Clinical trial NCT01264341: Efficacy and Safety of Bevacizumab/Temsirolimus Combination to Treat Advanced Renal Cell Carcinoma
Official title: Phase II Study of Efficacy and Safety of Bevacizumab in Combination With Temsirolimus, After 1st Line Anti-VEGF Treatment in Patients With Advanced Renal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Kidney Cancer
Lead sponsor: Hellenic Cooperative Oncology Group
Sponsor class: OTHER
First posted: 2010-12-21
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: 6-month Progression Free Survival (PFS)
timeFrame: 32 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Tumor assessments will be performed every 8 weeks during treatment and at discontinuation, unless it was performed within the last 4 weeks
measure: Overall Survival (OS)
timeFrame: 48 months
measure: Response Rate (RR)
timeFrame: Tumor assessments will be performed every 8 weeks during treatment and at discontinuation, unless it was performed within the last 4 weeks
measure: Tumor Shrinkage
timeFrame: Tumor assessments will be performed every 8 weeks during treatment and at discontinuation, unless it was performed within the last 4 weeks
measure: 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.
timeFrame: 3 years
measure: Quality of Life (QoL) assessment
timeFrame: At baseline and every 8 weeks during treatment
measure: Investigation of antiangiogenic factors (FGF, VEGF, VEGFRR)
timeFrame: 36 months
Other outcomes:
Locations:
city: Athens
country: Greece
facility: General Hospital of Athens "Hippokratio"
city: Athens
country: Greece
facility: General Peripheral Hospital of Athens "Alexandra"
city: Athens
country: Greece
facility: Agii Anargiri Cancer Hospital, 2nd Dept of Medical Oncology
city: Athens
country: Greece
facility: Agii Anargiri Cancer Hospital, 3rd Dept of Medical Oncology
city: Athens
country: Greece
facility: Metropolitan Hospital, 1st Dept of Medical Oncology
city: Athens
country: Greece
facility: Metropolitan Hospital, 2nd Dept of Medical Oncology
city: Rio, Patras
country: Greece
facility: University Hospital of Patras
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital
Study officials:
affiliation: General Peripheral Hospital of Athens "Alexandra", Medical School, University of Athens
name: Aristotelis Bamias, MD, PhD
role: STUDY_CHAIR
References:
citation: Bamias A, Karavasilis V, Gavalas N, Tzannis K, Samantas E, Aravantinos G, Koutras A, Gkerzelis I, Kostouros E, Koutsoukos K, Zagouri F, Fountzilas G, Dimopoulos MA. The combination of bevacizumab/temsirolimus after first-line anti-VEGF therapy in advanced renal-cell carcinoma: a clinical and biomarker study. Int J Clin Oncol. 2019 Apr;24(4):411-419. doi: 10.1007/s10147-018-1361-9. Epub 2018 Oct 29.