A Phase I Study of AZD6244 in Combination With Capecitabine and Radiotherapy in Locally Advanced Adenocarcinoma of the Rectum

Background:

• The investigational anti-cancer drug Selumetinib (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.

Objectives:

• To determine safe and effective doses of AZD6244, along with radiation and chemotherapy, to treat rectal cancer.

Eligibility:

• 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.

Design:

• 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.