AzTrials
AzTrials

Microsatellite StablePhase 2NCT03396926

Pembrolizumab, Capecitabine, and Bevacizumab for Treating Colorectal Cancer

A Phase 2 study testing Bevacizumab, Capecitabine and Specimen collection in people with Microsatellite Stable and Mismatch Repair Protein Proficient, run by University of California, San Francisco at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies the side effects and best dose of capecitabine when given together with pembrolizumab and bevacizumab, and investigates how well they work in treating patients with microsatellite stable colorectal cancer that has spread to nearby tissues or lymph nodes, has spread to other places in the… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bevacizumab, Capecitabine and Specimen collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 siteUnited States
Study dates
18 Apr 2018to 30 Jan 2024
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

  • Have histologically confirmed, locally advanced unresectable or metastatic (stage IV) colorectal adenocarcinoma
  • Have locally confirmed MSS or pMMR CRC; MSS is defined as 0-1 allelic shifts among 3-5 tumor microsatellite loci using a PCR-based assay; pMMR is defined as presence of protein expression of 4 MMR enzymes (DNA mismatch repair protein Mlh1 (MLH1), DNA mismatch repair protein Msh2 (MSH2), mutS homolog 6 (MSH6) and Mismatch repair endonuclease postmeiotic segregation increased 2 (PMS2) by immunohistochemistry.
  • Have stable disease or progression on a prior regimen containing infusional 5-FU or capecitabine according to the interpretation of the treating provider
  • Be willing and able to provide written informed consent/assent for the trial
  • Be 18 years of age on day of signing informed consent
  • Have measurable disease based on RECIST 1.1
Show all 22Show fewer
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion (phase II dose expansion cohort only); newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Demonstrate adequate organ function performed within 10 days of treatment initiation as defined below:
  • Absolute neutrophil count (ANC) >= 1,500 /mcL
  • Platelets >= 100,000 / microliter (mcL)
  • 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 >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN. Glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl)). Creatinine clearance should be calculated per institutional standard
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN. Patients with Gilbert's disease may be included if their direct bilirubin is ≤ 1.5 X ULN.
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT)) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
  • Albumin >= 2.5 mg/dL
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy; as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects 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 subjects 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 subject

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
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has a known history of active tuberculosis (TB) (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Hypersensitivity/intolerance to capecitabine, Infusional 5-Fluorouracil (5-FU), or bevacizumab
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
Show all 34Show fewer
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
  • Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Has active autoimmune disease that has required systemic treatment in the 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, etc.) is not considered a form of systemic treatment
  • Has known history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.
  • Has an active infection at the time of cycle 1 day 1 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 the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen (HBsAg) reactive) or hepatitis C (e.g., hepatitis C virus (HCV) ribonucleic acid [RNA] [qualitative] is detected)
  • Requires therapeutic anticoagulation with warfarin at baseline. Patients must be off warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to starting study drug, however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed
  • Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug
  • Known bleeding risk including serious hemorrhage or hemoptysis within the last 3 months; major surgery within the past 8 weeks or minor surgery within the past 4 weeks
  • Has known gastrointestinal bleeding or any other hemorrhage/bleeding event Common Terminology Criteria for Adverse Events (CTCAE) grade > 3 within 6 months of start of study drug
  • Has greater than 1+ proteinuria on a urine dipstick or equivalent routine laboratory analysis will require further testing with a urine protein to creatinine ratio (UPCR); UPCR must be calculated as follows: UPCR = protein concentration (mg/dL)/creatinine (mg/dL); if the UPCR >= 1, then the patient will not be eligible for study entry; however, if urinalysis or equivalent routine laboratory analysis shows no protein, then UPCR testing is not required
  • Has a history of non-healing wounds or ulcers, or bone re-fractures within 3 months of fracture
  • Has a history of arterial thromboembolism within 12 months of start of study drug
  • Has inadequately controlled hypertension (defined as systolic blood pressure greater than 150 mm Hg or diastolic blood pressure greater than 95 mm Hg). The use of anti-hypertensive medications to control blood pressure is permitted. Retesting is permitted.
  • Has a history of hypertensive crisis or hypertensive encephalopathy within 6 months prior to planned start of study drug
  • Has had clinically significant cardiovascular disease within 12 months of planned start of study drug, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
  • Has a known history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to planned start of study drug
  • Known reversible posterior leukoencephalopathy syndrome (RPLS)
  • Difficulty swallowing, malabsorption, active partial or complete bowel obstruction, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of capecitabine
  • Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: Phase II Study of Pembrolizumab Plus Capecitabine and Bevacizumab in Microsatellite Stable Metastatic Colorectal Cancer

