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

NCT02288078 | Unknown Phase 2 DMC

• 2 other identifiers: KSCC1402/HGCSG1402UMIN000015131
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Cancer

Keywords

unresectable colorectal cancer; regorafenib; Steroid; fatigue and malaise; Phase 2 randomized, controlled trial (RCT)

Outcome Measures

Primary Outcomes (1)

• incidence of fatigue or malaise (CTCAE ver. 4, all grades)

  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.

  4weeks

Secondary Outcomes (3)

• brief fatigue inventory （Patient Reported Outcome）

  4weeks

• adverse events

  1year

• relative dose intensity (regorafenib)

  4weeks

Other Outcomes (6)

• medicine taking situation (regorafenib, study drug)

  4weeks (study drug), 1year (regorafenib)

• response rate

  1year

• disease control rate (DCR)

  1year

Study Arms (2)

Treatment group

ACTIVE COMPARATOR

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; 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: Proton pump inhibitor

Placebo group

PLACEBO COMPARATOR

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; 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: Regorafenib; Drug: Placebo; Drug: Proton pump inhibitor

Interventions

General condition OTHER

Eastern Cooperative Oncology Group (ECOG) performance status (PS), height and body weight

Placebo group; Treatment group

Blood pressure OTHER

systolic blood pressure (SBP)/diastolic blood pressure (DBP)

Placebo group; Treatment group

Patient Reported Outcome OTHER

Incidence of fatigue or malaise (All grade of CTCAE ver. 4), anorexia, Brief fatigue inventory (BFI), FACT-C.

Also known as: PRO

Placebo group; Treatment group

Clinical findings OTHER

* 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

Placebo group; Treatment group

Hematology/blood chemistry OTHER

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

Placebo group; Treatment group

Coagulation and fibrinolysis system OTHER

international normalized ratio (INR)

Placebo group; Treatment group

Urinalysis OTHER

Proteinuria (qualitative)

Placebo group; Treatment group

Medication check OTHER

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

Placebo group; Treatment group

Adverse event OTHER

CTCAE ver.4.0

Also known as: AE

Placebo group; Treatment group

Thyroid function test OTHER

Thyroid-stimulating hormone (TSH), T4, and T3

Placebo group; Treatment group

Contrast-enhanced torso CT OTHER

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.

Placebo group; Treatment group

Brain MRI OTHER

If any symptom of brain metastasis is suspected

Placebo group; Treatment group

Dexamethasone DRUG

Capsule filled with dexamethasone and lactose

Also known as: DX

Treatment group

Regorafenib DRUG

Film-coating tablet contains 40 mg of regorafenib

Also known as: Stivarga

Placebo group; Treatment group

Placebo DRUG

Capsule filled with lactose

Also known as: PL

Placebo group

Proton pump inhibitor DRUG

PPIs (omeprazole, lansoprazole, etc, as not specified) for prevention of peptic ulcer

Also known as: PPI

Placebo group; Treatment group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Clinical Research Support Center Kyush: lead

Study Sites (1)

Saiseikai Fukuoka General Hospital

Fukuoka, 810-0001, Japan

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms; Fatigue

Interventions

Blood Pressure; Patient Reported Outcome Measures; Hematologic Tests; Blood Chemical Analysis; Blood Coagulation; Urinalysis; Dexamethasone; regorafenib; Proton Pump Inhibitors

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vital Signs; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Health Care Surveys; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Services Research; Health Planning; Health Care Economics and Organizations; Patient Outcome Assessment; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Health Care Evaluation Mechanisms; Public Health; Environment and Public Health; Clinical Laboratory Techniques; Clinical Chemistry Tests; Hemostasis; Blood Physiological Phenomena; Diagnostic Techniques, Urological; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Yasunori Emi, MD, PhD

  Saiseikai Fukuoka General Hospital

  STUDY DIRECTOR

Central Study Contacts

Yuji Miyamoto, MD, PhD

CONTACT

miyamotoyuji@gmail.com

Yasunori Emi, MD, PhD

CONTACT

emi-y@saiseikai-hp.chuo.fukuoka.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: November 11, 2014
• Study Start: October 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2016
• Last Updated: November 13, 2014

Record last verified: 2014-11

Locations

JP (1)