ExIST Study of LY2157299 (Galunisertib) in Rectal Cancer

NCT02688712 | Active Not Recruiting Phase 2

• 1 other identifier: 15-050A
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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

Conditions

Rectal Adenocarcinoma

Keywords

IIA; Xeloda; radiation therapy; LY2157299; tumor resection; capecitabine; 5FU; Fluorouracil; IIB; IIC; IV; neoadjuvant; Rectal cancer; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Evaluation of pathologic response

  Complete response is defined as no viable tumor cells identified.

  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)

Secondary Outcomes (3)

• Immunoscore (utilizing tumor tissue)

  Screening Visit, Day 15 Visit and Day of Surgery

• MRI Parameters

  Screening Visit and Day 15 Visit

• Immunologic monitoring parameters

  Days 1, 15, 22, 29, 43, 57 Visits, and Day of Surgery.

Study Arms (1)

LY2157299 + Chemoradiation + Surgery

EXPERIMENTAL

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.

Drug: LY2157299; Drug: Capecitabine; Drug: Fluorouracil; Procedure: Tumor specific mesorectal excision

Interventions

LY2157299 DRUG

Small molecule inhibitor of transforming growth factor-beta signaling pathway

Also known as: Galunisertib

LY2157299 + Chemoradiation + Surgery

Capecitabine DRUG

Antimetabolite chemotherapy

Also known as: Xeloda

LY2157299 + Chemoradiation + Surgery

Fluorouracil DRUG

Antimetabolite chemotherapy

Also known as: 5-fluorouracil , 5-FU, Adrucil, Efudex, Fluoroplex

LY2157299 + Chemoradiation + Surgery

Tumor specific mesorectal excision PROCEDURE

Tumor specific mesorectal excision

LY2157299 + Chemoradiation + Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Age 18 years or above.
• Laboratory values (performed within 28 days prior to enrollment) as follows:
• WBC ≥3.0 109/L
• Hgb ≥9g/dl (patients may be transfused to reach this level)
• Platelets ≥99 109 /L
• Creatinine ≤1.5X upper limit of laboratory normal
• AST/ALT ≤5 X upper limit of laboratory normal
• Total bilirubin ≤1.5X upper limit of laboratory normal
• BNP ≤ 3 times the baseline value and upper limit of laboratory normal
• Troponin I ≤ upper limit of laboratory normal
• hsCRP ≤ upper limit of laboratory normal
• Cystatin ≤ upper limit of laboratory normal
• PT/INR ≤1.5X upper limit of laboratory normal

You may not qualify if:

• 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.
• Pregnant or lactating women, as treatment involves risks to the embryo or fetus.
• Other medical or psychiatric conditions that in the opinion of the Principal Investigator would preclude safe participation in protocol.
• 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

Sponsors & Collaborators

• Providence Health & Services: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Providence Cancer Center

Portland, Oregon, 97213, United States

Location

Related Publications (1)

• 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.

  PMID: 35952709 DERIVED

Related Links

• Providence Cancer Center Clinical Trials

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

LY-2157299; Capecitabine; Fluorouracil

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Kristina Young, MD, PhD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

• Todd Crocenzi, MD

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2016
• First Posted: February 23, 2016
• Study Start: March 24, 2016
• Primary Completion: January 26, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)