Metastatic Colorectal Cancer
Conditions
Keywords
Colorectal cancer, metastatic colorectal cancer, colorectal adenocarcinoma
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.
Interventions
DRUGRegorafenib
Regorafenib 120 mg (3 tablets) each day for 21 days of a 28 day cycle with the possibility of an increase in the dose to 160 mg (4 tablets).
Sponsors
Bayer
University of Rochester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects Who Experience Grade 3-5 Toxicity as a Measure of Safety and Tolerability. | From the date of study entry until 30 days after the last dose of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Responded to Study Treatment | 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. | Efficacy outcomes will be response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). A participant's best response will be classified per RECIST (Response evaluation criteria in solid tumors) criteria into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). If a participant's best response was complete response, partial response, or stable disease they were classified as responding to treatment. |
| Mean Difference in Quality of Life as Assessed by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Instrument | baseline and week 4 | The FACT-C instrument is an 11 question survey that asks general questions about the participants digestive system. The instrument scores range from 0-44 with higher scores indicating digestive problems. |
Other
| Measure | Time frame |
|---|---|
| Exploratory Outcome Measure: Percentage of Patients Who Had a Correlation Between Adverse Events and Response Rate | week 4 |
Countries
United States
Participant flow
Pre-assignment details
31 people were screened and 4 failed screening.
Participants by arm
| Arm | Count |
|---|---|
| Regorafenib 120 mg qd, 3 weeks on/1 week off (each cycle is 28 days)
Three 40 mg tablets should be taken in the morning with approximately 8 fluid ounces (240 mL) of water after a low-fat (\< 30% fat) breakfast.
Regorafenib: Regorafenib 120 mg (3 tablets) each day for 21 days of a 28 day cycle with the possibility of an increase in the dose to 160 mg (4 tablets). | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | Regorafenib |
|---|---|
| Age, Continuous | 74 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Number of concomitant medications | 13 number of concomitant medications |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 27 |
| other Total, other adverse events | 20 / 27 |
| serious Total, serious adverse events | 0 / 27 |
Outcome results
Primary
Number of Subjects Who Experience Grade 3-5 Toxicity as a Measure of Safety and Tolerability.
Time frame: From the date of study entry until 30 days after the last dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Regorafenib | Number of Subjects Who Experience Grade 3-5 Toxicity as a Measure of Safety and Tolerability. | 20 Participants |
Secondary
Mean Difference in Quality of Life as Assessed by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Instrument
The FACT-C instrument is an 11 question survey that asks general questions about the participants digestive system. The instrument scores range from 0-44 with higher scores indicating digestive problems.
Time frame: baseline and week 4
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Regorafenib | Mean Difference in Quality of Life as Assessed by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Instrument | -0.82 score on a scale |
Secondary
Percentage of Subjects Who Responded to Study Treatment
Efficacy outcomes will be response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). A participant's best response will be classified per RECIST (Response evaluation criteria in solid tumors) criteria into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). If a participant's best response was complete response, partial response, or stable disease they were classified as responding to treatment.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Regorafenib | Percentage of Subjects Who Responded to Study Treatment | 3.7 percentage of participants |
Other Pre-specified
Exploratory Outcome Measure: Percentage of Patients Who Had a Correlation Between Adverse Events and Response Rate
Time frame: week 4