Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer - Full Text View

Sponsor:	H. Lee Moffitt Cancer Center and Research Institute
Collaborators:	National Cancer Institute (NCI) National Institutes of Health (NIH)
Information provided by (Responsible Party):	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT00601796

Purpose

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.

Condition	Intervention	Phase
Lung Cancer	Biological: Vaccine Treatment Drug: Cyclophosphamide Drug: ATRA	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Combination Immunotherapy for Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Cyclophosphamide Tretinoin

U.S. FDA Resources

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:

Number of Participants With Tumor Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Analysis of Tumor Response. The tumor response rate will be determined. The confidence interval will be determined once the number of evaluable patients is available.

Secondary Outcome Measures:

Time to Progression (TTP) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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 Overall Survival (OS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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 Adverse Events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Criteria (CTAE-3),Version 3.0 (www.ctep.cancer.gov) (Appendix D). 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.

Enrollment:	24
Study Start Date:	October 2006
Estimated Study Completion Date:	March 2012
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Combination Immunotherapy Vaccine + Cytoxan + ATRA as outlined in Detailed Description	Biological: Vaccine Treatment The vaccine will be made by mixing two kinds of cells: 1) some lung cancer cells which have been grown in the lab, and 2) experimental "bystander" cells. All the cells in the vaccine will be treated with high-dose X-rays to make sure that none of them grow and cause more cancer. The bystander cells, called "GM.CD40L", are human cells that have been genetically changed. The original cells, called K562, had the genes for human GM-CSF and CD40L inserted into them. These changes are designed to help boost your immune system to better fight the cancer in your body. GM-CSF is a hormone that is known to stimulate your bone marrow to make more white blood cells. Other Name: Allogeneic Tumor Cell-Based Vaccines Drug: Cyclophosphamide Cytoxan is a commercially available chemotherapy drug that will be given to participants before the vaccines, to try and improve the conditions of their immune system. It is hoped the immune cells that block immune responses will be reduced. Cytoxan will be given on day 1 and day 57. Other Name: cytoxan Drug: ATRA ATRA will change the immune system so that the vaccines will be more effective. ATRA is a tablet (pill), which will be taken 3 times daily for 3 days. Participants will be given the pills to take at home. Participants will take ATRA after their first vaccine and after their fourth vaccine. Other Names: called Vesanoid® tretinoin all trans retinoic acid

Arms

Assigned Interventions

Experimental: Combination Immunotherapy

Vaccine + Cytoxan + ATRA as outlined in Detailed Description

Biological: Vaccine Treatment

The vaccine will be made by mixing two kinds of cells: 1) some lung cancer cells which have been grown in the lab, and 2) experimental "bystander" cells. All the cells in the vaccine will be treated with high-dose X-rays to make sure that none of them grow and cause more cancer. The bystander cells, called "GM.CD40L", are human cells that have been genetically changed. The original cells, called K562, had the genes for human GM-CSF and CD40L inserted into them. These changes are designed to help boost your immune system to better fight the cancer in your body. GM-CSF is a hormone that is known to stimulate your bone marrow to make more white blood cells.

Other Name: Allogeneic Tumor Cell-Based Vaccines

Drug: Cyclophosphamide

Cytoxan is a commercially available chemotherapy drug that will be given to participants before the vaccines, to try and improve the conditions of their immune system. It is hoped the immune cells that block immune responses will be reduced. Cytoxan will be given on day 1 and day 57.

Other Name: cytoxan

Drug: ATRA

ATRA will change the immune system so that the vaccines will be more effective. ATRA is a tablet (pill), which will be taken 3 times daily for 3 days. Participants will be given the pills to take at home. Participants will take ATRA after their first vaccine and after their fourth vaccine.

Other Names:

called Vesanoid®
tretinoin
all trans retinoic acid

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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).
ECOG performance status of 2, 3 or 4

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601796

Locations

United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

National Cancer Institute (NCI)

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Alberto Chiappori, MD

H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT00601796 History of Changes
Other Study ID Numbers:	MCC-14744, P30CA076292, NIH-OBA-0608-801
Study First Received:	January 19, 2008
Last Updated:	September 27, 2011
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

adenocarcinoma of the lung
stage IV non-small cell lung cancer

Additional relevant MeSH terms:

Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Cyclophosphamide
Tretinoin
Immunosuppressive Agents
Immunologic Factors

Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Keratolytic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on February 12, 2012