A Multicenter Phase I/II Study of Cabozantinib Alone or in Combination with Panitumumab in Patients with MET-amplified metastatic colorectal cancer
METBEIGE Study
National Cancer Center Hospital East
6-5-1 Kashiwanoha,Kashiwa,Chiba,Japan 277-8577
+81-4-7133-1111
metbeige_core@east.ncc.go.jp
National Cancer Center Hospital East
6-5-1 Kashiwanoha,Kashiwa,Chiba,Japan 277-8577
+81-4-7133-1111
metbeige_core@east.ncc.go.jp
completed
April. 22, 2019
54
Interventional
An open-label, single arm phase I study and an open-label, randomized controlled multicenter phase II study
treatment purpose
1-2
1. Informed consent for participation in the study is obtained at the discretion of the patient.
2. RAS and BRAF V600E gene wild types as determined by tumor tissue assay
3. Phase 1 part only: RAS and BRAF V600E gene wild types as determined by liquid biopsy assay in cases of prior treatment with anti-EGFR antibody
4. Phase 2 part only: Patients with MET amplification as determined by liquid biopsy analysis
5. Phase 1 part only: Patients not responding to, or not tolerating, at least one regimen of chemotherapy containing fluoropyrimidine drugs, oxaliplatin, and irinotecan in treatment for mCRC (irrespective of whether an anti-EGFR antibody was administered, and irrespective of whether an anti-VEGF antibody was administered).
6. Phase 2 part only: Patients not responding to, or not tolerating, at least one chemotherapy regimen (including irinotecan or oxaliplatin) containing fluoropyrimidine drugs in treatment for mCRC (irrespective of whether an anti-VEGF antibody was administered).
7. Phase 2 part only: Patients who did not respond to anti-EGFR antibody drug (either panitumumab or cetuximab)
1. History of prior monoclonal antibody, chemotherapy, targeted small molecule therapy within 2 weeks prior to study Day 1 or not recovered (i.e., not greater than Grade 1 or at baseline) from adverse events due to a previously administered agent
2. History of surgical treatment and radiotherapy within 2 weeks before enrollment
3. Symptomatic brain metastases or meningeal dissemination
4. Inadequately controlled hypertension
5. Known acute or chronic pancreatitis
6. Medical history of clinically significant cardiac diseases
7. Gastrointestinal function or gastrointestinal diseases that significantly interfere with absorption, distribution, metabolism, and excretion of the study drugs
8. History of other malignant tumors within 3 years before enrollment in the study
9. Medical history of thromboembolism within 6 months
10. Concomitant anticoagulation, with oral anticoagulants or platelet inhibitors
11. Interstitial lung disease with symptoms or signs of activity
12. Known allergy or hypersensitivity to any of the components of cabozantinib tablets
13. History of abdominal fistula and/or gastrointestinal perforation within 6 months before enrollment.
14. Non-healing wound, non-healing ulcer, or non-healing bone fracture
15. Any hemorrhage or bleeding event, greater than or equal to CTCAE Grade 3, within 4 weeks before enrollment
16. Cavitating pulmonary lesions or known endobronchial disease manifestation
17. Lesions invading major pulmonary blood vessels
20age old over
No limit
Both
colorectal cancer
investigational material(s)
Generic name etc : Cabozantinib Malate
INN of investigational material : Cabozantinib
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : Cabozantinib: 40 mg or 60 mg, once daily at bedtime, oral, in a 28 day-course.
control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -
safety
efficacy
- Proportion of subjects with DLT (phase 1 part)
- Confirmed ORR by investigators' assessment in patients who received study treatment as 3rd line or later (phase 2 part)
safety
efficacy
- Progression-free survival (PFS)
- Duration of response (DoR)
- Disease control rate (DCR)
- Overall survival (OS)
- Confirmed ORR by investigators' assessment in patients who received study treatment as 2nd line (phase II part)
- Confirmed ORR by investigators' assessment in patients who received study treatment as 2nd line and 3rd line or later (phase 2 part)
- Confirmed ORR/DCR by central assessment
- Proportion of patients with adverse events
