1st-line Activity of Dovitinib and Correlation With Genetic Changes in RCC

• Status: Unknown status
• Trial end date: 2015-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The main purpose of this study is to find out how useful dovitinib is when given as the initial treatment to participants with advanced kidney cancer, that has spread to other parts of the body. The usefulness of dovitinib will be assessed by: how long the disease is controlled while participants are receiving the drug, the proportion of participants who get a reduction in the size of their tumours and how long participants live (both while on dovitinib and on any subsequent therapy they may receive).

If participants have secondary disease in the bones, the study will evaluate how useful dovitinib is in controlling this site of disease. In addition, this study will look for changes in the genetic makeup of tumour cells and see if some of these changes are associated with a benefit from dovitinib. The study will also compare and contrast the genetic changes in the primary tumour cells with cells from secondary tumour specimens, and with cells from tumour specimens taken if a participant's disease has worsened. The purpose of the latter is to identify possible ways in which the tumour becomes resistant to the study drug.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Auckland District Health Board
• Collaborators: IGENZ, Ltd., Auckland; Novartis; University of Auckland, New Zealand

Criteria

Inclusion Criteria:

• Advanced renal cell (clear cell) carcinoma confirmed histologically, including either distant metastases or locally advanced disease that is not resectable or potentially resectable following response. Sarcomatoid change is allowed if clear cell predominant. Histological variants, papillary, chromophobe and collecting duct carcinoma are not allowed.

• Availability of FFPE tissue for gene status analysis. If unavailable, an image-guided biopsy of a metastatic disease site is required.

• Evaluable disease by RECIST 1.1 criteria

• ECOG (WHO) performance status 0 or 1

• Age ≥ 18 years

• Absolute neutrophil count ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; haemoglobin > 9 g/dL; serum total bilirubin ≤ 1.5 x ULN; ALT and AST ≤ 3.0 x ULN; serum creatinine ≤ 1.5 x ULN or creatinine clearance >35 ml/min by Cockcroft and Gault.

Exclusion Criteria:

• Uncontrolled brain metastases. For know brain metastases, definitive treatment with either surgery, stereotactic radiotherapy or whole brain radiotherapy is required. Patients must be neurologically stable for > 4 weeks after CNS treatment ends, and either be off corticosteroids or receiving a low daily dose.

• Another primary malignancy within 3 years prior to starting study treatment, except for adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix. If another primary tumour was noted within this period, a metastatic disease site biopsy is required to confirm renal origin.

• Prior systemic anticancer treatment for renal carcinoma. Prior bisphosphonates are allowed.

• Radiotherapy ≤ 4 weeks prior to starting the study drug or non-recovery from related toxicities. Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study drug is allowed.

• Major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic) ≤ 4 weeks prior to starting study treatment or non-recovery from surgical side effects.

• History of pulmonary embolism or untreated deep venous thrombosis within the past 6 months. If a history of PE or DVT within the past 6 months is present, patients must be clinically stable on appropriate doses of anticoagulation as per thrombosis specialist advice.

• Impaired cardiac function or clinically significant cardiac diseases, including history of serious uncontrolled ventricular arrhythmias; clinically significant resting bradycardia; LVEF assessed by 2-D echocardiogram < 50% or lower limit of normal (whichever is higher) or multiple gated acquisition scan < 45% or lower limit of normal (whichever is higher). Within 6 months prior to starting study drug: myocardial infarction, severe/unstable angina, coronary artery bypass graft, congestive heart failure, cerebrovascular accident, transient ischemic attack; uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 90 mm Hg, with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication is allowed before study entry.

• Impaired gastrointestinal function or GI disease that may significantly alter dovitinib absorption, e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection.

• Cirrhosis, chronic active hepatitis or chronic persistent hepatitis

• Known diagnosis of human immunodeficiency virus infection (testing is not mandatory)

• Current full dose anticoagulation treatment with therapeutic doses of warfarin, dabigatran or anti-platelet therapy. Treatment with ≤ 100mg acetylsalicyclic acid daily is allowed as are therapeutic or prophylactic doses of low molecular weight heparin, provided there is no recent evidence of bleeding.

• Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. infection, diabetes) that could cause unacceptable safety risks or compromise protocol compliance.

• Pregnant or breast-feeding women

• Women of child-bearing potential or fertile males not using effective contraception.