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

Phase 2

Completed

Conditions: Lung Cancer

Interventions: Biological: Vaccine Treatment
Drug: Cyclophosphamide
Drug: All-trans retinoic acid (ATRA)

Registration Number: NCT00601796

Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination Immunotherapy	All-trans retinoic acid (ATRA)	Vaccine + Cytoxan + ATRA as outlined in Detailed Description
Combination Immunotherapy	Vaccine Treatment	Vaccine + Cytoxan + ATRA as outlined in Detailed Description
Combination Immunotherapy	Cyclophosphamide	Vaccine + Cytoxan + ATRA as outlined in Detailed Description

Primary Outcome Measures

Name	Time	Method
Number of Evaluable Participants With Tumor Response	3 years	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

Name	Time	Method
Median Time to Progression (TTP)	3 years	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)	3 years	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)	3 years	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.