Track topics on Twitter Track topics that are important to you
- The investigational anti-cancer drug AZD6244 prevents a protein found in rectal cancer from working properly, which may slow tumor growth and allow radiation and chemotherapy treatments to destroy more cancer cells. Researchers are interested in determining whether AZD6244 can be used to improve treatment outcomes in individuals who have rectal cancer that has spread outside the rectum into the surrounding pelvis.
- To determine safe and effective doses of AZD6244, along with radiation and chemotherapy, to treat rectal cancer.
- Individuals at least 18 years of age who have been diagnosed with rectal cancer that has spread outside the inner wall of the rectum or into lymph nodes in the pelvis.
- Eligible participants will be screened with a physical examination, blood and tumor samples, and imaging studies.
- Participants will receive AZD6244 twice a day by mouth for 1 full week (7 days) before starting radiation and chemotherapy and every week thereafter until the end of the radiation and chemotherapy treatment.
- Participants will have radiation therapy daily, 5 days per week, for approximately 6 weeks.
- Participants will receive chemotherapy (capecitabine) twice daily, 5 days per week, for approximately 6 weeks.
- Approximately 4 to 8 weeks after completing the AZD6244, radiation, and chemotherapy treatment, participants may have surgery to remove any tumors and affected lymph nodes. This surgery is not part of the treatment delivered on this protocol.
- Participants will have a follow-up exam 3 weeks after the end of treatment, every 3 months for the first year, and then in the second and third year after the end of treatment. These visits will involve a full medical examination and imaging studies.
- Local recurrences of rectal cancer are morbid and difficult to manage effectively.
- Colorectal cancers frequently harbor RAS mutations and EGF/EGFR over-expression.
- AZD6244 is an orally available selective, adenosine triphosphate-uncompetitive inhibitor of MEK1/2 that sensitizes tumor cells to radiation in vitro and in vivo.
- To define the maximum tolerable dose of AZD6244 Hyd-Sulfate delivered BID, 7 days per week, in combination with radiation therapy (RT) and Capecitabine in patients with locally advanced adenocarcinoma of the rectum without distant metastases.
- To define the dose-limiting toxicities and toxicity profile associated with administration of AZD6244 Hyd-Sulfate delivered BID, 7 days per week in combination with RT and Capecitabine
- To evaluate the pharmacokinetics of AZD6244 delivered alone and in combination with Capecitabine 825 mg/m(2) PO BID.
- To obtain exploratory information regarding the pathologic response rate obtained after treatment with the MTD of AZD6244 Hyd-Sulfate in combination with Capecitabine and 50.4 Gy of RT.
- To determine if changes in phosphorylated ERK (pERK) in peripheral blood mononuclear cells correlates to changes in pERK in rectal tumors in the setting of treatment with AZD6244.
- To perform an exploratory analysis to determine if the presence of activating mutations in RAS or BRAF in tumor or changes in plasma transforming growth factor-alpha (TGFalpha) levels and tumor pERK/total ERK with AZD6244 treatment alone and after AZD6244 in combination with Capecitabine and RT predicts for down staging or pathologic response.
- Histologically or cytologically confirmed locally advanced, non-metastatic adenocarcinoma of the rectum (clinical stage T3AnyN, T4AnyN, or AnyTN+).
- Age greater than or equal to 18 years.
- ECOG performance status less than or equal to 2.
- Normal organ and marrow function.
- All patients will receive 50.4 Gy of RT to the pelvis and rectal tumor delivered concurrently with Capecitabine and AZD6244. AZD6244 will be delivered BID daily, 7 days per week, in a dose escalated fashion. AZD6244 will begin one week prior to Capecitabine and RT and will conclude on the last day of Capecitabine and RT.
- Capecitabine will be delivered at 825 mg/m(2) PO every 12 hours, 5 days per week, starting on the first day of RT and continuing until the last day of RT.
- Biopsies of tumor tissue will be obtained prior to treatment, after one week of AZD6244, and after one week of AZD6244, RT, and Capecitabine for correlative assays.
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Non-Metastatic Adenocarcinoma of the Rectum
Radiation Therapy, Capecitabine, AZD6244
National Institutes of Health Clinical Center, 9000 Rockville Pike
National Institutes of Health Clinical Center (CC)
Published on BioPortfolio: 2014-08-27T03:13:16-0400
The purpose of this study is to assess the effect and safety of AZD6244 (ARRY-142886)versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-lin...
The purpose of the study is to assess if there is benefit when using AZD6244 in the treatment if metastatic colorectal cancer in comparison with another treatment called capecitabine. Thi...
RATIONALE: Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop...
The primary objective of this pilot study is to determine whether neoadjuvant capecitabine/oxaliplatin/cetuximab and external beam radiation therapy followed by surgical resection [and the...
This research study is designed to see if Capecitabine and Lenvatinib in combination with external radiation therapy are effective in treating locally advanced rectal adenocarcinoma in pat...
Local recurrence is a common failure pattern in adenocarcinoma of the cecum. This study aimed to investigate the potential role of adjuvant radiation therapy on oncologic outcomes of patients with ade...
Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II s...
Toxicity, Tolerability, and Compliance of Concurrent Capecitabine or 5-Fluorouracil in Radical Management of Anal Cancer With Single-dose Mitomycin-C and Intensity Modulated Radiation Therapy: Evaluation of a National Cohort.
Chemoradiation therapy (CRT) with mitomycin C (MMC) and 5-fluorouracil (5-FU) is established as the standard of care for the radical treatment of patients with anal squamous cell carcinoma (ASCC). The...
Pyridoxine, an activated form of vitamin B6 used to treat allergic dermatitis, may prevent capecitabine-associated hand-foot syndrome (HFS), although evidence of the benefit of prophylactic pyridoxine...
To compare outcomes in patients receiving neoadjuvant stereotactic body radiation therapy (SBRT) with those receiving intensity-modulated radiation therapy (IMRT) for pancreatic adenocarcinoma.
Preliminary cancer therapy (chemotherapy, radiation therapy, hormone/endocrine therapy, immunotherapy, hyperthermia, etc.) that precedes a necessary second modality of treatment.
Organs which might be damaged during exposure to a toxin or to some form of therapy. It most frequently refers to healthy organs located in the radiation field during radiation therapy.
An estrogen responsive cell line derived from a patient with metastatic human breast ADENOCARCINOMA (at the Michigan Cancer Foundation.)
Drugs used to protect against ionizing radiation. They are usually of interest for use in radiation therapy but have been considered for other, e.g. military, purposes.
A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases.
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...