This phase II trial studies the side effects and best dose of capecitabine when given together with pembrolizumab and bevacizumab, and investigates how well they work in treating patients with microsatellite stable colorectal cancer that has spread to nearby tissues or lymph nodes, has spread to other places in the body, or that cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab and bevacizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving capecitabine together with pembrolizumab and bevacizumab may work better in treating patients with colorectal cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the recommended phase 2 dose (RP2D)/maximum tolerated dose (MTD) of capecitabine when administered with pembrolizumab and bevacizumab. (Safety Lead-In Cohort) II. To evaluate the overall response rate (ORR) to pembrolizumab plus capecitabine and bevacizumab (complete or partial response rate per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) in subjects with metastatic or locally advanced unresectable microsatellite stable (MSS)/mismatch repair proficient (pMMR) colorectal carcinoma (CRC) that is stable or progressing on fluorouracil (5FU)-based therapy. (Phase II Expansion Cohort)

SECONDARY OBJECTIVES (Phase II Expansion Cohort):

  1. To determine the safety and tolerability of pembrolizumab in combination with capecitabine and bevacizumab.

II. To evaluate ORR per immune-related RECIST (irRECIST). III. To evaluate duration of response (DOR), disease control rate (DCR) and progression-free survival (PFS) per RECIST 1.1 and irRECIST and overall survival (OS).

EXPLORATORY OBJECTIVES:

  1. Correlation of outcomes to line of therapy; stable disease or progression on a prior regimen containing infusional 5-FU or capecitabine; prior exposure to bevacizumab; and primary tumor location.

II. To explore baseline immune profiles via PD-L1, and multiplex Immunohistochemistry (IHC) for identification of potentially predictive biomarkers in patients with metastatic or locally advanced, unresectable CRC treated with pembrolizumab-based combination therapy.

III. To characterize the change in the populations of tumor-infiltrating immune cells (TIICs) by IHC induced by pembrolizumab-based combination therapy in paired pre- and on-treatment tumor biopsies from patients with metastatic or locally advanced, unresectable MSS / pMMR CRC.

IV. To determine the change in T cell repertoire via next generation sequencing (NGS) within blood and tumor biopsy samples induced by pembrolizumab-based combination therapy in patients with metastatic or locally advanced, unresectable MSS/pMMR CRC.

  1. To establish human immune system (HIS) patient-derived xenograft (PDX) models from pre-treatment biopsies to a) analyze change in immune cell profiles HIS PDX models using the same techniques as described for corresponding patients, above and b) correlate response to pembrolizumab-containing therapy in patients and HIS PDX.

OUTLINE:

An initial safety lead-in will be performed to define the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D). Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1, bevacizumab IV over 30-90 minutes on day 1, and capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 3 weeks for up to 35 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 9 weeks until disease progression, start of new anti-cancer therapy, death, or end of the study whichever comes first

Being tested
Bevacizumab, Capecitabine, Specimen collection, Pembrolizumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given intravenously (IV)

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Given orally (PO)

  • Specimen collectionProcedure or surgery

    For use in correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT03396926
Study groupRoleWhat they receive
Safety Lead in Cohort: Treatment (pembrolizumab, bevacizumab, capecitabine)ExperimentalParticipants receive pembrolizumab IV over 30 minutes on day 1, bevacizumab IV over 30-90 minutes on day 1, and capecitabine PO BID on days 1-14. Treatment repeats every 3 weeks for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Bevacizumab; Drug: Capecitabine; Procedure: Specimen collection; Biological: Pembrolizumab
Expansion Cohort: Treatment (pembrolizumab, bevacizumab, capecitabine)ExperimentalParticipants receive pembrolizumab IV over 30 minutes on day 1, bevacizumab IV over 30-90 minutes on day 1, and capecitabine PO BID on days 1-14. Treatment repeats every 3 weeks for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Bevacizumab; Drug: Capecitabine; Procedure: Specimen collection; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Participants With Treatment-related, Dose-limiting Toxicities (DLT) (Safety Lead-In Cohort)

