Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Oral Steroids for Regorafenib-induced Fatigue/Malaise in Unresectable mCRC (KSCC1402/HGCSG1402)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02288078
Recruitment Status : Unknown
Verified November 2014 by Hideo Baba, Kumamoto University.
Recruitment status was:  Recruiting
First Posted : November 11, 2014
Last Update Posted : November 13, 2014
Sponsor:
Information provided by (Responsible Party):
Hideo Baba, Kumamoto University

Brief Summary:
The objective of this randomized placebo-controlled Phase 2 study is to evaluate prophylactic effects of dexamethasone for fatigue and malaise (weakness, lethargy, malaise) resulting from regorafenib treatment, as well as to assess treatment continuation of regorafenib.

Condition or disease Intervention/treatment Phase
Rectal Cancer Other: General condition Other: Blood pressure Other: Patient Reported Outcome Other: Clinical findings Other: Hematology/blood chemistry Other: Coagulation and fibrinolysis system Other: Urinalysis Other: Medication check Other: Adverse event Other: Thyroid function test Other: Contrast-enhanced torso CT Other: Brain MRI Drug: Dexamethasone Drug: Regorafenib Drug: Placebo Drug: Proton pump inhibitor Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Study of Prophylactic Oral Steroids for Fatigue and Malaise Due to Regorafenib Treatment for Unresectable Metastatic Colorectal Cancer: a Randomized, Placebo-controlled, Double-blind Phase 2 Clinical Study (KSCC1402/HGCSG1402)
Study Start Date : October 2014
Estimated Primary Completion Date : September 2015
Estimated Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fatigue
Drug Information available for: Regorafenib

Arm Intervention/treatment
Active Comparator: Treatment group

Treatment with regorafenib (160 mg/day, oral administration, 3 weeks on therapy followed by 1 week off therapy), test drug capsule (dexamethasone 2 mg) and proton pump inhibitors (PPIs) will be started within 14 days of enrollment. The protocol treatment period is 4 weeks.

Follow-up treatment for the underlying disease after the 4-week protocol treatment is not specified. The physician in charge will decide whether or not to continue treatment with regorafenib. For the prevention of fatigue/malaise, dexamethasone 2 mg can be used.

General condition, blood pressure, Patient Reported Outcome, clinical findings, hematology/blood chemistry, coagulation and fibrinolysis system, urinalysis, medicatiob check, adverse event, thyroid function test, brain MRI, Contrast-enhanced torso CT

Other: General condition
Eastern Cooperative Oncology Group (ECOG) performance status (PS), height and body weight

Other: Blood pressure
systolic blood pressure (SBP)/diastolic blood pressure (DBP)

Other: Patient Reported Outcome
Incidence of fatigue or malaise (All grade of CTCAE ver. 4), anorexia, Brief fatigue inventory (BFI), FACT-C.
Other Name: PRO

Other: Clinical findings
  • Blood and lymphatic system disorders: febrile neutropenia
  • Gastrointestinal disorders: constipation, diarrhea, oral mucositis, nausea, and vomiting
  • General disorders and administration site conditions: fatigue and malaise
  • Immune system disorders: allergic reaction
  • Metabolism and nutrition disorders: anorexia
  • Nervous system disorders: dysgeusia and peripheral sensory neuropathy
  • Respiratory, thoracic and mediastinal disorders: hoarseness (change of voice)
  • Skin and subcutaneous tissue disorders: alopecia, skin hyperpigmentation, urticaria, and palmar-plantar erythrodysesthesia syndrome
  • Vascular disorders: hypertension
  • Symptomatic pancreatitis

Other: Hematology/blood chemistry
White blood cell count, absolute neutrophil count (stab + segmented), hemoglobin, platelet count, albumin, total bilirubin, aspartate aminotransferase(AST) (GOT), alanine aminotransferase (ALT) (GPT), serum creatinine, Na, K

Other: Coagulation and fibrinolysis system
international normalized ratio (INR)

Other: Urinalysis
Proteinuria (qualitative)

Other: Medication check
Medicine taking situation (regorafenib, dexamethasone and placebo) determined by subject's diary at every courses

Other: Adverse event
CTCAE ver.4.0
Other Name: AE

Other: Thyroid function test
Thyroid-stimulating hormone (TSH), T4, and T3

Other: Contrast-enhanced torso CT
It is recommended that CT images should be taken every 4 weeks (if possible) or at least every 8 weeks (allowable time window: ± 2 weeks), with the treatment phase taken into consideration.

