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Colorectal CancerPhase 1/2NCT03657641

Regorafenib and Pembrolizumab in Treating Participants With Advanced or Metastatic Colorectal Cancer

A Phase 1/2 study testing Pembrolizumab and Regorafenib in people with Colorectal Cancer and Colorectal Cancer Metastatic, run by University of Southern California at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase I/II studies the side effects and best dose of regorafenib when given together with pembrolizumab in treating participants with colorectal cancer that has spread to other places in the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab and Regorafenib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
73 participants
Where
3 sitesUnited States
Study dates
21 Jun 2019to 31 Dec 2027
Phase
Phase 1/2
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

  • Patients who provided written informed consent to be subjects in this trial
  • Patients with histologically or cytologically confirmed advanced or metastatic colorectal cancer who had failed or are intolerant of oxaliplatin, irinotecan, and fluorouracil (5-FU)
  • Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • Patients capable of taking oral medication
  • Patients with evaluable or measurable lesions as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Neutrophil count >= 200/mm^3
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  • Platelet count >= 7.5 x 10^4/mm^3 (transfusion > 2 weeks before testing permitted)
  • Aspartate transaminase (AST), alanine transaminase (ALT) =< 2.5-times the upper limit of normal (=< 5-times in patients with liver metastasis)
  • Total bilirubin =< 1.5-times the upper limit of normal
  • Creatinine =< 1.5-times the upper limit of normal
  • Lipase =< 1.5 x the upper limit of normal (ULN)
  • International normalized ratio (INR) =< 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g. heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care
  • In women with the potential for pregnancy (including patients with amenorrhea due to medical reasons, such as chemical menopause), after consenting to the study, the patient must agree to take contraception for at least 23 weeks after taking the final dose of the investigational drug (a period of 30 days [ovulation cycle] is added to five times the elimination half-time of I/O agent). Women with the potential for pregnancy include those who have begun menstruation, who have not undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, and who have not gone through menopause. Menopause is defined as the consecutive absence of menstrual periods for >= 12 months
  • In the case of men, the patient must agree after consenting to the study to take contraception for at least 31 weeks after taking the final dose of the investigational drug (a period of 90 days [the spermatogenesis cycle] is added to five times the elimination half-time of immuno-oncology (I/O) agent

Who cannot join

  • Patients who have undergone systemic chemotherapy, radiotherapy, surgery, hormone therapy, or immunotherapy < 2 weeks before enrollment. Immune checkpoint blockade as pretreatment is permitted
  • Patients with a history of taking regorafenib
  • Patients with hypertension that is difficult to control (systolic blood pressure >= 150 mmHg and diastolic blood pressure >= 90 mmHg) despite treatment with several hypotensive agents
  • Patients with acute coronary syndrome (including myocardial infarction and unstable angina), and with a history of coronary angioplasty or stent placement performed within 6 months before enrollment
  • Patients with a large amount of pleural effusion or ascites requiring more than weekly drainage
  • Patients with a >= grade 3 active infection according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
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  • Patients with symptomatic brain metastasis
  • Patients with partial or complete gastrointestinal obstruction
  • Patients with interstitial lung disease with symptoms or signs of activity
  • Patients who test positive for either anti-human immunodeficiency virus (HIV)-1 antibodies, anti-HIV-2 antibodies, anti-human T-lymphotropic virus (HTLV)-1 antibodies, hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV) antibodies*
  • Patients who test positive for either anti-hepatitis B surface antigen (HBs) or anti-hepatitis B core antigen (HBc) antibodies, and those who have hepatitis B virus (HBV)-deoxyribonucleic acid (DNA) measurements greater than the detection sensitivity will also be excluded
  • Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease
  • Patients who require systemic corticosteroids (excluding temporary usage for tests, prophylactic administration for allergic reactions, or to alleviate swelling associated with radiotherapy) or immunosuppressants, or who have received such a therapy < 14 days before enrollment in the present study
  • Patients with a history or findings of >= grade III congestive heart failure according to the New York Heart Association functional classification
  • Patients with a seizure disorder who require pharmacotherapy
  • Persistent proteinuria > 3.5 g/24 hours measured by urine protein-creatinine ratio from a random urine sample (>= grade 3, NCI-CTCAE version [v] 4.0)
  • Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
  • Major surgical procedure or significant traumatic injury within 28 days before start of study medication
  • Non-healing wound, non-healing ulcer, or non-healing bone fracture
  • Patients with evidence or history of any bleeding diathesis, irrespective of severity
  • Any hemorrhage or bleeding event >= CTCAE grade 3 within 4 weeks prior to the start of study medication
  • Women who are pregnant or breastfeeding, or with the potential for pregnancy
  • EXCLUDED THERAPIES AND MEDICATIONS, PREVIOUS AND CONCOMITANT
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib and pembrolizumab)
  • Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 2 weeks of trial entry (signing of the informed consent form is OK in the washout period)
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
  • Therapeutic anticoagulation with vitamin-K antagonists (e.g., warfarin) or with heparins and heparinoids. However, prophylactic anticoagulation as described below is allowed:
  • Low dose warfarin (1 mg orally, once daily) with PT-INR =< 1.5 x ULN is permitted. Infrequent bleeding or elevations in PT-INR have been reported in some subjects taking warfarin while on regorafenib therapy. Therefore, subjects taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR or clinical bleeding episodes
  • Low dose aspirin (=< 100 mg daily)
  • Prophylactic doses of heparin
  • During the study, strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John?s wort) are not permitted
  • Live vaccines administered < 30 days before the initiation of treatment with the investigational drug and during the trial period. Examples of live vaccines are as follows (however, the list is not exhaustive): measles, mumps, rubella, chicken pox/herpes zoster, yellow fever, rabies, BCG for tuberculosis, and typhoid vaccines. Inoculation with inactive vaccines (e.g., seasonal influenza vaccines) is permitted; however, the intranasal administration of attenuated influenza vaccines (e.g., Flu-Mist) is prohibited
  • Systemic glucocorticoids for purposes other than treating symptoms caused by notable events with a suspected immunological etiology. Upon deliberation with the trial coordinating committee, the use of corticosteroids may be permitted according to the physiological dose required to alleviate symptoms (e.g., to control symptoms of acute asthma)

