Metastatic Malignant Neoplasm in the LiverPhase 2NCT03844750
Preoperative Immunotherapy (Pembrolizumab) for Patients With Colorectal Cancer and Resectable Hepatic Metastases
A Phase 2 study testing Hepatectomy, Pembrolizumab and Vactosertib in people with Metastatic Malignant Neoplasm in the Liver and Stage IV Colorectal Cancer AJCC v8, run by Chloe Atreya, MD, PhD at 1 site in United States.
Trial summary
This phase II trials studies how well pembrolizumab and vactosertib work after standard of care chemotherapy in patients with colorectal cancer that has spread to the liver that can be removed by surgery (resectable hepatic metastases). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Malignant Neoplasm in the Liver, Stage IV Colorectal Cancer AJCC v8, Stage IVA Colorectal Cancer AJCC v8
- What is being tested?
- Hepatectomy, Pembrolizumab and Vactosertib
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jul 2019to 30 Sep 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Has histologically or cytologically confirmed CRC with liver metastases. In addition to liver metastases, extrahepatic metastases (e.g. pulmonary metastases) may be permitted if all other eligibility criteria are met. Participants are permitted to have primary tumor in situ (Neoadjuvant Arm only).
- Has received previous oxaliplatin-based chemotherapy.
- FOLFOX or capecitabine combined with oxaliplatin (CapeOx) does not need to be a direct lead-in to this study.
- If chemotherapy is a direct lead-in to this study, concurrent mAb therapy (bevacizumab, cetuximab, or panitumumab) is acceptable, however the antibody must be omitted from the final cycle of chemotherapy prior to pembrolizumab.
- Is an appropriate candidate to undergo liver biopsy and resection (+/-ablation) of liver metastases (Neoadjuvant Arm Only).
- Is willing and able to provide written informed consent/assent for the trial. The participants may also provide consent for Future Biomedical Research. However, may participate in the main trial without participating in Future Biomedical Research.
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- Is >=18 years of age on day of signing informed consent.
- Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions (Neoadjuvant Arm Only).
- Is willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained after last dose of standard of care lead-in chemotherapy [if applicable] and within 28 days prior to first dose of pembrolizumab (Neoadjuvant Arm Only).
- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- Has adequate organ function within 10 days of treatment initiation.
- Absolute neutrophil count (ANC) >= 1,500/microliter (uL) (within 10 days of treatment initiation).
- Platelets >= 100,000/uL (within 10 days of treatment initiation).
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment).
- Serum creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)) >= 60 mL/min for participants with creatinine levels > 1.5 x institutional ULN (within 10 days of treatment initiation).
- Creatinine clearance should be calculated per institutional standard.
- Serum total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 ULN (within 10 days of treatment initiation).
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =< 2.5 x ULN (within 10 days of treatment initiation).
- Albumin >= 2.5 mg/dL (within 10 days of treatment initiation).
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 10 days of treatment initiation).
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participants is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 10 days of treatment initiation).
- Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication (day 1). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
- Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participants.
- Have locally confirmed microsatellite stable (MSS) or Mismatch repair proficient (pMMR) Colorectal cancer (CRC). MSS is defined as 0-1 allelic shifts among 3-5 tumor microsatellite loci using a Polymerase chain reaction (PCR)-based assay. pMMR is defined as presence of protein expression of 4 DNA mismatch repair (MMR) enzymes (MLH1, MSH2, MSH6 and PMS2) by immunohistochemistry.
- Have no radiographic evidence of malignancy as assessed by Investigator (Adjuvant Phase Only).
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks since the last dose of the previous investigational agent or device use.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Has active hepatitis B (defined as hepatitis B surface antigen (HBsAg) reactive) or active hepatitis C virus (HCV) (defined as HCV RNA [qualitative] is detected) infection.
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- Has received prior anti-cancer monoclonal antibody (mAb), systemic anticancer therapy other than FOLFOX (including investigational agents), targeted small molecule therapy, or radiation therapy within 14 days prior to the first dose of study treatment (day 1).
