Active8 Trial in Head and Neck Cancer
Everyone in the study will begin treatment with the same, standard-of-care treatment (consisting of a combination of cisplatin or carboplatin + 5 fluorouracil + cetuximab) that a patient would normally receive if he/she were not in the study. The only treatment difference in this study is that some patients will receive the standard-of-care treatment AND motolimod and others will receive the standard-of-care treatment AND a placebo (an injection that does not contain active drug).
Active8 is a clinical study for patients with recurrent or metastatic squamous cell cancer of the head and neck (SCCHN). This study is evaluating whether motolimod, when used in combination with an FDA-approved regimen that includes chemotherapy and a monoclonal antibody, mobilizes a patient's own natural defenses to attack head and neck cancer that has presented in an advanced state or has returned after previous treatment. Approximately 175 men and women will participate in the trial at more than 50 centers throughout the United States. For more information about the location of an open center near you, please go to www.clinicaltrials.gov.
The primary objective of the study is to compare whether motolimod added to the standard treatment of cetuximab, 5-fluorouracil (5-FU) and platinum chemotherapy will result in a decrease in tumor growth and if it helps patients with SCCHN live longer when compared to the same standard treatment without motolimod. Researchers also want to evaluate the side effects of the combination of standard treatment and motolimod.
Active8 is a randomized, double-blind, placebo-controlled study of chemotherapy plus cetuximab in combination with motolimod in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. This means that neither a patient nor his/her doctor will know whether the patient is receiving motolimod or a placebo along with his/her standard therapy (cetuximab, platinum and 5-FU chemotherapy).
Cetuximab plus a combination chemotherapy regimen that includes a platinum agent (carboplatin or cisplatin) and 5-fluorouracil (5-FU) was approved by the FDA as a standard treatment regimen in locally advanced or metastatic squamous cell carcinoma of the head and neck. In prior studies, patients who received this regimen experienced a delay in time before the cancer worsened (e.g., the time until the tumor grew) by an average of five and a half months (Vermorken, et al. New England Journal of Medicine, 2008). Doctors hope that the addition of motolimod to this FDA-approved regimen will result in a decrease in tumor growth and help patients live longer.
Preclinical data with motolimod has demonstrated enhanced killing of SCCHN cells in combination with cetuximab, and improved antitumor effects in combination with some chemotherapies. The combination of motolimod plus cetuximab is being evaluated in a study of 13 patients. So far the evidence indicates that the two drugs can be given together without too many serious side effects.
About Head and Neck Cancer
Head and neck cancer refers to a group of different types of malignancies that develop in the head and neck area, including in the ears, nose, mouth, and throat. These cancers behave very differently depending on the area in which they first develop, called the primary tumor site. They can also look very different when examined under a microscope, with several subtypes of cancer seen. The most common subtype (or histology) of cancer that develops in the head and neck area is squamous cell carcinoma, which grows from the mucous cells lining the surfaces inside of the nose, mouth, and throat. These cancers are often referred to collectively as squamous cell carcinomas of the head and neck (SCCHN).
Since SCCHN tumors can be quite variable, depending on the location of the primary tumor and the extent of spread of the disease, your doctors will perform an extensive evaluation to determine the extent of the cancer and the best treatment options available. These treatment options may include local therapy such as surgery or radiation, or may include systemic (oral or injected) treatments such as chemotherapy. Targeted therapies such as monoclonal antibodies or immunotherapy may also be used. For tumors which are relatively small, confined to one area, or appear less aggressive, local therapy may be all that is needed. However, if the cancer is large or has spread to other areas (metastasized), more treatment is often needed.
Understanding Locally Advanced or Metastatic Disease
The head and neck is an extremely complex part of the body, with many different types of tissues and important structures. Unfortunately, sometimes when a tumor is diagnosed, the extent of disease makes it impossible to operate and remove the cancer. This is referred to as locally advanced or metastatic disease. Sometimes a tumor which has been treated with surgery or with radiotherapy with the intent to cure will return, either in the same area or in another part of the body. This is referred to as recurrent disease. In both of these settings, systemic therapy is generally required to treat the cancer.