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: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-000501-13-HU
- 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