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

NCT03657641 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 3C-17-3NCI-2018-01625P30CA014089
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Colorectal Cancer; Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLTs) (Phase I)

  Will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03. All DLTs will be listed by dose level.

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

• 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 and probabilities of PFS at 3 and 6 months and their 95% CI confidence intervals will be given.

  Up to 30 months after study entry

• 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 probabilities at 3 and 6 months and their 95%CI confidence intervals will be given.

  Up to 30 months after study entry

Study Arms (1)

Treatment (pembrolizumab, regorafenib)

EXPERIMENTAL

Participants 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.

Biological: Pembrolizumab; Drug: Regorafenib

Interventions

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (pembrolizumab, regorafenib)

Regorafenib DRUG

Given PO

Also known as: BAY 73-4506, Stivarga

Treatment (pembrolizumab, regorafenib)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

pembrolizumab; regorafenib

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

Study Officials

• Heinz-Josef Lenz, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: September 5, 2018
• Study Start: June 21, 2019
• Primary Completion: February 27, 2023
• Study Completion (Estimated): June 21, 2026
• Last Updated: July 4, 2025

Record last verified: 2025-07

Locations

US (3)