- Note: Participants must have recovered from all adverse events (AEs) due to a previous therapies to =< grade 1 or baseline. Participant with grade 2 neuropathy or alopecia are eligible. If a participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
- Has received FOLFOX less than 7 days prior to the first dose of study treatment (day 1). Has not recovered (i.e., =< grade 1 or at baseline) from AEs due to FOLFOX chemotherapy.
- Note: Participants with =< grade 2 neuropathy or alopecia are exceptions to this criterion and may qualify for the study.
- Has not recovered adequately from toxicity or complications of a surgery or other procedure, per the assessment of the treating investigator.
- Has received liver-directed therapy such as radiotherapy or yttrium-90 in the past year involving the lesion to be biopsied. (Neoadjuvant Arm only)
- Has a known additional malignancy that is progressing or has required active treatment within 5 years prior.
- Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression by imaging for at least 4 weeks by repeat imaging [repeat imaging should be performed during the study screening]), clinically stable, and without requirement of steroid treatment for at least 14 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating investigator. Anticoagulation that cannot be safely held to perform the liver biopsy is an example of a contraindication to participation.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has received any prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137). (Neoadjuvant Arm Only).
- 17. Has severe hypersensitivity (>= grade 3) to pembrolizumab and/or to any of pembrolizumab's excipients.
- 18. Has received a live or live-attenuated vaccine within 30 days prior to first dose of the trial drug. Administration of killed vaccines are allowed.
- 19. Has inferior vena cava/cardiac involvement based on imaging. 20. Has had encephalopathy in the last 6 months. Those participants on rifaximin or lactulose to control their encephalopathy are not allowed.
- 21. Has had a solid organ or hematologic transplant. 22. Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thora- or paracentesis) is eligible.
- 23. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III/IV), uncontrolled hypertension (>=150/90mmHg), unstable angina pectoris or myocardial infarction (≤ 6 months prior to screening), uncontrolled cardiac arrhythmia, clinically significant cardiac valvulopathy requiting treatment, active interstitial lung disease, or serious chronic gastrointestinal conditions associated with diarrhea.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: A Phase II Study of Preoperative Immunotherapy in Patients With Colorectal Cancer and Resectable Hepatic Metastases
This phase II trials studies how well pembrolizumab and vactosertib work after standard of care chemotherapy in patients with colorectal cancer that has spread to the liver that can be removed by surgery (resectable hepatic metastases). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Vactosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and vactosertib after standard of care chemotherapy, but before liver metastases surgery, may help shrink the cancer prior to surgery. This study also investigates pembrolizumab and vactosertib after liver metastases surgery, decrease the risk of the cancer recurring (coming back).
Read the detailed description
PRIMARY OBJECTIVE:
- To characterize the change in the populations of tumor infiltrating lymphocytes (TILs) induced by neoadjuvant pembrolizumab plus vactosertib in participants with metastatic colorectal cancer (mCRC).
SECONDARY OBJECTIVES:
- To establish the safety/toxicity profile of pembrolizumab-based treatment in the perioperative setting for participants with colorectal cancer (CRC) with resectable hepatic metastases.
II. To explore the efficacy of pembrolizumab plus vactosertib in participants with CRC with resectable hepatic metastases.
EXPLORATORY OBJECTIVES:
- To determine the impact of pembrolizumab-based treatment on programmed death-ligand 1 (PD-L1) expression in tumor cells and tumor-infiltrating immune cells (TIICs), in participants with mCRC.
II. To determine the change in T cell repertoire within the tumor and blood induced by neoadjuvant pembrolizumab-based treatment in participants with mCRC.
III. To explore molecular profiles to identify potentially predictive biomarkers for participants with metastatic CRC treated with immunotherapy (including but not limited to microsatellite instability (MSI) testing).
IV. To correlate change in TIICs, PD-L1 expression, and T cell repertoires as well as molecular profiles with response/resistance and toxicity.