Other: Brain MRI
If any symptom of brain metastasis is suspected

Drug: Dexamethasone
Capsule filled with dexamethasone and lactose
Other Name: DX

Drug: Regorafenib
Film-coating tablet contains 40 mg of regorafenib
Other Name: Stivarga

Drug: Proton pump inhibitor
PPIs (omeprazole, lansoprazole, etc, as not specified) for prevention of peptic ulcer
Other Name: PPI

Placebo Comparator: Placebo group

Treatment with regorafenib (160 mg/day, oral administration, 3 weeks on therapy followed by 1 week off therapy), placebo capsule (lactose) and proton pump inhibitors (PPIs) will be started within 14 days of enrollment. The protocol treatment period is 4 weeks.

Follow-up treatment for the underlying disease after the 4-week protocol treatment is not specified. The physician in charge will decide whether or not to continue treatment with regorafenib. For the prevention of fatigue/malaise, dexamethasone 2 mg can be used.

General condition, blood pressure, Patient Reported Outcome, clinical findings, hematology/blood chemistry, coagulation and fibrinolysis system, urinalysis, medication check, adverse event, thyroid function test, brain MRI, Contrast-enhanced torso CT

Other: General condition
Eastern Cooperative Oncology Group (ECOG) performance status (PS), height and body weight

Other: Blood pressure
systolic blood pressure (SBP)/diastolic blood pressure (DBP)

Other: Patient Reported Outcome
Incidence of fatigue or malaise (All grade of CTCAE ver. 4), anorexia, Brief fatigue inventory (BFI), FACT-C.
Other Name: PRO

Other: Clinical findings
  • Blood and lymphatic system disorders: febrile neutropenia
  • Gastrointestinal disorders: constipation, diarrhea, oral mucositis, nausea, and vomiting
  • General disorders and administration site conditions: fatigue and malaise
  • Immune system disorders: allergic reaction
  • Metabolism and nutrition disorders: anorexia
  • Nervous system disorders: dysgeusia and peripheral sensory neuropathy
  • Respiratory, thoracic and mediastinal disorders: hoarseness (change of voice)
  • Skin and subcutaneous tissue disorders: alopecia, skin hyperpigmentation, urticaria, and palmar-plantar erythrodysesthesia syndrome
  • Vascular disorders: hypertension
  • Symptomatic pancreatitis

Other: Hematology/blood chemistry
White blood cell count, absolute neutrophil count (stab + segmented), hemoglobin, platelet count, albumin, total bilirubin, aspartate aminotransferase(AST) (GOT), alanine aminotransferase (ALT) (GPT), serum creatinine, Na, K

Other: Coagulation and fibrinolysis system
international normalized ratio (INR)

Other: Urinalysis
Proteinuria (qualitative)

Other: Medication check
Medicine taking situation (regorafenib, dexamethasone and placebo) determined by subject's diary at every courses

Other: Adverse event
CTCAE ver.4.0
Other Name: AE

Other: Thyroid function test
Thyroid-stimulating hormone (TSH), T4, and T3

Other: Contrast-enhanced torso CT
It is recommended that CT images should be taken every 4 weeks (if possible) or at least every 8 weeks (allowable time window: ± 2 weeks), with the treatment phase taken into consideration.

Other: Brain MRI
If any symptom of brain metastasis is suspected

Drug: Regorafenib
Film-coating tablet contains 40 mg of regorafenib
Other Name: Stivarga

Drug: Placebo
Capsule filled with lactose
Other Name: PL

Drug: Proton pump inhibitor
PPIs (omeprazole, lansoprazole, etc, as not specified) for prevention of peptic ulcer
Other Name: PPI




Primary Outcome Measures :
  1. incidence of fatigue or malaise (CTCAE ver. 4, all grades) [ Time Frame: 4weeks ]
    With the number of subjects in safety analysis set (SAS) as the denominator, the frequency of the worst grade of "fatigue" or "malaise"(according to CTCAE ver.4.0) is determined.


