Protocol Number: 99-C-0142

Title:

Phase II Trial of Individualized Mutant p53 Peptide-Pulsed Cultured Autologous Dendritic Cells in the Adjuvant Treatment of Patients with Locally Advanced Non-Small Cell Lung Cancer After Standard Therapy

Number:

99-C-0142

Summary:

This study will evaluate the effect of a specially tailored vaccine to treat patients with non-small cell lung cancer. About 50 to 60 percent of patients with this type of cancer have a defective gene called p53, which produces a protein that protects their tumor from attack by the immune system. The vaccine is designed to stimulate the immune system to recognize the tumor cells and kill them.

The faulty p53 gene can cause various types of abnormalities that result in runaway growth of cancer cells. Each patient's vaccine will be custom matched to their specific p53 abnormality. After completing standard treatment--which may include chemotherapy, radiation and surgery--patients will be infused with the vaccine once a week for five weeks. Patients whose tumors respond to the treatment may receive additional vaccinations at two-month intervals for as long as they continue to benefit. In a previous small study, five out of five patients showed an immune response to p53 peptide vaccination.

Candidates for the study will be screened with a medical history, blood and urine tests and imaging studies (X rays and CT scans). A tumor sample will also be taken to see if it has a p53 abnormality suitable for this study. Study patients will undergo apheresis-a procedure to collect white blood cells needed to make their vaccine. In apheresis, blood is drawn through a needle in one arm, similar to donating blood. The blood goes through a machine that separates out some of the white cells, and the rest of the blood is returned, usually through a needle in the other arm. Patients will also have additional physical exams, blood tests, and imaging studies during the course of the study to evaluate the effects of treatment.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

NOTE: all of these criteria must be confirmed within 4 weeks of initial vaccination and be confirmed prior to genetic screening for p53 mutations

INCLUSION CRITERIA:

Histologic diagnosis of non-small cell lung cancer.

AJCC stage IIIA or IIIB NSCLC except for patients with pleural effusions. Patients with significant pleural effusions are excluded from this study.

Patients must have completed or plan to undergo a form of curative-intent therapy for their lung cancer. Curative intent therapy is defined as at least two cycles of preoperative chemotherapy for resectable patients with known N2 or N3 disease or at least 55 Gy radiation with concomitant or sequential chemotherapy for patients judged to be unresectable. For patients found to have incidental N2 or N3 disease at time of surgery (disease not detected with staging evaluation prior to definitive surgery) adjuvant chemotherapy and radiation therapy are optional.

Eastern Cooperative Oncology Group PS 0-1.

Ability to give informed consent.

Adequate organ function including:

Renal: serum creatinine less than 2.5 mg/dl;

Marrow: total lymphocyte count greater than 475/mm(3), total granulocytes greater than 1000/mm(3), and platelets greater than 100,000/mm(3);

Hepatic: Serum total bilirubin less than 2.0 mg/dl, SGOT less than 3.0 x normal.

Submission of pathology specimen(s) for screening for one of the following types of p53 mutations: point mutation altering the protein sequence or a frame shift mutation with the generation of a novel sequence.

EXCLUSION CRITERIA:

HIV positivity, or history of Hepatitis C virus infection or active Hepatitis B virus infection due to their known effects on the immune response.

Significant pleural effusion defined as a pleural effusion visible on plain chest radiograph (whether or not cytology is positive for malignancy).

Pregnancy or breast feeding.

Other malignancies within five years, unless the probability of recurrence from prior malignancy is less than 5%. Patients who have had a malignant tumor in the past and have been disease free for at least five years are also eligible for this study.

A condition, psychiatric or otherwise, that would preclude consistent follow-up or compliance with any component of the study.

Myocardial infarction or significant ventricular arrhythmias within the last six months.

Any other serious medical condition that limits life expectancy to less than 2 years.

Hypercalcemia (serum calcium greater than or equal to 11.0 mg/dl (2.75 mmol) corrected for serum albumin).

Serum albumin less than 3.0 gm/dL.

Any serious ongoing infection.

An allergy to eggs will not exclude a patient from this study. However, patients with egg allergies will not undergo influenza vaccination.

Special Instructions: Currently Not Provided

Keywords:

Dendritic Cells

Mutant p53

Non-Small Cell Lung Cancer

Locally Advanced

Vaccination

Recruitment Keywords:

Lung Cancer

Conditions:

Non-Small-Cell Lung Carcinoma

Investigational Drug(s):

Mutant p53 Peptides

IL-4

CD40L

Investigational Device(s):

None

Contacts:

Wendy Gao, R.N.
National Institutes of Health
Building 10
Room 4N115
10 Center Drive
Bethesda, Maryland 20892
Phone: (301) 402-1898
Fax: (301) 402-1001

Electronic Address: gaowe@mail.nih.gov

Citations:

p53: a frequent target for genetic abnormalities in lung cancer

Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer Lung Cancer Study Group

ras gene mutations in non-small cell lung cancers areassociated with shortened survival irrespective of treatment intent

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