- To identify immune response messenger ribonucleic acid (mRNA) expression analysis to derive signatures associated with tumor response.
VI. To identify genomic mutations and gene copy aberrations associated with response and resistance to therapy.
VII. To correlate changes in microbiome composition and diversity with diet and lifestyle factors.
OUTLINE:
Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and vactosertib orally (PO) once a day (QD) for the first cycle 5 days a week for 2 weeks. Participants then undergo standard of care surgical removal of liver metastases approximately 2 weeks (minimum 1 week) after last dose of vactosertib.
OPTIONAL ADJUVANT TREATMENT: After surgery, eligible participants may also receive pembrolizumab and vactosertib every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants who do not undergo optional adjuvant treatment are followed up at 14 days and then every 90 days for up to 1 year. Participants who undergo optional adjuvant treatment are followed up at 30 days and then every 90 days for up to 2 years.
- Conditions
- Metastatic Malignant Neoplasm in the Liver, Stage IV Colorectal Cancer AJCC v8, Stage IVA Colorectal Cancer AJCC v8, Stage IVB Colorectal Cancer AJCC v8, Stage IVC Colorectal Cancer AJCC v8
- Being tested
- Hepatectomy, Pembrolizumab, Vactosertib
- Keywords
- Resectable hepatic metastases, Surgery, Immunotherapy, Adjuvant Treatment
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HepatectomyProcedure or surgery
Also called Liver Resection
Undergo liver resection.
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
VactosertibDrug
Also called EW-7197
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (vactosertib, pembrolizumab, surgery) | Experimental | Neoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles Receives: Procedure: Hepatectomy; Biological: Pembrolizumab; Drug: Vactosertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients With a >= 2-fold Increase in the Tumor-infiltrating Cells Per Unit Area (5 High Power Fields) in Post- Versus Pre Pembrolizumab Treatment Tumor Specimens.
Tumor-infiltrating immune cells (TIICs) will be analyzed by immunohistochemistry (IHC) in pre- and post-pembrolizumab treatment tumor specimens. The proportion of patients with a >= 2-fold increase (from pre- to post-treatment) in the number of TIICs per unit area (5 high power fields) will be calculated.
Measured: Up to 2 years
Secondary outcomes (7)
Proportion of Participants With Treatment-related, Adverse Events
Adverse events (AEs) will be analyzed including but not limited to all AEs, serious (S)AEs, and fatal AEs using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5 for classification. Due to the potential for late toxicities from pembrolizumab, patients will be followed for 1 year after their last dose of pembrolizumab.
Measured: Up to 2 years
Proportion of Participants With Events of Clinical Interest (ECIs)
Specific immune-related AEs (irAEs) will be collected and designated as immune-related events of clinical interest (ECIs). The study will use descriptive statistics to report on the safety/toxicity. Due to the potential for late toxicities from pembrolizumab, patients will be followed for 1 year after their last dose of pembrolizumab
Measured: Up to 2 years
Proportion of Participants With Perioperative Complications
The proportion of participants with reported perioperative complications related to study treatment will be reported.
Measured: Up to 1 month
Proportion of Participants With an R0 Resection
Participants who undergo surgical resection of liver metastases will be evaluable and the proportion of participants requiring an R0 resection will be reported
Measured: Up to 1 month
Proportion of Participants With a Pathologic Response
Participants who undergo surgical resection of liver metastases will be evaluable and the proportion of participants with a pathological tumor response will be reported
Measured: Up to 1 year
Objective Response Rate (ORR)
ORR is defined as the radiographic response as measured from baseline until the day of surgery will be evaluated using RECIST. Participants with a radiographic complete response (CR) or partial response (PR) before surgery will be reported.
Measured: Up to the time of surgery, approximately 14 days
Median Relapse-free Survival (RFS)
The time from objective response defined as radiographic evidence of relapse on surveillance CT scans after surgery to progression or death, whichever occurs first, will be used to determine relapse-free survival for participants who received adjuvant vactosertib and pembrolizumab.
