. Time to progression and survival probabilities over time will be calculated by the method of Kaplan-Meier.
Median Overall Survival (OS)
Analysis of Time to Progression and Survival Endpoints. All patients will be considered in the analysis of progression free survival time (time from start of treatment to progression or death) and survival time (time from initiation of treatment to death). Follow-up for this analysis will continue for all patients for their lifetimes. Time to progression and survival probabilities over time will be calculated by the method of Kaplan-Meier.
Number of Participants With Serious Adverse Events (SAEs)
Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Criteria (CTAE-3),Version 3.0 (www.ctep.cancer.gov). Particular attention will assess the presence of symptomatic lymphadenopathy or any local skin / soft tissue reaction at the vaccine site. Blood tests for ANA and rheumatoid factor will be performed on any patient who develops evidence of autoimmune phenomena.

Full Information

First Posted
January 19, 2008
Last Updated
May 15, 2013
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Cancer Institute (NCI), National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT00601796
Brief Title
Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer
Official Title
Combination Immunotherapy for Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Cancer Institute (NCI), National Institutes of Health (NIH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to find out what effects (good and/or bad) a tumor vaccine used in combination with two drugs (ATRA and cytoxan) have on the patient and their cancer. We also want to find out if the vaccine and the drugs can boost the patient's immune system and how their immune system reacts, both before and after the vaccine treatment.
Detailed Description
This protocol describes a phase II study involving patients with stage IV adenocarcinoma of the lung. Treatment will consist of Cyclophosphamide (300 mg/m²) to be given IV on day 1 and day 57. On day 4 immunization with intradermal vaccine injections at 4 separate sites (bilateral upper arms and bilateral upper thighs will be repeated every 14 days times 2 followed by every 28 days times 3 (day 4, 18, 32, 60, 88, and 116). Decavac (tetanus shot) 0.5 cc intramuscular (IM) will be given after the first vaccine. ATRA (150 mg/m2/day) oral three times daily (TID) dosing administered after the first and fourth vaccines (day 5-7 & day 61-63). Those patients achieving stable disease (SD), partial response (PR), or complete response (CR) at restaging after the initial 6 vaccines will receive additional vaccines every 3 months until disease progression. The vaccine will consist of GM.CD40L bystander cells admixed with an equivalent number of the 2 allogeneic tumor cell lines. There will be a +/- 7 day window for all study related exams, tests, and procedures.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
adenocarcinoma of the lung, stage IV non-small cell lung cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Combination Immunotherapy
Arm Type
Experimental
Arm Description
Vaccine + Cytoxan + ATRA as outlined in Detailed Description
Intervention Type
Biological
Intervention Name(s)
Vaccine Treatment
Other Intervention Name(s)
Allogeneic Tumor Cell-Based Vaccines
Intervention Description
We created a vaccine in which irradiated allogeneic lung adenocarcinoma cells are combined with a bystander K562 cell line transfected with hCD40L and hGM-CSF. By recruiting and activating dendritic cells, we hypothesized the vaccine would induce tumor regression in metastatic lung adenocarcinoma. Intradermal vaccine was given every 14 days x3, followed by monthly x3.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
cytoxan
Intervention Description
Cyclophosphamide (300 mg/m^2 IV) was administered before 1st and 4th vaccines to deplete regulatory T-cells.
Intervention Type
Drug
Intervention Name(s)
All-trans retinoic acid (ATRA)
Other Intervention Name(s)
Vesanoid®, tretinoin, all trans retinoic acid, ATRA
Intervention Description
All-trans retinoic acid was given (150/mg/m^2/day) after 1st and 4th vaccines to enhance dendritic differentiation.
Primary Outcome Measure Information:
Title
Number of Evaluable Participants With Tumor Response
Description
Number of participants with evaluable peripheral blood mononuclear cells (PBMCs) who demonstrated sustained tumor peptide-specific T-cell activation after vaccination. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and after each vaccination. T-cell activation profiles were analyzed by ELISpot assay and tested by generalized Wilcoxon for correlation to survival.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Median Time to Progression (TTP)
Description
Analysis of Time to Progression and Survival Endpoints. All patients will be considered in the analysis of progression free survival time (time from start of treatment to progression or death) and survival time (time from initiation of treatment to death). Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Follow-up for this analysis will continue for all patients for their lifetimes. Time to progression and survival probabilities over time will be calculated by the method of Kaplan-Meier.
Time Frame
3 years
Title
Median Overall Survival (OS)
Description
Analysis of Time to Progression and Survival Endpoints. All patients will be considered in the analysis of progression free survival time (time from start of treatment to progression or death) and survival time (time from initiation of treatment to death). Follow-up for this analysis will continue for all patients for their lifetimes. Time to progression and survival probabilities over time will be calculated by the method of Kaplan-Meier.
Time Frame
3 years
Title
Number of Participants With Serious Adverse Events (SAEs)
Description
Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Criteria (CTAE-3),Version 3.0 (www.ctep.cancer.gov). Particular attention will assess the presence of symptomatic lymphadenopathy or any local skin / soft tissue reaction at the vaccine site. Blood tests for ANA and rheumatoid factor will be performed on any patient who develops evidence of autoimmune phenomena.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed metastatic adenocarcinoma of the lung Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1 No radiation therapy within 2 weeks of first vaccine administration No chemotherapy within 4 weeks of first vaccine administration No steroid therapy within 4 weeks of first vaccine administration Patient's written informed consent Adequate organ function (measured within a week of beginning treatment) Patients will be tested for human leukocyte antigen A0201 (HLA-A0201) as determined by flow cytometry followed by molecular analysis of a peripheral blood specimen, however this result will not be an inclusion criterion. Measurable metastatic tumor as defined by standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Lesions must be accurately measured in at least one dimension with the longest diameter greater than or equal 20mm. With spiral computer tomography (CT) scan, lesion must be greater than or equal to 10 mm at least one dimension. Patient's must have received, and completed first line chemotherapy. Exclusion Criteria: Symptomatic brain metastasis Any acute medical problems requiring active intervention Current corticosteroid (other than replacement doses in patients who are hypoadrenal) or other immunosuppressive therapy Any other pre-existing immunodeficiency condition (including known HIV infection) Pregnant or lactating women -- Patients in reproductive age must agree to use contraceptive methods for the duration of the study (*A pregnancy test will be obtained before treatment). Eastern Cooperative Oncology Group (ECOG) performance status of 2, 3 or 4
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alberto Chiappori, MD
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-9497
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer

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