Rectal AdenocarcinomaPhase 2NCT02688712
ExIST Study of LY2157299 (Galunisertib) in Rectal Cancer
A Phase 2 study testing LY2157299, Capecitabine and Fluorouracil in people with Rectal Adenocarcinoma, run by Providence Health & Services at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Adenocarcinoma
- What is being tested?
- LY2157299, Capecitabine and Fluorouracil
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Mar 2016to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 18Show fewer
- 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
- Pre-menopausal women must have a negative pregnancy test on the day treatment starts and must avoid becoming pregnant while on treatment and for 3 months following completion of therapy. Men must avoid fathering a child while on treatment and for 3 months following completion of therapy. This exclusion is required due to the toxicities that chemotherapy, radiation, and LY2157299 may have on the forming fetus, spermatogenesis or the nursing child. Also, because pregnancy may alter immune function it may limit the treatment efficacy. Women of childbearing potential must agree to use a medically approved contraceptive method during the treatment period and for 3 months following the last dose of LY2157299. Contraceptive methods may include an intrauterine device [IUD], birth control pills or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection.
- 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.
Who cannot join
- 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)
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Read the 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:
- Determine the rate of pathologic complete response in patients with locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation and the investigational agent LY2157299
- Correlate immunoscore changes prior to therapy, during therapy, and at surgical resection with pathologic response and MRI parameters
- 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.
- Conditions
- Rectal Adenocarcinoma
- Being tested
- LY2157299, Capecitabine, Fluorouracil, Tumor specific mesorectal excision
- Keywords
- IIA, Xeloda, radiation therapy, LY2157299, tumor resection, capecitabine, 5FU, Fluorouracil, IIB, IIC, IV, neoadjuvant, Rectal cancer, Immunotherapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY2157299Drug
Also called Galunisertib
Small molecule inhibitor of transforming growth factor-beta signaling pathway
CapecitabineDrug
Also called Xeloda
Antimetabolite chemotherapy
FluorouracilDrug
Also called 5-fluorouracil , 5-FU, Adrucil, Efudex, Fluoroplex
Antimetabolite chemotherapy
Tumor specific mesorectal excisionProcedure or surgery
Tumor specific mesorectal excision
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: LY2157299; Drug: Capecitabine; Drug: Fluorouracil; Procedure: Tumor specific mesorectal excision |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of pathologic response
Complete response is defined as no viable tumor cells identified.
Measured: 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)
For the immunoscore, a value of 0 or 1 is assigned to each cell population of interest with 0 corresponding to a poor immune infiltrate and 1 corresponding to a favorable immune infiltrate as determined by immunohistochemistry.
Measured: Screening Visit, Day 15 Visit and Day of Surgery
MRI Parameters
Investigators will test a minimum of three MRI parameters including but not limited to ADC and f_p from the IVIM sequence, and Ktrans from the DCE sequence.
Measured: Screening Visit and Day 15 Visit
Immunologic monitoring parameters
The immunologic monitoring parameters will be combined to arrive at an aggregated measure of "pro-tumor immune environment" or "anti-tumor immune environment" using cell counts derived from flow cytometry of peripheral blood and serum measures of inflammation.
Measured: Days 1, 15, 22, 29, 43, 57 Visits, and Day of Surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2016 (estimated)
- Study start24 Mar 2016
- Primary completion26 Jan 2026
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Providence Health & Services
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Kristina Young, MD, PhD, Principal investigator, Providence Health & ServicesTodd Crocenzi, MD, Principal investigator, Providence Health & Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02688712
- Sponsor's protocol ID
- 15-050A
- Status last verified
- Apr 2026
- First submitted
- 25 Jan 2016
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
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.
PubMed 35952709
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of TGFβ Type I Receptor Inhibitor LY2157299 With Neoadjuvant Chemoradiation in Patients With Locally Advanced Rectal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT02688712
- Acronym / sponsor ID
- 15-050A
- Conditions
- Rectal Adenocarcinoma
- Keywords
- IIA, Xeloda, radiation therapy, LY2157299, tumor resection, capecitabine, 5FU, Fluorouracil
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Providence Health & ServicesUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- 24 Mar 2016 (actual)
- Primary completion
- 26 Jan 2026 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 23 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- Determine the rate of pathologic complete response in patients with locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation and the investigational agent LY2157299
- Correlate immunoscore changes prior to therapy, during therapy, and at surgical resection with pathologic response and MRI parameters
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LY2157299 + Chemoradiation + Surgery | Experimental | Drug: LY2157299, Drug: Capecitabine, Drug: Fluorouracil, Procedure: Tumor specific mesorectal excisionPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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:
- Pre-menopausal women must have a negative pregnancy test on the day treatment starts and must avoid becoming pregnant while on treatment and for 3 months following completion of therapy. Men must avoid fathering a child while on treatment and for 3 months following completion of therapy. This exclusion is required due to the toxicities that chemotherapy, radiation, and LY2157299 may have on the forming fetus, spermatogenesis or the nursing child. Also, because pregnancy may alter immune function it may limit the treatment efficacy. Women of childbearing potential must agree to use a medically approved contraceptive method during the treatment period and for 3 months following the last dose of LY2157299. Contraceptive methods may include an intrauterine device [IUD], birth control pills or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection.
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LY2157299Also: GalunisertibSmall molecule inhibitor of transforming growth factor-beta signaling pathway | Drug | LY2157299 + Chemoradiation + Surgery |
| CapecitabineAlso: XelodaAntimetabolite chemotherapy | Drug | LY2157299 + Chemoradiation + Surgery |
| FluorouracilAlso: 5-fluorouracil , 5-FU, Adrucil, Efudex, FluoroplexAntimetabolite chemotherapy | Drug | LY2157299 + Chemoradiation + Surgery |
| Tumor specific mesorectal excisionTumor specific mesorectal excision | Procedure or surgery | LY2157299 + Chemoradiation + Surgery |
Primary outcome
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.
3 secondary outcomes
Immunoscore (utilizing tumor tissue)
Time frame: Screening Visit, Day 15 Visit and Day of Surgery
MRI Parameters
Time frame: Screening Visit and Day 15 Visit
Immunologic monitoring parameters
Time frame: Days 1, 15, 22, 29, 43, 57 Visits, and Day of Surgery.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Derived from this study: PubMed 35952709Yamazaki 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.
- Providence Cancer Center Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Rectal Adenocarcinoma
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
RecruitingPhase 1
A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
Active, not recruitingPhase 2
Perioperative Cadonilimab (AK104) in Locally Advanced MSI-H/dMMR Gastric or Gastroesophageal Junction and Colorectal Adenocarcinoma
MSI-H/dMMR Gastric Carcinoma and Colorectal Cancer
Active, not recruitingPhase 1
P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects With Advanced or Metastatic Solid Tumors
Breast Cancer, Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristina Young, MD, PhD principal investigator
Providence Health & Services
Todd Crocenzi, MD principal investigator
Providence Health & Services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LY2157299, Capecitabine and Fluorouracil in people with Rectal Adenocarcinoma, run by Providence Health & Services at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02688712, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.