ExIST Study of LY2157299 (Galunisertib) in Rectal Cancer

Rectal Adenocarcinoma Clinical Trial

Official title: Phase II Study of TGFβ Type I Receptor Inhibitor LY2157299 With Neoadjuvant Chemoradiation in Patients With Locally Advanced Rectal Adenocarcinoma

Status Active, not recruiting

Clinical Trial Summary

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

Clinical Trial Description

This is a prospective Phase II study to test the efficacy of LY2157299 in combination with neoadjuvant chemoradiation in patients with rectal adenocarcinoma. This study will test the hypothesis that LY2157299 will improve effector T cell tumor infiltration and activity resulting in improved pathologic response rates. The investigators propose that this improved immune response will result in improved disease-free and overall survival.

The objectives are:

1. Determine the rate of pathologic complete response in patients with locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation and the investigational agent LY2157299

2. Correlate immunoscore changes prior to therapy, during therapy, and at surgical resection with pathologic response and MRI parameters

3. Immune monitoring to evaluate potential biomarkers of treatment success.

Eligible patients will have histologically confirmed rectal adenocarcinoma, AJCC Stage IIA IIIC or AJCC Stage IV appropriate for consideration of primary rectal tumor resection. Patients will undergo a forceps biopsy of the rectal mass as part of the diagnostic workup as well as undergo staging evaluation including an MRI with additional study sequences. Enrolled patients will receive a 14 day course of LY2157299 followed by a repeat biopsy and MRI with study sequences. In this trial the investigators plan to use the maximum tolerated dose of LY2157299 established in human clinical trials, 300mg delivered as 150mg P.O. BID. On day 15 patients will begin chemoradiation with either 5-FU (fluorouracil ) or capecitabine (Xeloda®). On day 29, patients will undergo another fourteen day course of LY2157299 concurrent with their ongoing chemoradiation.

Patients will undergo 50.4 to 54Gy of radiation in 1.8Gy daily fractions delivered Monday through Friday for a total of 28-30 fractions. The acceptable duration of chemoradiation, including treatment breaks or delays, is up to 8 weeks total. Six to ten weeks after completing their neoadjuvant therapy, patient will undergo a tumor specific mesorectal excision as per standard of care with evaluation of pathologic response rate. Patients will be followed for disease-free survival, progression free survival, local recurrence, and overall survival. A three patient safety lead-in will be performed, where a six week safety period following completion of radiation will be completed prior to enrolling subsequent patients. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Rectal Adenocarcinoma
• Rectal Neoplasms

• NCT number: NCT02688712
• Study type: Interventional
• Source: Providence Health & Services
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 24, 2016
• Completion date: December 2025