Kidney Cancer
Conditions
Brief summary
The purpose of this study is to determine whether the combination of bevacizumab/temsirolimus is effective in patients with advanced renal carcinoma progressing after anti-VEGF treatment
Interventions
DRUGBevacizumab
Bevacizumab 10mg/kg intravenous every 2 weeks until disease progression, unacceptable toxicity or consent withdrawal.
DRUGTemsirolimus
Temsirolimus 25mg intravenous once weekly until disease progression, unacceptable toxicity or consent withdrawal.
Sponsors
Hellenic Cooperative Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (18th year of age completed) * Signed and dated written informed consent form prior to any procedures related to this protocol. * Histologically confirmed advanced clear cell renal cancer. * Measurable disease. * Failure of first line anti-VEGF treatment. * Performance status 0-2, according to Eastern Cooperative Oncology Group (ECOG) . * Satisfactory hematological parameters: * White blood cell count \> 4000 mm3. * Platelet count 100000/mm3. * Neutrophil blood cell count \> 1200/ mm3 . * Hemoglobin \> 9,0 g/dL (can be achieved with red blood cell transfusion). * Satisfactory biochemical parameters: * Serum creatinine \< 2 x Upper Limit of Normal(ULN) * Aspartate Aminotransferase (AST)\<2,5 x ULN * Alanine Transaminase (ALT)\< 2,5 x ULN. * Bilirubin \<2 x ULN * (For female patients) Absence of pregnancy (negative pregnancy test for women of reproductive age before enrollment). * (For female patients) Non-lactating women. * Use of efficient contraceptive measures (women and men) to prevent possible pregnancy of female patient or female partner of a male patient during treatment and until 6 months after the end of treatment.
Exclusion criteria
* Prior treatment with mTOR inhibitor. * Major surgery (including open biopsy) or insufficient recovery or existence of major trauma within 4 weeks before enrollment. * Uncontrolled hypertension. * Active infection requiring systemic treatment within 4 weeks prior to enrollment. * Minor surgery (for instance, catheter placement) within 2 days before enrollment. * Scheduled major surgery within the treatment period. * Medical history in the last 6 months prior to enrollment of significant cardiovascular disease, diabetes, cardiac infarction, unstable angina, uncontrolled arrhythmia or significant heart failure. * Indications of uncontrolled metastases or disease progression in CNS lesions (the suspicion of uncontrolled metastases or disease progression should be eliminated by imaging techniques within 14 days prior to enrollment). * Medical history in the last 5 years prior to enrollment of any other malignancies (excluding the basal or squamous skin cell carcinoma or in situ carcinoma of the cervix). * History of non-healing wound including active gastric ulcer. * History of fistula in the last 6 months prior to enrollment. * History of gastrointestinal perforations. * Patient incapacity (for psychiatric or social reasons) to conform with the protocol. * History of hemorrhagic predisposition. * History of hypersensitivity to the medications under investigation. * Significant proteinurea. * Prior immunotherapy within 4 weeks prior to enrollment. * Prior radiation treatment within 2 weeks prior to enrollment. * Concomitant medication with inducers or strong inhibitors of the coenzyme CYP3A4 (see Appendix 5 for an indicative list of active compounds). * Concurrent participation in other interventional clinical trials with investigational medicinal products. * History of chronic interstitial lung disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-month Progression Free Survival (PFS) | 32 months | Proportion of patients who are progression-free at 6month evaluation from treatment initiation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 48 months | OS will be calculated from the date of treatment initiation to the date of death or last contact |
| Response Rate (RR) | Tumor assessments will be performed every 8 weeks during treatment and at discontinuation, unless it was performed within the last 4 weeks | RR is defined as the overall percentage of patients with partial (PR) or complete response (CR). The evaluation of responses will be performed according to RECIST criteria |
| Tumor Shrinkage | Tumor assessments will be performed every 8 weeks during treatment and at discontinuation, unless it was performed within the last 4 weeks | Tumor shrinkage will be computed using waterfall plots |
| Progression Free Survival (PFS) | Tumor assessments will be performed every 8 weeks during treatment and at discontinuation, unless it was performed within the last 4 weeks | PFS will be calculated from date of treatment initiation until disease progression or death (whichever occurs first) |
| Quality of Life (QoL) assessment | At baseline and every 8 weeks during treatment | QoL will be assessed using the EORTC QLQ C-30 questionnaire. The change in the QoL during treatment will be estimated using the Wilcoxon paired t-test |
| Investigation of antiangiogenic factors (FGF, VEGF, VEGFRR) | 36 months | Changes in serum levels of antiangiogenic factors during treatment and correlation to the outcome of study treatment. |
| Adverse Events (AEs) of all participants will be recorded and assessed upon signature of the informed consent form, until 30 days after the last administration of study treatment. | 3 years | Adverse Events will be graded according to the NCI CTCAE v3.0 criteria and will be reported in a frequency table according to the highest severity grade observed per patient |
Countries
Greece
Outcome results
None listed