Regorafenib, With Cetuximab or Panitumumab, for the Treatment of Unresectable, Locally Advanced, or Metastatic Colorectal Cancer

Running, not enrolling · Phase 2

Conditions studied: BRAF V600E Negative, KRAS Gene Mutation Negative, Locally Advanced Unresectable Colorectal Adenocarcinoma, Metastatic Colorectal Adenocarcinoma, NRAS Gene Mutation Negative, Stage III Colorectal Cancer AJCC v8, Stage IIIA Colorectal Cancer AJCC v8, Stage IIIB Colorectal Cancer AJCC v8, Stage IIIC Colorectal Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8, Stage IVA Colorectal Cancer AJCC v8, Stage IVB Colorectal Cancer AJCC v8, Stage IVC Colorectal Cancer AJCC v8

In brief

This phase II trial how well regorafenib and anti-EGFR therapy (cetuximab or panitumumab) works for the treatment of patients with colorectal cancer that cannot be removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic). Regorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab or panitumumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The purpose of this research study is to compare the effects, good and/or bad, of taking regorafenib follow by cetuximab or panitumumab, to those that receive cetuximab or panitumumab before regorafenib.

Key facts

Study ID

NCT04117945

Run by

Academic and Community Cancer Research United

People needed

22

Starts

2020-03-03

Expected to finish

2025-03-31

Last updated by the study team

2024-09-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically proven, unresectable distant metastatic or locally advanced colorectal adenocarcinoma
• KRAS, NRAS wild type
• BRAF v600E wildtype
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Life expectancy of >= 3 months per estimation of treating physician
• Absolute neutrophil count (ANC) >= 1200/mm\^3 (obtained =< 7 days prior to randomization)
• Platelet count >= 75,000/mm\^3 (obtained =< 7 days prior to randomization)
• Hemoglobin >= 9.0 g/dL (obtained =< 7 days prior to randomization)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 7 days prior to randomization)
• Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) (obtained =< 7 days prior to randomization)
• Serum creatinine =< 1.5 x ULN (obtained =< 7 days prior to randomization)
• International normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 x ULN (obtained =< 7 days prior to randomization)
• NOTE: Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care
• Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for patients with liver involvement of their cancer) (obtained =< 7 days prior to randomization)
• Negative serum pregnancy test done =< 7 days prior to randomization for women of childbearing potential only.
• NOTE: Post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test. The definition of adequate contraception will be based on the judgment of the treating physician
• Provide informed written consent
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Disease progression on or intolerable to any of the following: fluoropyrimidine, oxaliplatin and irinotecan
• Able to swallow and retain oral medication
• Willing to provide tissue and blood samples for correlative research purposes
• Willing to allow transfer of tissue and blood samples, clinical information, and outcome data collected from this trial for future research

You may not qualify if…

• Prior treatment with regorafenib, cetuximab or panitumumab
• Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days prior to randomization
• Congestive heart failure > New York Heart Association (NYHA) class 2.
• NOTE: Class 3 is defined as marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g., walking short distances (20-100m). They are comfortable at rest. Class 4 is defined as patients with severe limitations. Experiences symptoms even while at rest. Mostly bed bound
• Unstable angina (angina symptoms at rest), new-onset angina (begun =< 3 months prior to randomization) or myocardial infarction =< 6 months prior to randomization
• Cardiac arrhythmias requiring anti-arrhythmic therapy. Note: Pace makers, beta blockers or digoxin are permitted
• Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management)
• History of or current pheochromocytoma
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism =< 6 months prior to randomization
• Ongoing infection > grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0
• Known history of chronic hepatitis B or C
• Patients with seizure disorder requiring medication
• Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of randomization and is clinically stable with respect to the tumor at the time of randomization. Note: Patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
• History of organ allograft (including corneal transplant)
• Evidence or history of bleeding diathesis or any hemorrhage or bleeding event > CTCAE v5.0 grade 3 =< 4 weeks prior to randomization
• Non-healing wound, ulcer, or bone fracture
• Substance abuse, medical, psychological or social conditions that may interfere with the patient?s participation in the study or evaluation of the study results
• High-frequency microsatellite instability (MSI-H) patients who have not received prior PD-1 monoclonal antibody (mAb) therapy
• Concurrent anti-cancer therapy =< 3 weeks from randomization (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization)
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
• Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
• History of known persistent proteinuria of CTCAE v5.0 grade 3 or higher (>= 3.5 g/24 hrs)
• Any malabsorption condition
• Unresolved toxicity greater than CTCAE v5.0 grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity =< grade 2
• Albumin levels < 2.5 g/dl

Where it is running

• Mayo Clinic in Arizona — Scottsdale, Arizona, United States
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States
• MedStar Georgetown University Hospital — Washington D.C., District of Columbia, United States
• Mayo Clinic in Florida — Jacksonville, Florida, United States
• Emory University Hospital/Winship Cancer Institute — Atlanta, Georgia, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• University of Iowa/Holden Comprehensive Cancer Center — Iowa City, Iowa, United States
• Siouxland Regional Cancer Center — Sioux City, Iowa, United States
• Cancer Center of Kansas — Wichita, Kansas, United States
• Mayo Clinic — Rochester, Minnesota, United States
• University of Nebraska Medical Center — Omaha, Nebraska, United States
• Duke University Medical Center — Durham, North Carolina, United States
• Toledo Clinic Cancer Center — Toledo, Ohio, United States
• Allegheny General Hospital — Pittsburgh, Pennsylvania, United States
• Aurora Cancer Care-Milwaukee West — Wauwatosa, Wisconsin, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.