Colorectal cancer
Conditions
Interventions
sequential treatment with regorafenib followed by cetuximab +/- irinotecan
sequential treatment with cetuximab +/- irinotecan followed by regorafenib
Sponsors
REVERCE study group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Histologically proven, unresectable distant metastatic or locally advanced colorectal adenocarcinoma 2)No KRAS mutation (codon 12 & 13) (i,e, wild-type KRAS): KRAS test will be performed at the study site or an external institution using an appropriate technique such as direct-sequence, Scorpions and ARMS, TaqMan Mutation Detection Assays or Luminex. 3)-5)PD or intolerable to chemotherapy including fluoropyrimidine*, L-OHP* and CPT-11 * * Disease progression or intolerable to chemotherapy are defined as those who meet any of the following: i)Radiographically confirmed recurrence during or within 6 months after adjuvant therapy ii)Radiographically or clinically confirmed disease progression during or within 3 months after chemotherapy for advanced cancer iii)Unacceptable toxicity precluding resumption of treatment 6) Evaluable lesion(s) a) Measurable lesion(s) is not mandatory b) Excluding patients with only body cavity fluid, bone metastasis, skin metastasis, pulmonary lymphangiosis, radiographically undetectable abdominal mass, or cystic lesion 7)>= 20 years at the time of informed consent 8)ECOG PS: 0-1 9)Adequate organ functions within 7 days before enrollment (excluding blood transfusion or hematopoietic factor preparations such as G-CSF within 14 days before enrollment) -Neutrophil count: >= 1500/mm3 -Hb: >=8.0 g/dL (blood transfusion more than 2 weeks before is allowed) -Plt count:>7.5 x 104/mm3 -AST, ALT: <= ULN x 2.5 <= ULN x 5 in patients with liver metastasis) -Total bilirubin: <= ULN x 1.5 -Creatinine: <= 1.5 mg/dL -Protein urine i) Protein urine (urine dipstick) <= 2+ or ii) UPC ratio <3.5 or iii)24-hour protein urine <= 3500 mg -PT-INR: <= ULN x 1.5 (<= x3in the subjects with anticoagulants) 10)Expected to survive for at least 60 days after entry 11)At least 2 weeks of washout from previous radiotherapy and/or chemotherapy for the underlying disease 12)Written consent after detailed explanation of the study before entry including consent for QOL and BMs
Exclusion criteria
Exclusion criteria: 1)Previous treatment with regorafenib, anti-EGFR antibody (cetuximab/panitumumab) or participation in clinical trial for regorafenib 2)Poorly controlled hypertension (SBP>150 mmHg or DBP >90 mmHg despite appropriate treatment) 3)Unstable angina, myocardial infarction, brain infarction, or pulmonary embolism within 6 months before entry 4)Body cavity fluid (e.g., pleural effusion, ascites, pericardial fluid) requiring intervention 5)Local or systemic active infection (grade 3 or higher according to the CTCAE ver. 4) requiring intervention 6)Symptomatic brain metastasis or brain metastasis requiring regular medication (e.g., mannitol, steroids, antiepileptic drugs) 7)Intestinal paralysis or severe gastrointestinal obstruction 8)Patients unable to swallow oral medications 9)Grade 3 or higher hemorrhage within 4 weeks before entry 10)History or clear evidence in CT scanof extensive interstitial pulmonary disease (e.g., interstitial pneumonia, pulmonary fibrosis) 11)Heart failure &#8805; NYHA II 12)History of meningitis carcinomatosis, uncontrollable seizures (status epilepticus, intractable epilepsy), clinically significant mental disorder, or central nerve disorder 13)Active hepatitis B or C 14)Other active malignancies that may affect the prognosis 15)Pregnant or possibly pregnant women, lactating women, or patients unwilling to use adequate contraception 16)Uncontrolled diarrhea (diarrhea interfering with daily life despite appropriate treatment) 17)Unhealed wound (excluding central venous port), ulcer, or bone fracture 18)Any major surgery. open biopsy or traumatic injury within 28 days before enrollment (excluding the same day of the week 4 weeks ago) or colostomy without intestinal resection within 14 days before enrollment 19)Daily systemic steroid treatment (for such as collagen disease) 20)Known hypersensitivity to study drugs, study drug classes, or excipients in the formulation 21)Patients who, in the opinion of the investigator, are inappropriate for the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | — |
Secondary
| Measure | Time frame |
|---|---|
| time to sequential treatment failure (TTF), progression-free survival (PFS) of sequential therapy, PFS of Treatment 1 and Treatment 2, response rate of Treatments 1 and Treatment 2, disease control rate of Treatments 1 and Treatment 2, incidence of adverse events , pateints reported outcome of QOL | — |
Countries
Japan
Contacts
Public ContactKohei Shitara
National Cancer Center Hospital East Department of Gastroenterology and Gastrointestinal Oncology
Outcome results
None listed