An Open Label, Single Arm Trial to Characterize Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus After Failure of the First VEGF-targeted Therapy (MARC-2)

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IVBiomarker/Laboratory analysis, TreatmentActive18 and overOtherCRAD001LDE36T
2010-021370-11, NCT01266837

Trial Description

Summary

A single arm, open-label, multi-center phase IV clinical trial for patients with metastatic renal cell carcinoma, who have progressed on or after the first VEGF-targeted therapy.

Eligibility Criteria

Inclusion Criteria:

1. Provide written informed consent

2. Aged 18 years and above

3. Histologically or cytologically confirmed predominantly clear cell renal cell carcinoma

4. Metastatic disease documented by CT or MRI (histological confirmation not mandatory but wishful)

5. Patients with or without nephrectomy (partial or total)

6. Patients with at least one measurable lesion at baseline according to RECIST criteria 1.1

7. Failure of exactly one prior VEGFR-TKI therapy (e.g. sunitinib, sorafenib, pazopanib) for metastatic renal cell carcinoma

8. ECOG 0-2

9. Hemoglobin ≥ 9.0 g/dL

10. Platelet count ≥75,000/μL

11. Absolute neutrophil count ≥1,5x109/l

12. Serum creatinine < 2.5 x ULN

13. Liver function: Serum bilirubin ≤ 1.5 x ULN, AST or ALT ≤ 2.5 x ULN. