Regorafenib in Metastatic Colorectal Cancer

Sponsor
University of Rochester (Other)
Overall Status
Completed
CT.gov ID
NCT02466009
Collaborator
Bayer (Industry)
27
4
1
84.3
6.8
0.1

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

Study Type:
Interventional
Actual Enrollment :
27 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Regorafenib in Adults 70 Years or Older With Metastatic Colorectal Cancer: A Phase II Study
Actual Study Start Date :
Mar 1, 2015
Actual Primary Completion Date :
Jul 1, 2019
Actual Study Completion Date :
Mar 9, 2022

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:
  • Stivarga
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.]

    2. 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.]

    3. 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

    Ages Eligible for Study:
    70 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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.

    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.
    Responsible Party:
    Aram Hezel, Principal Investigator, University of Rochester
    ClinicalTrials.gov Identifier:
    NCT02466009
    Other Study ID Numbers:
    • 55555
    First Posted:
    Jun 9, 2015
    Last Update Posted:
    Aug 11, 2022
    Last Verified:
    Aug 1, 2022
    Keywords provided by Aram Hezel, Principal Investigator, University of Rochester
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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%
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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
    4. Secondary Outcome
    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

    [Not Specified]

    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
    Email Aram_Hezel@urmc.rochester.edu
    Responsible Party:
    Aram Hezel, Principal Investigator, University of Rochester
    ClinicalTrials.gov Identifier:
    NCT02466009
    Other Study ID Numbers:
    • 55555
    First Posted:
    Jun 9, 2015
    Last Update Posted:
    Aug 11, 2022
    Last Verified:
    Aug 1, 2022