Preoperative Immunotherapy (Pembrolizumab) for Patients With Colorectal Cancer and Resectable Hepatic Metastases

NCT03844750 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 187015NCI-2018-03165
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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). 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).

Conditions

Stage IV Colorectal Cancer AJCC v8; Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Metastatic Malignant Neoplasm in the Liver

Keywords

Resectable hepatic metastases; Surgery; Immunotherapy; Adjuvant Treatment

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years

Secondary Outcomes (7)

• Proportion of Participants With Treatment-related, Adverse Events

  Up to 2 years

• Proportion of Participants With Events of Clinical Interest (ECIs)

  Up to 2 years

• Proportion of Participants With Perioperative Complications

  Up to 1 month

• Proportion of Participants With an R0 Resection

  Up to 1 month

• Proportion of Participants With a Pathologic Response

  Up to 1 year

Study Arms (1)

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

Procedure: Hepatectomy; Biological: Pembrolizumab; Drug: Vactosertib

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (vactosertib, pembrolizumab, surgery)

Vactosertib DRUG

Given orally

Also known as: EW-7197

Treatment (vactosertib, pembrolizumab, surgery)

Hepatectomy PROCEDURE

Undergo liver resection.

Also known as: Liver Resection

Treatment (vactosertib, pembrolizumab, surgery)

Eligibility Criteria

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

You may qualify if:

• 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.
• a. FOLFOX or capecitabine combined with oxaliplatin (CapeOx) does not need to be a direct lead-in to this study.
• b. 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.
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• MedPacto, Inc.: collaborator
• Chloe Atreya, MD, PhD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Hepatectomy; pembrolizumab; vactosertib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Digestive System Surgical Procedures; Surgical Procedures, Operative

Limitations and Caveats

The study was terminated earlier than expected.

Results Point of Contact

• Title: Dr. Chloe Atreya, MD
• Organization: University of California, San Francisco

Chloe.Atreya@ucsf.edu

(415) 476-1000

Study Officials

• Chloe Atreya, MD, Ph.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: February 18, 2019
• Study Start: July 22, 2019
• Primary Completion: September 30, 2025
• Study Completion: September 30, 2025
• Last Updated: December 31, 2025
• Results First Posted: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

US (1)