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • City of Hope

    Duarte, California, 91010

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase I/II Study of Regorafenib and Pembrolizumab in Metastatic Colorectal Cancer Patients in 3rd and 4th Line Setting

This phase I/II studies the side effects and best dose of regorafenib when given together with pembrolizumab in treating participants with colorectal cancer that has spread to other places in the body. Drugs used in chemotherapy, such as regorafenib, 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. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Giving regorafenib and pembrolizumab may work better at treating colorectal cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess safety of the combination and identification of the recommended dose (RD) for combination therapy. (Phase I) II. To evaluate preliminary efficacy and tolerability of the combination RD of regorafenib and pembrolizumab. (Phase II)

EXPLORATORY OBJECTIVES:

  1. The associations between biomarkers and clinical outcome will be investigated.

OUTLINE: This is a phase I, dose-escalation study of regorafenib followed by a phase II study.

Participants receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and regorafenib orally (PO) once daily (QD) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up periodically.

Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • PembrolizumabBiological

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

    Given IV

  • RegorafenibDrug

    Also called BAY 73-4506, Stivarga

    Given PO

Study groups in NCT03657641
Study groupRoleWhat they receive
Treatment (pembrolizumab, regorafenib)ExperimentalParticipants receive pembrolizumab IV over 30 minutes on day 1 and regorafenib PO QD on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Pembrolizumab; Drug: Regorafenib

What is being measured

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

  1. Number of Patients With Dose Modification Due to Toxicity

    Number of patients that required a dose modification while on study treatment, due to a Dose limiting toxicity (DLT), during Phase I and Phase II. DLT was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03 and is defined in the study protocol section 6.2.

    Measured: At the end of Course 1 (each course is 21 days)

  2. Progression-free Survival (PFS) (Phase II)

    PFS will be calculated from the start of treatment (day 1 of cycle 1) to the first observation of disease progression or death whichever comes first, or to the latest follow up. Kaplan Meier curves will be used for PFS plot. Medians of PFS and their 95% CI confidence intervals will be given.

    Measured: At first observation of disease progression or death whichever comes first, up to 3 years and 8 months.

  3. Overall Survival (OS)

    OS will be calculated from the start of treatment (day 1 or cycle 1) to death from any cause. Kaplan Meier curves will be used to OS plot. Medians and their 95%CI confidence intervals will be given.

    Measured: At last date known to be alive, up to 3 years and 8 months.

Timeline

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

  1. First posted5 Sep 2018
  2. Study start21 Jun 2019
  3. Primary completion27 Feb 2023
  4. Study completion31 Dec 2027 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
73 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03657641
Sponsor's protocol ID
3C-17-3
Other IDs
NCI-2018-01625, 3C-17-3, P30CA014089
Status last verified
Jun 2026
First submitted
30 Aug 2018
Last updated
16 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pembrolizumab and Regorafenib in people with Colorectal Cancer and Colorectal Cancer Metastatic, run by University of Southern California at 3 sites 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 14 inclusion and 33 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 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 16 Jun 2026). 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?

Number of Patients With Dose Modification Due to Toxicity (time frame: At the end of Course 1 (each course is 21 days)). The study lists 3 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 NCT03657641.

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 16 Jun 2026.

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