ExIST Study of LY2157299 (Galunisertib) in Rectal Cancer
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ClinicalTrials.gov Identifier: NCT02688712 |
Recruitment Status :
Active, not recruiting
First Posted : February 23, 2016
Last Update Posted : January 25, 2024
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Tracking Information | |||||||
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First Submitted Date ICMJE | January 25, 2016 | ||||||
First Posted Date ICMJE | February 23, 2016 | ||||||
Last Update Posted Date | January 25, 2024 | ||||||
Actual Study Start Date ICMJE | March 24, 2016 | ||||||
Estimated Primary Completion Date | December 2025 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Evaluation of pathologic response [ Time Frame: Patients should be evaluated for response at surgery and every 3 months for 2 years and then every 6 months at year three and four. All patients will be followed for survival until death or 5 years post-treatment (whichever comes first) ] Complete response is defined as no viable tumor cells identified.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | ExIST Study of LY2157299 (Galunisertib) in Rectal Cancer | ||||||
Official Title ICMJE | Phase II Study of TGFβ Type I Receptor Inhibitor LY2157299 With Neoadjuvant Chemoradiation in Patients With Locally Advanced Rectal Adenocarcinoma | ||||||
Brief 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 |
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Detailed 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:
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. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Rectal Adenocarcinoma | ||||||
Intervention ICMJE |
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Study Arms ICMJE | Experimental: LY2157299 + Chemoradiation + Surgery
Patients will receive a 14 day course of LY2157299. On day 15 patients will begin chemoradiation treatment with Capecitabine or Fluorouracil. On day 29, patients will undergo another fourteen day course of LY2157299 concurrent with their ongoing chemoradiation treatment. Six to ten weeks after completing their neoadjuvant therapy, patient will undergo a tumor specific mesorectal excision as per standard of care.
Interventions:
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Publications * | Yamazaki T, Gunderson AJ, Gilchrist M, Whiteford M, Kiely MX, Hayman A, O'Brien D, Ahmad R, Manchio JV, Fox N, McCarty K, Phillips M, Brosnan E, Vaccaro G, Li R, Simon M, Bernstein E, McCormick M, Yamasaki L, Wu Y, Drokin A, Carnahan T, To Y, Redmond WL, Lee B, Louie J, Hansen E, Solhjem MC, Cramer J, Urba WJ, Gough MJ, Crittenden MR, Young KH. Galunisertib plus neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a single-arm, phase 2 trial. Lancet Oncol. 2022 Sep;23(9):1189-1200. doi: 10.1016/S1470-2045(22)00446-6. Epub 2022 Aug 8. | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Active, not recruiting | ||||||
Estimated Enrollment ICMJE |
50 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | December 2025 | ||||||
Estimated Primary Completion Date | December 2025 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT02688712 | ||||||
Other Study ID Numbers ICMJE | 15-050A | ||||||
Has Data Monitoring Committee | No | ||||||
U.S. FDA-regulated Product | Not Provided | ||||||
IPD Sharing Statement ICMJE |
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Current Responsible Party | Providence Health & Services | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | Providence Health & Services | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE | Eli Lilly and Company | ||||||
Investigators ICMJE |
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PRS Account | Providence Health & Services | ||||||
Verification Date | January 2024 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |