Clinical trial NCT02466009: Regorafenib in Metastatic Colorectal Cancer
Official title: Regorafenib in Adults 70 Years or Older With Metastatic Colorectal Cancer: A Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Colorectal cancer
metastatic colorectal cancer
colorectal adenocarcinoma
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2015-06-09
Enrollment: 27
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to measure high grade (3-5) toxicity of regorafenib and to monitor the impact of treatment with regorafenib on the quality of life in older adults with metastatic colorectal cancer.

Detailed description: Subjects will be asked to participate in the study because they are aged 70 or older and require treatment for colorectal cancer that has spread to other parts of the body and has not gotten better with other treatment. Subjects will undergo some initial tests to ensure that they meet all criteria necessary to participate in the study. Once the subject has completed initial testing and meets eligibility criteria, the subject will begin treatment with 120 mg of regorafenib (3 tablets) each day for 21 days (3 weeks) in a 28 day cycle (4 weeks). After the first cycle, the doctor will discuss the possibility of increasing the dose to 160 mg (4 tablets) each day for 21 days (3 weeks) in a 28 day cycle (4 weeks) based on the subjects health status. During the study, assessments will be performed to monitor the subjects tolerance and response to the treatment. Regorafenib will continue as long as the subject is tolerating the treatment and the subjects colorectal cancer is either responding to treatment or remains stable.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed colorectal adenocarcinoma
* Measurable metastatic disease.
* Age +/\> 70
* Progression on standard therapy, not a candidate for further chemotherapy or patient declines other options
* Life expectancy \>/= 12 weeks
* Able to understand and willing to sign written informed consent.
* Laboratory requirements:
* Total bili ≤ 1.5 x upper limit or normal
* Alanine aminotransferase \& Asparate aminotransferase ≤ 2.5 x upper limit or normal
* Serum creatinine ≤ 1.5 x upper limit or normal
* International normalized ratio/prothrombin time ≤ 1.5 x upper limit or normal
* Platelet count ≥ 100,000, hemoglobin ≥ 9 g/dL
* Absolute neutrophil count ≥ 1,500. Blood transfusion to meet the inclusion criteria not be allowed.
* Glomerular filtration rate ≥ 60 ml/min
* Subjects of childbearing potential must agree to use adequate contraception beginning at the signing informed consent form until at least 3 months after the last dose of study drug.
* Must be able to swallow and retain oral medications

Exclusion Criteria:

* Currently receiving other systemic therapy for metastatic colorectal cancer
* Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
* Uncontrolled hypertension despite optimal medical management
* Active or clinically significant cardiac disease.
* Evidence or history of bleeding diathesis or coagulopathy
* Any hemorrhage or bleeding event ≥ grade 3 within 4 weeks.
* Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident, deep vein thrombosis or pulmonary embolus within 6 months of informed consent
* History of other active malignancy within past 2 years.
* Patients with phaeochromocytoma
* Known history of human immunodeficiency virus infection or current chronic/active hepatitis B or C infection.
* Ongoing infection \> grade 2
* Symptomatic metastatic brain or meningeal tumors
* Presence of non-healing wound, non-healing ulcer, or bone fracture
* Renal failure requiring hemo- or peritoneal dialysis
* Dehydration ≥ grade 1
* Patients with seizure disorder requiring medication
* Persistent proteinuria ≥ grade 3 Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
* Pleural effusion or ascites that causes respiratory compromise, grade 2 dyspnea
* History of organ allograft including corneal transplant
* Known or suspected allergy or hypersensitivity to the study drug
* Any malabsorption condition
* Any condition which makes the subject unsuitable for trial participation
* Substance abuse, medical, psychological, or social conditions that may interfere with the subject's participation in the study.

Primary outcomes:
measure: Number of Subjects Who Experience Grade 3-5 Toxicity as a Measure of Safety and Tolerability.
timeFrame: From the date of study entry until 30 days after the last dose of study treatment.
Secondary outcomes:
measure: Percentage of Subjects Who Responded to Study Treatment
timeFrame: From the date of completion of three cycles of treatment until the date of progression of disease as determined by restaging scans up to 2 years.
measure: Mean Difference in Quality of Life as Assessed by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Instrument
timeFrame: baseline and week 4
Other outcomes:
measure: Exploratory Outcome Measure: Percentage of Patients Who Had a Correlation Between Adverse Events and Response Rate
timeFrame: week 4
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: University of Rochester
name: Aram Hezel, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.