Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer

NCT02368886 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: RU021407INCI-2015-00011P30CA015083
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 22

Brief Summary

This randomized phase II trial studies how well lower-dose compared to standard dose regorafenib works in treating patients with colorectal cancer that has spread from the primary site (place where it started) to other places in the body and does not respond to treatment. Regorafenib may stop the growth of colorectal cancer by blocking the growth of new blood vessels necessary for tumor growth and by blocking some of the enzymes needed for cell growth. It is not yet known whether lower-dose or standard dose regorafenib is more effective in treating patients with colorectal cancer. Clobetasol propionate is a steroid cream that is commonly used to treat a variety of skin conditions and may help prevent hand-foot skin reactions in patients receiving regorafenib.

Conditions

Colon Adenocarcinoma; Rectal Adenocarcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients in Each Arm Who Complete 2 Cycles of Protocol Treatment and Initiate Cycle 3

  Fisher exact test will be used to detect a difference course 3 between arms (starting low dose \[pooled arm A1 and A2\] versus \[vs.\] standard dose \[pooled arm B1 and B2\]). The proportion of patients who complete 2 courses of protocol treatment and initiate course 3 will be computed by arm with its 95% confidence interval using exact method.

  At 8 weeks

Secondary Outcomes (8)

• Overall Survival (OS)

  Time from randomization to death due to any cause, assessed up to 2 years

• Progression Free Survival (PFS)

  Time from randomization to the earlier of disease progression or death due to any cause, where progressed disease (PD) is defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, assessed up to 2 years

• Time to Progression (TTP)

  Time from randomization to disease progression, where PD is defined by RECIST 1.1, assessed up to 2 years

• Cumulative (Total) Dose of Regorafenib Received by Patients in the First Two Cycles

  Up to 8 weeks

• Dose Intensity of Regorafenib Received by Patients in the First Two Cycles as Measured by the Percentage of Planned Dose Received

  Up to 8 weeks

Other Outcomes (1)

• Pharmacokinetics (PK) Parameters of Regorafenib Using Liquid Chromatography Mass Spectrometry

  Baseline, prior to treatment, days 7, 14, and 21 prior to treatment (course 1), and days 1 and 21 prior to treatment (course 2)

Study Arms (4)

Arm A1 (lower-dose regorafenib, pre-emptive clobetasol)

EXPERIMENTAL

Patients receive lower-dose regorafenib PO QD on days 1-21 and pre-emptive clobetasol propionate given topically BID for 12 weeks, beginning on day 1 of regorafenib.

Drug: Clobetasol Propionate; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Drug: Regorafenib

Arm A2 (lower-dose regorafenib, reactive clobetasol)

EXPERIMENTAL

Patients receive lower-dose regorafenib PO as in Arm A1 and reactive clobetasol propionate given topically BID beginning on day 1 per physician discretion upon occurrence of PPES grade \>= 1.

Drug: Clobetasol Propionate; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Drug: Regorafenib

Arm B1 (standard dose regorafenib, pre-emptive clobetasol)

EXPERIMENTAL

Patients receive standard dose regorafenib PO QD on days 1-21 and pre-emptive clobetasol propionate as in Arm A1.

Drug: Clobetasol Propionate; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Drug: Regorafenib

Arm B2 (standard dose regorafenib, reactive clobetasol)

EXPERIMENTAL

Patients receive standard dose regorafenib PO as in Arm B1 and reactive clobetasol propionate as in Arm A2.