Secondary Outcome Measures :
  1. brief fatigue inventory (Patient Reported Outcome) [ Time Frame: 4weeks ]
    For all subjects enrolled in the present clinical study, the severity of fatigue/malaise is rated using the brief fatigue inventory (BFI) scale obtained every week following the start. Mean of numerical evaluating scale from 9 questions is defined as the global fatigue score. Details of the method to collect and analyze the BFI as a patient reported outcome (PRO) will be specified in a procedure separately prepared along the instruction by Professor Yamaguchi (Tohoku University).

  2. adverse events [ Time Frame: 1year ]

    With the number of subjects in whom at least a part of the protocol treatment is provided (all treated subjects) set as the denominator, the frequencies of the following adverse events/toxicity (according to CTCAE ver.4.0) appearing at the worst grade whenever during the entire treatment course are determined by treatment group. Whether ineligible subjects are included in the analysis set or not is decided by the KSCC's research administration office through discussion with the Registration/Data Center.

    With the number of subjects in Full analysis set (FAS) set as the denominator, the rate of treatment discontinuation due to adverse events other than disease progression is determined.


  3. relative dose intensity (regorafenib) [ Time Frame: 4weeks ]
    With the planned dose of regorafenib in 1 course set as the denominator while the actual dose set as the numerator, the relative dose intensity (given in percentage) is determined for the FAS.


Other Outcome Measures:
  1. medicine taking situation (regorafenib, study drug) [ Time Frame: 4weeks (study drug), 1year (regorafenib) ]
  2. response rate [ Time Frame: 1year ]
    The best response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as the proportion of subjects (among the FAS) whose best overall response is either complete response (CR) or partial response (PR).

  3. disease control rate (DCR) [ Time Frame: 1year ]
    The disease control rate is defined as the proportion of subjects (among the FAS) whose best overall response and confirmed overall response based on RECIST v1.1 are either of CR, PR, or stable disease (SD).

  4. treatment continuation period [ Time Frame: 1year ]
  5. progression-free survival (PFS) [ Time Frame: 1year ]
    For the FAS, the progression-free survival is defined as a period from the day of enrollment to whichever earlier date of exacerbation or death from any cause.

  6. overall survival (OS) [ Time Frame: 1year ]

    Taking the enrollment day as the starting date, the overall survival is defined as time to death for any cause.

    Subjects who are alive are censored for over survival at the date that they are last known to be alive.

    Subjects who lost to follow-up are censored for overall survival at the date that they are last known to be alive.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Capable of granting informed consent in writing for receiving treatment outlined in this protocol
  • The investigators determines that the patient can receive the treatment outlined in this protocol
  • Histological diagnosis of adenocarcinoma of either the colon or the rectum, regardless of RAS mutation
  • Metastatic colorectal cancer scheduled for treatment with regorafenib
  • Lesions are either measurable or non-measurable according to RECIST ver. 1.1
  • Contrasted torso CT within 28 days before enrollment
  • At least 20 years of age
  • PS 0-1
  • Bone marrow, hepatic, and renal functions have all been confirmed as normal within 14 days prior to initiation of regorafenib treatment
  • Life expectancy of at least 3 months

Exclusion Criteria:

