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

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

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

Study Overview

• Status: Terminated
• Conditions: Kidney Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Temsirolimus

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11528
    • General Peripheral Hospital of Athens "Alexandra"
  • Athens, Greece, 18547
    • Metropolitan Hospital, 1st Dept of Medical Oncology
  • Athens, Greece, 18547
    • Metropolitan Hospital, 2nd Dept of Medical Oncology
  • Athens, Greece, 14564
    • Agii Anargiri Cancer Hospital, 3rd Dept of Medical Oncology
  • Athens, Greece, 11527
    • General Hospital of Athens "Hippokratio"
  • Athens, Greece, 14564
    • Agii Anargiri Cancer Hospital, 2nd Dept of Medical Oncology
  • Rio, Patras, Greece, 26500
    • University Hospital of Patras
  • Thessaloniki, Greece, 56429
    • Papageorgiou General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab combined with temsirolimus; Bevacizumab 10mg/kg intravenous every 2 weeks Temsirolimus 25mg intravenous once weekly	Drug: Bevacizumab; Bevacizumab 10mg/kg intravenous every 2 weeks until disease progression, unacceptable toxicity or consent withdrawal.; Drug: Temsirolimus; Temsirolimus 25mg intravenous once weekly until disease progression, unacceptable toxicity or consent withdrawal.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month Progression Free Survival (PFS)	Proportion of patients who are progression-free at 6month evaluation from treatment initiation	32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS will be calculated from date of treatment initiation until disease progression or death (whichever occurs first)	Tumor assessments will be performed every 8 weeks during treatment and at discontinuation, unless it was performed within the last 4 weeks
Overall Survival (OS)	OS will be calculated from the date of treatment initiation to the date of death or last contact	48 months
Response Rate (RR)	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 assessments will be performed every 8 weeks during treatment and at discontinuation, unless it was performed within the last 4 weeks
Tumor Shrinkage	Tumor shrinkage will be computed using waterfall plots	Tumor assessments will be performed every 8 weeks during treatment and at discontinuation, unless it was performed within the last 4 weeks
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.	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	3 years
Quality of Life (QoL) assessment	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	At baseline and every 8 weeks during treatment
Investigation of antiangiogenic factors (FGF, VEGF, VEGFRR)	Changes in serum levels of antiangiogenic factors during treatment and correlation to the outcome of study treatment.	36 months

Collaborators and Investigators

• Sponsor: Hellenic Cooperative Oncology Group
• Investigators: Study Chair: Aristotelis Bamias, MD, PhD, General Peripheral Hospital of Athens "Alexandra", Medical School, University of Athens

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: December 20, 2010
• First Submitted That Met QC Criteria: December 20, 2010
• First Posted (Estimate): December 21, 2010

Study Record Updates

• Last Update Posted (Actual): February 14, 2017
• Last Update Submitted That Met QC Criteria: February 13, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Kidney Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Bevacizumab; Sirolimus
• Other Study ID Numbers: HE 21/10; 2010-020664-38 (EudraCT Number)