Phase II Study of TGFβ Type I Receptor Inhibitor LY2157299 with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Adenocarcinoma

The purpose of this study is to see how effective and safe LY2157299, in combination with chemotherapy and radiation therapy, might be in treating rectal cancer. Also as part of this study, research will be done on tumor samples to see if it is possible to predict if patients will respond to treatment, and blood samples to look at the immune system response to study treatment.
About 50 people will take part in this study. The study treatment will be given over an 8 week period and the investigators will continue to collect your health information for up to 5 years, as part of this study

Inclusion Criteria:
• Patients (male and female) with histologically confirmed rectal adenocarcinoma, AJCC Stage IIA-IIIC or AJCC Stage IV appropriate for consideration of primary rectal tumor resection.
• No active bleeding.
• Ability to give informed consent and comply with the protocol. Patients with a history of psychiatric illness must be judged able to understand fully the investigational nature of the study and the risks associated with the therapy.

Exclusion Criteria:
• Active infection requiring systemic antibiotics.
• Active autoimmune disease as defined by the autoimmune disease assessment tool (see protocol)
• Diagnosis of a solid tumor malignancy (excluding non-melanoma skin cancer) within 3 years of enrollment.
• History of prior pelvic radiation.
• Aortic aneurysm (see protocol)
• Abnormal Echocardiogram (see protocol)
• Immunodeficiency, need for immunosuppressive medications, or need for chronic steroids.
• Participation in any investigational drug study within 28 days of enrollment.
• History of cardiac disease, including myocardial infarction within 6 months before study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension, major cardiac abnormalities, a predisposition for developing aneurysms including family history of aneurysms, Marfan syndrome, bicuspid aortic valve, or evidence of damage to the large vessels of the heart.
• Concomitant use of strong CYP3A4 inhibitors and inducers
Phase II
Kristina Young, M.D., Ph.D.
Earle A Chiles Research Institute (EACRI)
Mary Mccormick
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Franz Clinic
  • Providence Cancer Institute Newberg Clinic
  • Providence Portland Medical Center