Measured: Up to 2 years from 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 posted18 Feb 2019
- Study start22 Jul 2019
- Primary completion30 Sep 2025
- Study completion30 Sep 2025
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Malignant Neoplasm in the LiverStudies 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chloe Atreya, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, MedPacto, Inc.
- Responsible party
- Sponsor-investigator, Chloe Atreya, MD, PhD, University of California, San Francisco
- Investigators
- Chloe Atreya, MD, Ph.D., Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03844750
- Sponsor's protocol ID
- 187015
- Other IDs
- NCI-2018-03165
- Status last verified
- Dec 2025
- First submitted
- 7 Jan 2019
- Last updated
- 31 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data will be shared with study collaborators during the course of the study.
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Preoperative Immunotherapy in Patients With Colorectal Cancer and Resectable Hepatic Metastases
- ClinicalTrials.gov ID
- NCT03844750
- Acronym / sponsor ID
- 187015
- Conditions
- Metastatic Malignant Neoplasm in the Liver, Stage IV Colorectal Cancer AJCC v8, Stage IVA Colorectal Cancer AJCC v8, Stage IVB Colorectal Cancer AJCC v8, Stage IVC Colorectal Cancer AJCC v8
- Keywords
- Resectable hepatic metastases, Surgery, Immunotherapy, Adjuvant Treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Chloe Atreya, MD, PhDUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, MedPacto, Inc.
- Study start
- 22 Jul 2019 (actual)
- Primary completion
- 30 Sep 2025 (actual)
- Study completion
- 30 Sep 2025 (actual)
- First posted
- 18 Feb 2019 (actual)
- Results
- Posted 31 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trials studies how well pembrolizumab and vactosertib work after standard of care chemotherapy in patients with colorectal cancer that has spread to the liver that can be removed by surgery (resectable hepatic metastases). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Vactosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and vactosertib after standard of care chemotherapy, but before liver metastases surgery, may help shrink the cancer prior to surgery. This study also investigates pembrolizumab and vactosertib after liver metastases surgery, decrease the risk of the cancer recurring (coming back).
Detailed description
PRIMARY OBJECTIVE:
- To characterize the change in the populations of tumor infiltrating lymphocytes (TILs) induced by neoadjuvant pembrolizumab plus vactosertib in participants with metastatic colorectal cancer (mCRC).
SECONDARY OBJECTIVES:
- To establish the safety/toxicity profile of pembrolizumab-based treatment in the perioperative setting for participants with colorectal cancer (CRC) with resectable hepatic metastases.
II. To explore the efficacy of pembrolizumab plus vactosertib in participants with CRC with resectable hepatic metastases.
EXPLORATORY OBJECTIVES:
- To determine the impact of pembrolizumab-based treatment on programmed death-ligand 1 (PD-L1) expression in tumor cells and tumor-infiltrating immune cells (TIICs), in participants with mCRC.
II. To determine the change in T cell repertoire within the tumor and blood induced by neoadjuvant pembrolizumab-based treatment in participants with mCRC.
III. To explore molecular profiles to identify potentially predictive biomarkers for participants with metastatic CRC treated with immunotherapy (including but not limited to microsatellite instability (MSI) testing).
IV. To correlate change in TIICs, PD-L1 expression, and T cell repertoires as well as molecular profiles with response/resistance and toxicity.
- To identify immune response messenger ribonucleic acid (mRNA) expression analysis to derive signatures associated with tumor response.
VI. To identify genomic mutations and gene copy aberrations associated with response and resistance to therapy.
VII. To correlate changes in microbiome composition and diversity with diet and lifestyle factors.
OUTLINE:
Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and vactosertib orally (PO) once a day (QD) for the first cycle 5 days a week for 2 weeks. Participants then undergo standard of care surgical removal of liver metastases approximately 2 weeks (minimum 1 week) after last dose of vactosertib.
