Regorafenib in Metastatic Colorectal Cancer
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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. |
Drug: 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).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Number of Subjects Who Respond 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.]
- Association of Adverse Events With the Comprehensive Geriatric Assessments. [From the date of study entry until 30 days after the last dose of study treatment.]
- Subject's Quality of Life as Assessed by the Comprehensive Geriatric Assessment Form While Receiving Study Treatment. [From the date of study entry until 30 days after the last dose of study treatment.]
Eligibility Criteria
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:
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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
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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
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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.
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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
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Active or clinically significant cardiac disease.
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Evidence or history of bleeding diathesis or coagulopathy
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Any hemorrhage or bleeding event ≥ grade 3 within 4 weeks.
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Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident, deep vein thrombosis or pulmonary embolus within 6 months of informed consent
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History of other active malignancy within past 2 years.
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Patients with phaeochromocytoma
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Known history of human immunodeficiency virus infection or current chronic/active hepatitis B or C infection.
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Ongoing infection > grade 2
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Symptomatic metastatic brain or meningeal tumors
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Presence of non-healing wound, non-healing ulcer, or bone fracture
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Renal failure requiring hemo- or peritoneal dialysis
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Dehydration ≥ grade 1
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Patients with seizure disorder requiring medication
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Persistent proteinuria ≥ grade 3 Interstitial lung disease with ongoing signs and symptoms at the time of informed consent
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Pleural effusion or ascites that causes respiratory compromise, grade 2 dyspnea
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History of organ allograft including corneal transplant
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Known or suspected allergy or hypersensitivity to the study drug
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Any malabsorption condition
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Any condition which makes the subject unsuitable for trial participation
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Substance abuse, medical, psychological, or social conditions that may interfere with the subject's participation in the study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Mayo Clinic | Rochester | Minnesota | United States | 55901 |
2 | University of Rochester | Rochester | New York | United States | 14642 |
3 | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | 27514 |
4 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
Sponsors and Collaborators
- University of Rochester
- Bayer
Investigators
- Principal Investigator: Aram Hezel, M.D., University of Rochester
Study Documents (Full-Text)
More Information
Publications
None provided.- 55555
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 31 people were screened and 4 failed screening. |
Arm/Group Title | Regorafenib |
---|---|
Arm/Group Description | 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). |
Period Title: Overall Study | |
STARTED | 27 |
COMPLETED | 27 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Regorafenib |
---|---|
Arm/Group Description | 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). |
Overall Participants | 27 |
Age (years) [Median (Full Range) ] | |
Median (Full Range) [years] |
74
|
Sex: Female, Male (Count of Participants) | |
Female |
10
37%
|
Male |
17
63%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
1
3.7%
|
Not Hispanic or Latino |
26
96.3%
|
Unknown or Not Reported |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
0
0%
|
Native Hawaiian or Other Pacific Islander |
1
3.7%
|
Black or African American |
6
22.2%
|
White |
20
74.1%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (participants) [Number] | |
United States |
27
100%
|
Number of concomitant medications (number of concomitant medications) [Median (Full Range) ] | |
Median (Full Range) [number of concomitant medications] |
13
|
Outcome Measures
Title | Number of Subjects Who Experience Grade 3-5 Toxicity as a Measure of Safety and Tolerability. |
---|---|
Description | |
Time Frame | From the date of study entry until 30 days after the last dose of study treatment. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Regorafenib |
---|---|
Arm/Group Description | 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). |
Measure Participants | 27 |
Count of Participants [Participants] |
20
74.1%
|
Title | Number of Subjects Who Respond to Study Treatment. |
---|---|
Description | |
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. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Association of Adverse Events With the Comprehensive Geriatric Assessments. |
---|---|
Description | |
Time Frame | From the date of study entry until 30 days after the last dose of study treatment. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Subject's Quality of Life as Assessed by the Comprehensive Geriatric Assessment Form While Receiving Study Treatment. |
---|---|
Description | |
Time Frame | From the date of study entry until 30 days after the last dose of study treatment. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Adverse Events
Time Frame | 2 years | |
---|---|---|
Adverse Event Reporting Description | Grade 3-5 non-serious adverse events were reported. | |
Arm/Group Title | Regorafenib | |
Arm/Group Description | 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). | |
All Cause Mortality |
||
Regorafenib | ||
Affected / at Risk (%) | # Events | |
Total | 2/27 (7.4%) | |
Serious Adverse Events |
||
Regorafenib | ||
Affected / at Risk (%) | # Events | |
Total | 0/27 (0%) | |
Other (Not Including Serious) Adverse Events |
||
Regorafenib | ||
Affected / at Risk (%) | # Events | |
Total | 20/27 (74.1%) | |
Blood and lymphatic system disorders | ||
Anemia | 3/27 (11.1%) | |
Cardiac disorders | ||
Sinus bradycardia | 1/27 (3.7%) | |
Gastrointestinal disorders | ||
Abdominal pain | 1/27 (3.7%) | |
Gastrointestinal disorders - Other | 1/27 (3.7%) | |
Nausea | 1/27 (3.7%) | |
Rectal hemorrhage | 1/27 (3.7%) | |
Vomiting | 1/27 (3.7%) | |
General disorders | ||
Edema limbs | 1/27 (3.7%) | |
Fatigue | 10/27 (37%) | |
Injury, poisoning and procedural complications | ||
Intestinal stoma site bleeding | 1/27 (3.7%) | |
Investigations | ||
Alanine aminotransferase increased | 1/27 (3.7%) | |
Aspartate aminotransferase increased | 1/27 (3.7%) | |
Blood bilirubin increased | 1/27 (3.7%) | |
Investigations - Other | 1/27 (3.7%) | |
Metabolism and nutrition disorders | ||
Anorexia | 1/27 (3.7%) | |
Dehydration | 2/27 (7.4%) | |
Hypocalcemia | 1/27 (3.7%) | |
Hyponatremia | 5/27 (18.5%) | |
Hypophosphatemia | 2/27 (7.4%) | |
Musculoskeletal and connective tissue disorders | ||
Generalized muscle weakness | 1/27 (3.7%) | |
Muscle weakness lower limb | 1/27 (3.7%) | |
Pain in extremity | 1/27 (3.7%) | |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other | 2/27 (7.4%) | |
Nervous system disorders | ||
Dizziness | 1/27 (3.7%) | |
Presyncope | 1/27 (3.7%) | |
Syncope | 1/27 (3.7%) | |
Psychiatric disorders | ||
Confusion | 1/27 (3.7%) | |
Renal and urinary disorders | ||
Acute kidney injury | 1/27 (3.7%) | |
Respiratory, thoracic and mediastinal disorders | ||
Respiratory, thoracic and mediastinal disorders - Other | 1/27 (3.7%) | |
Skin and subcutaneous tissue disorders | ||
Palmar-plantar erythrodysesthesia syndrome | 4/27 (14.8%) | |
Vascular disorders | ||
hypertension | 16/27 (59.3%) | |
Thromboembolic event | 1/27 (3.7%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Aram Hezel |
---|---|
Organization | University of Rochester |
Phone | 585-275-5823 |
Aram_Hezel@urmc.rochester.edu |
- 55555