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Efficacy and Safety of Bevacizumab/Temsirolimus Combination to Treat Advanced Renal Cell Carcinoma

Phase 2
Terminated
Conditions
Kidney Cancer
Interventions
Registration Number
NCT01264341
Lead Sponsor
Hellenic Cooperative Oncology Group
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

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
39
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Bevacizumab combined with temsirolimusTemsirolimusBevacizumab 10mg/kg intravenous every 2 weeks Temsirolimus 25mg intravenous once weekly
Bevacizumab combined with temsirolimusBevacizumabBevacizumab 10mg/kg intravenous every 2 weeks Temsirolimus 25mg intravenous once weekly
Primary Outcome Measures
NameTimeMethod
6-month Progression Free Survival (PFS)32 months

Proportion of patients who are progression-free at 6month evaluation from treatment initiation

Secondary Outcome Measures
NameTimeMethod
Quality of Life (QoL) assessmentAt 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

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

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.

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)

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 ShrinkageTumor 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

Trial Locations

Locations (8)

Agii Anargiri Cancer Hospital, 2nd Dept of Medical Oncology

🇬🇷

Athens, Greece

Agii Anargiri Cancer Hospital, 3rd Dept of Medical Oncology

🇬🇷

Athens, Greece

Papageorgiou General Hospital

🇬🇷

Thessaloniki, Greece

General Hospital of Athens "Hippokratio"

🇬🇷

Athens, Greece

University Hospital of Patras

🇬🇷

Rio, Patras, Greece

Metropolitan Hospital, 1st Dept of Medical Oncology

🇬🇷

Athens, Greece

General Peripheral Hospital of Athens "Alexandra"

🇬🇷

Athens, Greece

Metropolitan Hospital, 2nd Dept of Medical Oncology

🇬🇷

Athens, Greece

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