    A DLT evaluation of the first 6 participants will be conducted to confirm the safety of administering pembrolizumab at 200 mg (flat dosing) every three weeks with capecitabine and bevacizumab and include all participants in the safety lead in cohort who received at least 1 dose of study treatment. At least one laboratory or vital sign measurement obtained subsequent to at least one dose of study treatment is required for inclusion in the analysis including a baseline measure. Dose-limiting toxicity (DLT) must be clinically-significant toxicities which are at least possibly treatment-related per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4

    Measured: Up to 1 cycle (each cycle is 21 days)

  2. Overall Response Rate (ORR)

    ORR is defined as the percentage of the participants in the ASaT population who have a confirmed complete response (CR) or a partial response (PR) (Overall Response (OR) = CR + PR) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 on Computerized Tomography (CT) or magnetic resonance imaging or (MRI) imaging if a CT cannot be obtained. The ORR and 95% confidence interval will be provided using exact binomial method proposed by Clopper and Pearson (1934).

    Measured: Up to 4 years

Secondary outcomes (4)

  1. Disease Control Rate (DCR)

    DCR is defined as the percentage of participants who have achieved confirmed CR or PR or have demonstrated stable disease (SD) for at least 24 weeks prior to any evidence of progression assessed by RECIST and immune-related RECIST (irRECIST). The percentage of participants and 95% confidence interval, will be provided using exact binomial method proposed by Clopper and Pearson (1934).

    Measured: Up to 4 years

  2. Median Duration of Response (DOR)

    Duration of response is defined as the time from first documented evidence of CR or PR assessed by RECIST and irRECIST until disease progression or death due to any cause, whichever occurs first. Kaplan-Meier (KM) curves and median estimates from will be reported

    Measured: Up to 4 years

  3. Median Overall Survival (OS)

    OS is defined as the time from first day of study treatment to death due to any cause. Subjects without documented death at the time of the final analysis will be censored at the date of the last follow-up. KM curves and median estimates from the KM curves will be provided as appropriate.

    Measured: Up to 4 years

  4. Median Progression-Free Survival (PFS)

    PFS is defined as the time from first day of study treatment to the first documented disease progression or death due to any cause, whichever occurs first. Median estimates in months and the 95% confidence interval will be reported.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jan 2018
  2. Study start18 Apr 2018
  3. Primary completion30 Jan 2024
  4. Study completion30 Jan 2024

Resources

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03396926
Sponsor's protocol ID
174517
Other IDs
NCI-2017-02324
Status last verified
Feb 2025
First submitted
5 Jan 2018
Last updated
28 Feb 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bocobo A, Whitman J, Keenan BP, Koser KL, Kidder WA, Piawah S, Van Loon K, Behr SC, Kolli KP, Chen X, Onodera C, Pande M, Pollak M, Wang R, Babdor J, Spitzer MH, Zhang L, Fong L, Atreya CE. Phase II Study of Pembrolizumab Plus Capecitabine and Bevacizumab for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2026 Jun;25(2):271-282. doi: 10.1016/j.clcc.2026.02.003. Epub 2026 Feb 18.

    PubMed 41826077

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Capecitabine and Specimen collection in people with Microsatellite Stable and Mismatch Repair Protein Proficient, run by University of California, San Francisco 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 22 inclusion and 34 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: finished, as of the sponsor's last update on 28 Feb 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 28 Feb 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 Participants With Treatment-related, Dose-limiting Toxicities (DLT) (Safety Lead-In Cohort) (time frame: Up to 1 cycle (each cycle is 21 days)). The study lists 2 primary outcomes in all. 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 NCT03396926, 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 28 Feb 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in