Vaccine Treatment for Advanced Non-Small Cell Lung Cancer

NCT00073398 | Completed Phase 1

• 2 other identifiers: NLG010104-C-0049
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This 2-phase study will determine the safety of treating patients with non-small cell lung cancer with the genetically engineered HyperAcute-Lung cancer vaccine. It will establish the proper vaccine dose and will examine side effects and potential benefits of the treatment. The vaccine contains killed lung cancer cells containing a mouse gene that causes the production of a foreign pattern of protein-sugars on the cell surface. It is hoped that the immune response to the foreign substance will stimulate the immune system to attack the patient's own cancer cells that have similar proteins without this sugar pattern, causing the tumor to remain stable or shrink. Patients 18 years of age or older with non-small cell lung cancer that has recurred or no longer responds to standard treatment may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, urinalysis, chest x-rays, and lung function testing. CT, MRI, PET, and ultrasound scans of the chest may be obtained if needed. Participants will receive four vaccinations a month apart from each other. The vaccines will be injected under the skin, similar to the way a tuberculosis skin test is given. Phase I of the study will treat successive groups of patients with increasing numbers of the vaccine cells to evaluate side effects of the treatment and determine the optimum dose. Phase II will look for any beneficial effects of the vaccine given at the highest dose found to be safe in Phase I. Weekly blood samples will be drawn during the 4 months of vaccine treatment. In addition, patient follow-up visits will be scheduled every 2 months for the first year after vaccination and then every 3 months for the next 2 years for the following tests and procedures to evaluate treatment response and side effects:

• Medical history and physical examination
• Blood tests
• X-rays and various scans (nuclear medicine/CT/MRI)
• FACT-L Assessment questionnaire to measure the impact of treatment on the patient's general well-being. The questionnaire is administered before beginning treatment, before each vaccination, and during follow-up visits after completing the treatment. It includes questions on the severity of lung cancer symptoms and the ability to perform normal activities of daily life. In addition to the above procedures, 3 skin punch biopsies will be done at the vaccination site to look for a local immune response. For this procedure, an area of skin is numbed with an anesthetic and a 4 mm (about 1/4-inch) circular area is removed, using a sharp cookie cutter-type instrument. Also, one blood sample per year will be collected for the next 15 years to monitor the safety of the gene transfer. Patients whose lung cancer spreads to the skin, superficial soft tissues, or a superficial lymph node may be asked to undergo a biopsy of the lesion to see what effect the treatment may be having on the tumor.

Conditions

Non-small Cell Carcinoma; Adenocarcinoma of Lung; Squamous Cell Carcinoma; Large Cell Carcinoma; Lung Neoplasms

Keywords

Anti-tumor Vaccination; Alpha (1,3) Galactosyltransferase; Allogeneic Tumor Cells; Hyperacute Lung; NSCLC; Lung Cancer; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and response rate

  Days 57, 85, 127

Study Arms (1)

1

EXPERIMENTAL

Ph II Arm 1

Biological: Drug: Hyperacute Lung Cancer Cell Vaccine

Interventions

Drug: Hyperacute Lung Cancer Cell Vaccine BIOLOGICAL

At dose levels I IV the vaccine cells will be injected intradermally every four weeks for four cycles. Dosage will vary from a total of 3 x 106 to 100 x 106 HyperAcute -Lung Cancer Vaccine cells administered per vaccination cycle. At dose level V patients will receive injections of the HyperAcute -Lung Cancer Vaccine cells to include one (1) initial priming vaccine dose of 500 x 106 cells followed by seven (7) booster vaccine cell doses of 300 x 106 HyperAcute -Lung Cancer cell vaccine cells every two weeks. In Phase II, patients will receive 300 x 106 HyperAcute -Lung Cancer cell vaccine cells every two weeks for a total of 8 doses (4 months).