Drug: Clobetasol Propionate; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Drug: Regorafenib

Interventions

Clobetasol Propionate DRUG

Given topically

Also known as: Olux-E

Arm A1 (lower-dose regorafenib, pre-emptive clobetasol); Arm A2 (lower-dose regorafenib, reactive clobetasol); Arm B1 (standard dose regorafenib, pre-emptive clobetasol); Arm B2 (standard dose regorafenib, reactive clobetasol)

Pharmacological Study OTHER

Correlative studies

Arm A1 (lower-dose regorafenib, pre-emptive clobetasol); Arm A2 (lower-dose regorafenib, reactive clobetasol); Arm B1 (standard dose regorafenib, pre-emptive clobetasol); Arm B2 (standard dose regorafenib, reactive clobetasol)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A1 (lower-dose regorafenib, pre-emptive clobetasol); Arm A2 (lower-dose regorafenib, reactive clobetasol); Arm B1 (standard dose regorafenib, pre-emptive clobetasol); Arm B2 (standard dose regorafenib, reactive clobetasol)

Regorafenib DRUG

Given PO

Also known as: BAY 73-4506, Stivarga

Arm A1 (lower-dose regorafenib, pre-emptive clobetasol); Arm A2 (lower-dose regorafenib, reactive clobetasol); Arm B1 (standard dose regorafenib, pre-emptive clobetasol); Arm B2 (standard dose regorafenib, reactive clobetasol)

Eligibility Criteria

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

You may qualify if:

• Histological or cytological documentation of adenocarcinoma of the colon or rectum
• Advanced or metastatic colorectal cancer with no curative options available and progression on previous standard therapy, including an EGFR inhibitor if KRAS wild-type
• Measurable or non-measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Life expectancy of \>= 3 months
• Absolute neutrophil count (ANC) \> 1500/mm\^3 (obtained =\< 7 days prior to randomization)
• Platelet count \> 100,000/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 investigator

You may not qualify if:

• Prior treatment with regorafenib
• Major surgical procedure, open biopsy, or significant traumatic injury =\< 28 days prior to randomization
• Congestive heart failure \> New York Heart Association (NYHA) class 2
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months) or myocardial infarction less than 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 4.0
• 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 grade 3 =\< 4 weeks prior to randomization
• Non-healing wound, ulcer, or bone fracture

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (22)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46628, United States

Location

Siouxland Regional Cancer Center

Sioux City, Iowa, 51101, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Hematology Oncology Associates of Central New York-East Syracuse

East Syracuse, New York, 13057, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Toledo Clinic Cancer Centers-Toledo

Toledo, Ohio, 43623, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Wellmont Medical Associates Oncology and Hematology-Kingsport

Kingsport, Tennessee, 37660, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Related Publications (2)

• Bekaii-Saab TS, Ou FS, Ahn DH, Boland PM, Ciombor KK, Heying EN, Dockter TJ, Jacobs NL, Pasche BC, Cleary JM, Meyers JP, Desnoyers RJ, McCune JS, Pedersen K, Barzi A, Chiorean EG, Sloan J, Lacouture ME, Lenz HJ, Grothey A. Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study. Lancet Oncol. 2019 Aug;20(8):1070-1082. doi: 10.1016/S1470-2045(19)30272-4. Epub 2019 Jun 28.

  PMID: 31262657 DERIVED

• Weinberg BA, Hartley ML, Salem ME. Precision Medicine in Metastatic Colorectal Cancer: Relevant Carcinogenic Pathways and Targets-PART 2: Approaches Beyond First-Line Therapy, and Novel Biologic Agents Under Investigation. Oncology (Williston Park). 2017 Jul 15;31(7):573-80.

  PMID: 28712102 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Colorectal Neoplasms

Interventions

Clobetasol; 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

Intervention Hierarchy (Ancestors)

Betamethasone; Steroids, Fluorinated; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Tanios Bekaii-Saab, M.D.
• Organization: Mayo Clinic Arizona

Bekaii-Saab.Tanios@mayo.edu

507/266-0800

Study Officials

• Tanios Bekaii-Saab

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2015
• First Posted: February 23, 2015
• Study Start: March 27, 2015
• Primary Completion: September 1, 2017
• Study Completion: March 2, 2023
• Last Updated: June 18, 2025
• Results First Posted: July 26, 2019

Record last verified: 2025-06

Locations

US (22)