  • Used regorafenib previously
  • Blood transfusion or granulocyte-colony stimulating factor (G-CSF) administration within 14 days
  • Grade 2 or higher fatigue or malaise or asthenia according to NCI-CTCAE ver. 4.0
  • History of a different type of cancer according to histological findings or cancer of a different primary focus within the past 5 years. The following are excluded: carcinoma in situ of the cervix, non-melanoma skin cancer, superficial bladder cancer (Ta, Tis, and T1), gastric cancer,non-invasive breast cancer, etc
  • Highly invasive surgery, an open biopsy, or who have received significant trauma within 28 days of initiating regorafenib treatment
  • Congestive cardiac failure of New York Heart Association (NYHA) >=Class 2
  • Unstable angina (symptoms at rest),new-onset angina (onset within past 3 months), or a history of myocardial infarction within 6 months of initiating treatment
  • Arrhythmia requiring treatment with anti-arrhythmia drugs
  • Uncontrollable hypertension
  • Pleural effusion or ascites causing dyspnea (NCI-CTCAE >=Grade 2)
  • History of venous or arterial thrombosis or embolism within 6 months prior to initiation of treatment, including cerebrovascular accidents, deep vein thrombosis, or pulmonary embolism
  • Patients with active infections of NCI-CTCAE >=Grade 3
  • Positive for either hepatitis B (HB)s antigen or hepatitis C virus (HCV) antibody
  • Seizure disorders requiring drug treatment
  • Cerebral metastases or history of such
  • History of organ transplant
  • Symptoms or history of hemorrhagic tendency, regardless of severity
  • Some form of hemorrhaging (NCI-CTCAE >=Grade 2) within 4 weeks prior to initiating treatment
  • Incurable wound, fracture or ulcer
  • Renal failure requiring either hemodialysis or peritoneal dialysis
  • Dehydration symptoms of NCI-CTCAE >=Grade 1
  • Abusing drugs or who are in a physical, psychological, or social state which might impair study participation or evaluation of results
  • Interstitial lung disease with active signs or symptoms
  • Have difficulty taking oral drugs
  • Digestion absorption disorders
  • Adverse events resulting from previous treatments or procedures which have not yet resolved (NCI-CTCAE >=Grade 2)
  • Received systemic anti-cancer treatments within 2 weeks prior to initiation of regorafenib treatment, including chemotherapy, molecular target drugs, immunotherapy, or hormone therapy
  • Poorly controlled glucose tolerance abnormalities due to diabetes mellitus (patients using insulin)
  • Active GI ulcers or a history of such
  • Glaucoma
  • Oral steroids are otherwise contraindicated
  • Either pregnant or nursing. Women who may become pregnant must have a negative pregnancy test within 7 days prior to initiating treatment
  • Women who may become pregnant, or men whose partners may become pregnant, must agree to use appropriate contraceptives from granting of consent to 3 months after conclusion of regorafenib therapy
  • Other illnesses or conditions which, according to the judgment of the investigator, may result in physical harm caused by the study, or which may impair study compliance

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02288078


Contacts
Layout table for location contacts
Contact: Yuji Miyamoto, MD, PhD miyamotoyuji@gmail.com
Contact: Yasunori Emi, MD, PhD emi-y@saiseikai-hp.chuo.fukuoka.jp

Locations
Layout table for location information
Japan
Saiseikai Fukuoka General Hospital Recruiting
Fukuoka, Japan, 810-0001
Contact: Yasunori Emi, MD, PhD    +81-92-771-8151    emi-y@saiseikai-hp.chuo.fukuoka.jp   
Sponsors and Collaborators
Clinical Research Support Center Kyush
Investigators
Layout table for investigator information
Study Director: Yasunori Emi, MD, PhD Saiseikai Fukuoka General Hospital
Layout table for additonal information
Responsible Party: Hideo Baba, Professor, Kumamoto University
ClinicalTrials.gov Identifier: NCT02288078    
Other Study ID Numbers: KSCC1402/HGCSG1402
UMIN000015131 ( Registry Identifier: University Hospital Information Network )
First Posted: November 11, 2014    Key Record Dates
Last Update Posted: November 13, 2014
Last Verified: November 2014
Keywords provided by Hideo Baba, Kumamoto University:
unresectable colorectal cancer
regorafenib
Steroid
fatigue and malaise
Phase 2 randomized, controlled trial (RCT)
Additional relevant MeSH terms:
Layout table for MeSH terms
Fatigue
Signs and Symptoms
Dexamethasone
Proton Pump Inhibitors
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action