1

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis of non-small cell lung cancer (NSCLC). Squamous cell (epidermoid), adenocarcinoma, bronchoalveolar carcinoma and large cell anaplastic lung carcinoma histologies are eligible. Mixed histologies of NSCLC (i.e., adenosquamous) are eligible. Mixed NSCLC/small cell lung carcinoma (SCLC), and variant large and small cell lung cancer are NOT eligible for this study.
• Patients being treated at the NCI must have their pathology reviewed and confirmed by the NCI Laboratory of Pathology. Patients being treated at MCG must have their pathology reviewed and confirmed by the MCG Pathology Department.
• Metastatic (AJCC Stage IV- any T, any N, M1), progressive, recurrent or refractory NSCLC. Patients may not be eligible for other curative intent treatment (e.g., surgical resection).
• For the purpose of eligibility for this trial, the above-cited disease states are defined as follows:
• Progressive NSCLC- Defined as increasing measurable disease or the appearance of new measurable disease by RECIST criteria despite treatment.
• Recurrent NSCLC- Defined as the re-appearance of measurable disease or the appearance of new measurable disease by RECIST criteria after prior successful treatment or complete response.
• Refractory NSCLC- Defined as achieving less than a complete response and having residual measurable by RECIST criteria after prior treatment with chemotherapy, targeted or small molecules, monoclonal antibodies or any combination of these.
• Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
• Serum albumin greater than or equal to 3.0 gm/dL.
• Expected survival greater than or equal to 4 months.
• Adequate organ function including:
• Marrow: Hemoglobin greater than or equal to 10.0 gm/dL, absolute granulocyte count (AGC) greater than or equal to 1,000/mm(3) platelets greater than or equal to 100,000/mm(3), absolute lymphocyte count greater than or equal to 475/mm(3).
• Hepatic: Serum total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN) with the exception of less than 2.9 mg/dL for patients with Gilbert's disease, ALT (SGPT) and AST (SGOT) less than or equal to 2.5 times the ULN.
• Renal: Serum creatinine (sCr) less than or equal to 1.5 times the upper limit of normal, or creatinine clearance (Ccr) greater than or equal to 50 mL/min.
• All On-Study Tests must be less than or equal to CTC Grade I toxicity for patients to be eligible for study, excluding serum LDH levels. PT, PTT must be less than or equal to 1.5 times ULN except for patients who are on therapeutic anticoagulant therapy.

You may not qualify if:

• Age less than 18-years-old.
• Active CNS metastases or carcinomatous meningitis.
• Hypercalcemia greater than 2.9 mmol/L, unresponsive to standard therapy (e.g., I.V. hydration, diuretics, calctonin and/or bisphosphate therapy).
• Pregnant or nursing women due to the unknown effects of vaccination on the developing fetus or newborn infant.
• Other malignancy within five years, unless the probability of recurrence of the prior malignancy is less than 5%. Patient's curatively treated for squamous cell carcinoma and basal cell carcinoma of the skin and carcinoma in situ of the uterine cervix (CIN) or patients 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, or current active 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. Subjects who require systemic corticosteroids after beginning vaccinations, will be removed from the study.
• Significant or uncontrolled congestive heart failure (CHF), 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 (Temp. greater than 38.1 degrees C).
• Autoimmune disease (e.g., systemic lupus erythematosis, active rheumatoid arthritis, etc) with the exception of vitiligo. Patients with a remote history of asthma or mild active asthma are eligible.
• Other serious medical conditions that may be expected to limit life expectancy to less than 2-years (e.g., liver cirrhosis).
• Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc).
• A known allergy to any component of the alpha(1,3)galactosyltransferase tumor vaccine or cell lines from which it is derived.
• Patients having undergone splenectomy or prior vaccine therapy for their NSCLC.

Sponsors & Collaborators

• NewLink Genetics Corporation: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Pruitt SK, Kirk AD, Bollinger RR, Marsh HC Jr, Collins BH, Levin JL, Mault JR, Heinle JS, Ibrahim S, Rudolph AR, et al. The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts. Transplantation. 1994 Feb;57(3):363-70. doi: 10.1097/00007890-199402150-00009.

  PMID: 8108871 BACKGROUND

• Lai L, Kolber-Simonds D, Park KW, Cheong HT, Greenstein JL, Im GS, Samuel M, Bonk A, Rieke A, Day BN, Murphy CN, Carter DB, Hawley RJ, Prather RS. Production of alpha-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science. 2002 Feb 8;295(5557):1089-92. doi: 10.1126/science.1068228. Epub 2002 Jan 3.

  PMID: 11778012 BACKGROUND

• Galili U, Shohet SB, Kobrin E, Stults CL, Macher BA. Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol Chem. 1988 Nov 25;263(33):17755-62.

  PMID: 2460463 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Adenocarcinoma of Lung; Carcinoma, Squamous Cell; Carcinoma, Large Cell; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Arun Rajan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2003
• First Posted: November 20, 2003
• Study Start: November 1, 2003
• Primary Completion: November 1, 2012
• Study Completion: March 1, 2013
• Last Updated: May 28, 2020

Record last verified: 2020-05

Locations

US (1)