Phase II study of cabozantinib in patients with metastatic gastrointestinal stromal tumor (GIST) who progressed during neoadjuvant, adjuvant or palliative therapy with imatinib and sunitinib
- Conditions
- metastatic gastrointestinal stromal tumor (GIST)MedDRA version: 20.0Level: LLTClassification code 10062427Term: Gastrointestinal stromal tumorSystem Organ Class: 100000016768Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-000501-13-DE
- Lead Sponsor
- European Organisation for Research and Treatment of Cancer (EORTC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 41
?Histologically confirmed diagnosis of GIST that is metastatic.
? Presence of at least one non-previously irradiated, measurable metastatic lesion as defined by RECIST 1.1
?Radiographic absence of a cavitating pulmonary lesion within 28 days prior to the first dose of cabozantinib
?Consent of the patient
?Failure on prior therapy with imatinib and sunitinib
?Male or female patient = 18 years of age
?ECOG performance status (PS) of 0-1
?Adequate bone marrow and organ function prior to receiving the first dose of study treatment
?Clinically normal cardiac function
?Patients must be able to swallow and retain oral film-coated tablets
?Recovery to baseline or = Grade 1 CTCAE v.4.0 from toxicities related to any prior treatments
?Prior radiation therapy patients with clinically relevant ongoing complications from prior radiation therapy are not eligible
?Prior surgery:
- minor surgery within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment is permitted
- Patients with clinically relevant ongoing complications from prior surgery are not eligible
? Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
? Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
?Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
?Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 4 months after the last study treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:
? Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
? Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
? Intrauterine device (IUD)
? Intrauterine hormone-releasing system (IUS)
? Bilateral tubal occlusion
? Vasectomized partner
? Sexual abstinence
?Before patient registration, written informed consent must be given according to international conference on harmonization/Good clinical practice (ICH/GCP), and national/local regulations.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35
?evidence of tumor or metastatic lesion invading the gastrointestinal tract within 28 days prior to the first dose of cabozantinib
?current evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
?Patient with tumor in contact with, invading or encasing a major blood vessel
?Prior use of tyrosine kinase inhibitors for the treatment of advanced GIST with the exception of imatinib and sunitinib
?Other investigational agents within 28 days before the first dose of study treatment
?History of congenital long QT syndrome
?QTcF> 500 msec within 1 month before the first dose of study treatment
?Congestive heart failure
?History of unstable angina, clinically significant cardiac arrhythmias and myocardial infarction within 6 months prior to the first dose of protocol treatment
?Poorly controlled hypertension
?Concomitant anticoagulation at therapeutic doses with oral anticoagulants
?Specific contraindications for treatment with cabozantinib
?stroke and thromboembolic event requiring therapeutic anticoagulation within 6 months before the first dose of study treatment
?Gastrointestinal disorders associated with a high risk of perforation or fistula formation
?other clinically significant disorders that would preclude safe study participation.
?Evidence of significant active bleeding or bleeding diathesis within 6 months before the first dose of study treatment
?Hemoptysis = 0.5 teaspoon of red blood within 3 months before the first dose of study treatment
?Signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
?Prior radiation therapy:
-radiation therapy for bone metastasis within 2 weeks, or any other external radiation therapy within 4 weeks before the first dose of study treatment.
-systemic treatment with radionuclides within 6 weeks before the first dose of study treatment.
?Prior surgery major surgery or trauma within 12 weeks prior to first dose of study drug and/or presence of any non-healing wound, fracture or ulcer.
? Active infection requiring systemic treatment within 28 days before the first dose of study treatment.
? History of organ transplant.
? Concurrent severe, clinically relevant hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
?History of other malignancy in the past 5 years with the exception of treated carcinoma in situ of the cervix and non-metastatic, non-melanoma skin cancer
?Patients requiring chronic concomitant treatment with strong Cytochrome P450 (CYP) 3A4 inducers
?Lactating females
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method