OPTIONAL ADJUVANT TREATMENT: After surgery, eligible participants may also receive pembrolizumab and vactosertib every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants who do not undergo optional adjuvant treatment are followed up at 14 days and then every 90 days for up to 1 year. Participants who undergo optional adjuvant treatment are followed up at 30 days and then every 90 days for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (vactosertib, pembrolizumab, surgery) | Experimental | Procedure: Hepatectomy, Biological: Pembrolizumab, Drug: VactosertibNeoadjuvant pembrolizumab will be administered at a fixed dose of 200 mg (IV) for 1 cycle plus 200 mg vactosertib (PO QD, 5 days per week x 2 weeks). Adjuvant pembrolizumab (400 mg IV) + vactosertib (200 mg PO QD Cycle 1, 5 days per week, Cycles 2 and beyond (200 mg BID, 5 days per week) will be administered for up to eight 6-week cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Has histologically or cytologically confirmed CRC with liver metastases. In addition to liver metastases, extrahepatic metastases (e.g. pulmonary metastases) may be permitted if all other eligibility criteria are met. Participants are permitted to have primary tumor in situ (Neoadjuvant Arm only).
- Has received previous oxaliplatin-based chemotherapy.
- Is an appropriate candidate to undergo liver biopsy and resection (+/-ablation) of liver metastases (Neoadjuvant Arm Only).
- Is willing and able to provide written informed consent/assent for the trial. The participants may also provide consent for Future Biomedical Research. However, may participate in the main trial without participating in Future Biomedical Research.
- Is >=18 years of age on day of signing informed consent.
Key exclusion criteria (25 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Has active hepatitis B (defined as hepatitis B surface antigen (HBsAg) reactive) or active hepatitis C virus (HCV) (defined as HCV RNA [qualitative] is detected) infection.
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 |
|---|---|---|
| HepatectomyAlso: Liver ResectionUndergo liver resection. | Procedure or surgery | Treatment (vactosertib, pembrolizumab, surgery) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Treatment (vactosertib, pembrolizumab, surgery) |
| VactosertibAlso: EW-7197Given orally | Drug | Treatment (vactosertib, pembrolizumab, surgery) |
Primary outcome
Proportion of Patients With a >= 2-fold Increase in the Tumor-infiltrating Cells Per Unit Area (5 High Power Fields) in Post- Versus Pre Pembrolizumab Treatment Tumor Specimens.
Time frame: Up to 2 years
Tumor-infiltrating immune cells (TIICs) will be analyzed by immunohistochemistry (IHC) in pre- and post-pembrolizumab treatment tumor specimens. The proportion of patients with a >= 2-fold increase (from pre- to post-treatment) in the number of TIICs per unit area (5 high power fields) will be calculated.
7 secondary outcomes
Proportion of Participants With Treatment-related, Adverse Events
Time frame: Up to 2 years
Proportion of Participants With Events of Clinical Interest (ECIs)
Time frame: Up to 2 years
Proportion of Participants With Perioperative Complications
Time frame: Up to 1 month
Proportion of Participants With an R0 Resection
Time frame: Up to 1 month
Proportion of Participants With a Pathologic Response
Time frame: Up to 1 year
Objective Response Rate (ORR)
Time frame: Up to the time of surgery, approximately 14 days
Median Relapse-free Survival (RFS)
Time frame: Up to 2 years from day of surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified data will be shared with study collaborators during the course of the study.
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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.
Chloe Atreya, MD, Ph.D. principal investigator
University of California, San Francisco
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 Hepatectomy, Pembrolizumab and Vactosertib in people with Metastatic Malignant Neoplasm in the Liver and Stage IV Colorectal Cancer AJCC v8, run by Chloe Atreya, MD, PhD 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 27 inclusion and 25 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: stopped early, as of the sponsor's last update on 31 Dec 2025. 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?
Yes. Results are posted in the registry (first posted 31 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Proportion of Patients With a >= 2-fold Increase in the Tumor-infiltrating Cells Per Unit Area (5 High Power Fields) in Post- Versus Pre Pembrolizumab Treatment Tumor Specimens. (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Dec 2025.