A randomised phase II trial of imatinib alternating with regorafenib compared to imatinib alone for the first line treatment of advanced gastrointestinal stromal tumour (GIST)
- Conditions
- Metastatic gastrointestinal stromal tumour (GIST)Cancer - Sarcoma (also see 'Bone') - soft tissue
- Registration Number
- ACTRN12614000950662
- Lead Sponsor
- Australasian Gastro-Intestinal Trials Group (AGITG)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 78
Adults (over 18 yrs) with histologically confirmed GIST. In CD-117-negative cases DOG-1 must be positive or a KIT/PDGFRA mutation must be present.
-Unresectable, metastatic disease.
-No prior TKI for metastatic disease, with the exception of those patients who have had up to 21 days of uninterrupted treatment on 400mg daily of imatinib.
-Imatinib therapy given as an adjuvant treatment and completed at least 3 months prior to entry into this trial is permitted. Patients who have progression of GIST while on adjuvant therapy are not eligible for this trial.
-ECOG performance status 0-2
-Measurable disease by RECIST version 1.1. (Note: Participants with only peritoneal disease will be eligible only if they have lesions measurable in two dimensions and have at least 1 lesion which is greater than or equal to 2 cm in size).
-Adequate bone marrow function (Haemoglobin greater than or equal to 9.0g/dL, platelet count greater than or equal to 100 x 109/L, and absolute neutrophil count greater than or equal to 1.5 x 109/L).
Adequate liver function (Serum total bilirubin less than or equal to 1.5 x ULN, INR less than or equal to 1.5, and ALT, AST, ALP less than or equal to 2.5 x ULN (less than or equal to 5 x ULN for participants with liver metastases). Lipase level must be less than or equal to 1.5 x ULN.
Adequate renal function (Creatinine clearance greater than 50ml/min) based on either the Cockcroft Gault formula, 24 hour urine or Glomerular Filtration Rate (GFR scan); and serum creatinine less than or equal to 1.5 x ULN.
-Tumour tissue available for central review.
-Willing and able to comply with all study requirements, including treatment timing and/or nature of required assessments.
-Study treatment both planned and able to start within 14 days of randomisation.
-Signed, written informed consent.
-Concurrent GI illness which may prevent absorption of imatinib or regorafenib – please note that prior gastrectomy or bowel resection does not exclude patients from this study.
-Use of other investigational drugs within 4 weeks prior to enrolment.
-Known sensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
-Participants receiving therapeutic doses of warfarin.
-Presence of brain metastases.
-The presence of PDGFR D842V mutation or other mutation known to cause imatinib resistance.
- Inability to swallow tablets.
-Arterial thrombotic or ischaemic events, such as cerebrovascular accident or pulmonary embolism within 6 months prior to randomisation; or major venous thrombotic events requiring use of an anticoagulant such as warfarin within 6 months prior to randomisation.
-Poorly controlled hypertension (systolic blood pressure greater than 140 mmHg or diastolic pressure greater than 90 mmHg despite optimal medical management).
-Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomisation, or non healing wound, ulcer or fracture.
-Congestive cardiac failure (NYHA greater than or equal to grade 2), unstable angina or new onset angina within the previous 3 months, or AMI within the previous 6 months. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
-Haemorrhage or bleeding event greater than or equal to Grade 3 according to CTCAE v4.0 within 4 weeks prior to randomisation.
-Ongoing infection of greater than Grade 2 according to CTCAE v4.0.
-Active hepatitis B or C or HIV, or chronic hepatitis B or C requiring treatment with antiviral therapy. Testing for these is not mandatory unless clinically indicated.
-Interstitial lung disease with ongoing signs and symptoms.
-Persistent proteinuria of greater than or equal to Grade 3 (greater than 3.5g/24 hours) according to CTCAE v4.0
-Other significant medical or psychiatric condition judged by the investigator to interfere with protocol requirements.
-Use of biological response modifiers such as granulocyte colony stimulating factor (G-CSF), within 3 weeks prior to randomisation.
-Patients taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinovir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg carbamazepine, phenobarbitol, phenytoin, rifampicin, St John’s wort).
-History of another malignancy within 5 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment.
- Pregnancy, lactation, or inadequate contraception. Women must be post menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Women of childbearing potential and men must agree to use adequate contraception before entering the trial until at least 8 weeks after the last study drug administration.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method