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

Condition(s) targeted: Lung Cancer

Intervention: GM.CD40L cell vaccine (Drug); allogeneic tumor cell vaccine (Drug); cyclophosphamide (Drug); tretinoin (Drug); flow cytometry (Procedure); immunoenzyme technique (Procedure); immunohistochemistry staining method (Procedure); protein expression analysis (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: H. Lee Moffitt Cancer Center and Research Institute

Official(s) and/or principal investigator(s):
Alberto Chiappori, MD, Principal Investigator, Affiliation: H. Lee Moffitt Cancer Center and Research Institute

RATIONALE: Vaccines made from tumor cells may help the body build an effective immune response to kill tumor cells. Biological therapies, such as tretinoin and cyclophosphamide, may change the immune system in different ways and help the vaccine work better at stop tumor cells from growing.

PURPOSE: This phase II trial is studying how well giving vaccine therapy together with tretinoin and cyclophosphamide works in treating patients with metastatic lung cancer.

Official title: Combination Immunotherapy for Lung Cancer

Study design: Treatment, Open Label

Primary outcome: Tumor response

Secondary outcome:

Time to progression

Survival

Detailed description: OBJECTIVES:

Primary

- To evaluate tumor response rate in patients with stage IV lung cancer receiving vaccine

therapy comprising allogeneic tumor cells and GM. CD40L in combination with tretinoin and cyclophosphamide.

Secondary

- To evaluate patients for the development of specific anti-tumor immune responses after

immunization.

- To quantitate the dendritic cell (DC):immature myeloid cell (ImC) ratio before and after

treatment with tretinoin, vaccine therapy comprising allogeneic tumor cells and GM. CD40L, and cyclophosphamide.

- To evaluate the survival of patients treated with this vaccine.

OUTLINE: Patients receive cyclophosphamide IV on days 1 and 57, vaccine (formulated by mixing allogeneic tumor cells and GM. CD40L) intradermally at 4 separate sites on days 4, 18, 32, 60, 88, and 116, and oral tretinoin three times daily on days 5-7 and days 61-63 in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease, partial response, or complete response receive the vaccine every 3 months until disease progression.

Patients undergo blood collection periodically during treatment for immune response testing, including determination of dendritic cell (DC):immature myeloid cell (ImC) ratios by flow cytometry and ELISPOT analysis. Archived diagnostic biopsy tissue is analyzed for the expression of WT1, CEA, and hTERT by immunohistochemistry.

After completion of study treatment, patients are followed periodically.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the lung

- Metastatic disease

- Measurable metastatic tumor as defined by standard RECIST criteria

- Lesions must be accurately measured in at least 1 dimension with the longest

diameter ≥ 20 mm (≥ 10 mm in at least 1 dimension by spiral CT scan)

- Completed first-line chemotherapy

- No symptomatic brain metastases

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- WBC > 3,000/mm³

- ANC > 1,500/mm³

- Platelets > 100,000/mm³

- Hematocrit > 25%

- Bilirubin < 2. 0 mg/dL

- Creatinine < 2. 0 mg/dL OR creatinine clearance > 60 mL/min

- No acute medical problems requiring active intervention

- No other pre-existing immunodeficiency condition (including known HIV infection)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No radiotherapy 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

- No concurrent corticosteroids (other than replacement doses in patients who are

hypoadrenal) or other immunosuppressive therapy

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa, Florida 33612-9497, United States; Recruiting
Clinical Trials Office - H. Lee Moffitt Cancer Center and Rese, Phone: 800-456-7121, Email: canceranswers@moffitt.org

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: October 2006
Last updated: October 8, 2008