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

NCT ID: NCT00601796

Last Updated: 2013-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2012-06-30

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.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination Immunotherapy

Vaccine + Cytoxan + ATRA as outlined in Detailed Description

Group Type: EXPERIMENTAL

Vaccine Treatment

Intervention Type: BIOLOGICAL

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.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide (300 mg/m\^2 IV) was administered before 1st and 4th vaccines to deplete regulatory T-cells.

All-trans retinoic acid (ATRA)

Intervention Type: DRUG

All-trans retinoic acid was given (150/mg/m\^2/day) after 1st and 4th vaccines to enhance dendritic differentiation.

Interventions

Vaccine Treatment

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: BIOLOGICAL

Cyclophosphamide

Cyclophosphamide (300 mg/m\^2 IV) was administered before 1st and 4th vaccines to deplete regulatory T-cells.

Intervention Type: DRUG

All-trans retinoic acid (ATRA)

All-trans retinoic acid was given (150/mg/m\^2/day) after 1st and 4th vaccines to enhance dendritic differentiation.

Intervention Type: DRUG

Other Intervention Names

Allogeneic Tumor Cell-Based Vaccines; cytoxan; Vesanoid®; tretinoin; all trans retinoic acid; ATRA

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alberto Chiappori, MD

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

Other Identifiers

P30CA076292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIH-OBA-0608-801

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-14744

Identifier Type: -

Identifier Source: org_study_id