A Phase II Study of HyperAcute-Lung Cancer Vaccine in Subjects With Advanced Non-Small Cell Lung Cancer Who Responded to First Line Platinum-Doublet Treatment
18 Years
N/A
Both
Carcinoma, Non-Small-Cell Lung
Trial Information
A Phase II Study of HyperAcute-Lung Cancer Vaccine in Subjects With Advanced Non-Small Cell Lung Cancer Who Responded to First Line Platinum-Doublet Treatment
Unfortunately, despite the best clinical efforts and breakthroughs in biotechnology, most
patients diagnosed with advanced stage lung cancer continue to die from their disease.
Reasons for this include that: 1) patients are often diagnosed at a time when their lung
cancer has already spread to other sites such as the chest cavity, bone, lung, liver, and
brain limiting the options for local radiation therapy and surgery, and 2) the cancer cells
are resistant or become resistant to chemotherapy drugs used to treat the patient.
Resistance to one type of chemotherapy agent often rapidly leads to resistance against many
other chemotherapy drugs.
These reasons are the major causes of cancer progression that are usually discussed when
considering treatment options for patients with disease that continues to grow and spread.
However, another important part of the body should be considered-- the immune system.
Scientists have clearly shown that lung cancer cells produce a number of abnormal proteins
or abnormal amounts of certain proteins found in normal lung cells. Normally one would
expect a patient to develop an immune response against these abnormal proteins found in
their cancer and attack them much the way we would fight off an infection from a foreign
bacteria or virus. However, for reasons that scientists do not fully understand, the immune
system fails to respond to these abnormal proteins and does not attack the lung cancer
cells. This human clinical trial proposes a new way to make the immune system recognize the
cancer and encourage it to attack the cancer cells.
Many people are familiar with the idea of transplants between people of organs like the
kidneys or heart. When an organ transplant between two people is completed one of the
problems that can occur is rejection of the donated organ by the recipient. This can occur
because the immune system of the patient who receives the organ attacks the donated organ.
If you were to attempt to transplant a pig heart to a human the rejection would be
dramatically stronger than when organs are transplanted between two people. This is partly
because lower animals express sugar-protein patterns on the surface of their cells that
humans do not. In fact, our immune systems can quickly recognize tissues from lower mammals
such as the pig or the mouse and destroys them.
In this project, we have put a mouse gene into human lung cancer cells that produces these
abnormal sugar patterns and stimulates the immune system to attack the lung cancer. This
strategy works well to kill human other cancer cells in the laboratory, but it needs to be
tried in lung cancer patients to see if it will be effective and to determine if such a
treatment causes any side effects. We propose to test this new treatment in subjects with
non-small cell lung cancer to see if it can stop, slow or destroy tumors in these subjects.
Subjects will be injected with an anti-tumor vaccine consisting of a mixture of three types
of dead human lung cancer cells that have been genetically altered to express the mouse gene
responsible for making this abnormal sugar-protein on the cells.
Inclusion Criteria:
- histological diagnosis of non-small cell lung cancer. Squamous cell (epidermoid),
adenocarcinoma, bronchoalveolar carcinoma and large cell anaplastic lung carcinoma
histologies are eligible. Mixed NSCLC/small cell, and variant large and small are
not eligible.
- AJCC Stage IIIB(pleural effusion) or Stage IV NSCLC
- Subjects must have been previously treated with only a first line platinum-doublet
therapy that may or may not include Avastin(R). Those treated with definitive
chemo-radiation with curative or palliative intent or who have received multiple
regimens are not eligible.
- Subjects' NSCLC must have responded or remained stable through first line
platinum-doublet therapy.
- ECOG Performance Status ≤ 2.
- Serum albumin ≥ 3.0 gm/dL.
- Expected survival ≥ 6 months.
- Hemoglobin ≥ 9.0 g/dl
- Platelets ≥ 100,000 cells/mm3
- ANC ≥ 1500 cells/mm3
- Serum total bilirubin ≤ 2 x ULN, ALT and AST ≤ 2.5 x ULN (≤5 if hepatic metastasis is
present).
- Serum creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 50 ml/min.
- Measurable or non-measurable disease.
- Subjects must have negative serology for HIV prior to entering study.
- Male and female subjects of child bearing potential must agree to use contraception
or avoidance of pregnancy measures while enrolled on study and receiving experimental
drug, and for one month after the last immunization.
Exclusion Criteria:
- Age < 18 years.
- Active CNS metastases or carcinomatous meningitis.
- Subjects' whose NSCLC progressed during/after first line platinum-doublet therapy.
- Subjects having undergone splenectomy.
- Hypercalcemia > 2.9 mmol/L, unresponsive to standard therapy.
- Pregnant or nursing women.
- Other malignancy within the last 5 years, unless the probability of recurrence of the
prior malignancy is < 30%. Patient's curatively treated for squamous and basal cell
carcinoma of the skin and carcinoma in situ of the uterine cervix (CIN) or subjects
with a history of malignant tumor in the past that have been disease free for at
least five years are also eligible for this study.
- History of organ transplant.
- Current, active treatment with immunosuppressive therapy such as cyclosporine,
tacrolimus, etc.
- Subjects taking systemic corticosteroid therapy for any reason including replacement
therapy for hypoadrenalism, are not eligible. Subjects receiving inhaled or topical
corticosteroids are eligible.
- Significant or uncontrolled congestive heart failure, myocardial infarction,
significant ventricular arrhythmias within the last six months or significant
pulmonary dysfunction.
- Active infection or antibiotics within 1-week prior to study, including unexplained
fever.
- Autoimmune disease.
- Any condition, psychiatric or otherwise, that would preclude informed consent,
consistent follow-up or compliance with any aspect of the study.
- A known allergy to any component of the vaccine.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the response rate of the administration of HyperAcute® Lung (HAL) Cancer Vaccine cells by injection into subjects with stage IIIB (pleural effusion) or stage IV non-small cell lung carcinoma who have been treated with first line platinum-dou
Outcome Time Frame:
4 months
Safety Issue:
No
Principal Investigator
Charles J. Link, Jr., M.D.
Investigator Role:
Study Chair
Investigator Affiliation:
NewLink Genetics Corporation
Authority:
United States: Food and Drug Administration
Study ID:
NLG0201
NCT ID:
NCT00420732
Start Date:
January 2007
Completion Date:
December 2013
Related Keywords:
- Carcinoma, Non-Small-Cell Lung
- Carcinoma
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| Northwestern University | Chicago, Illinois 60611 |
| Washington University in St. Louis | St. Louis, Missouri 63110 |
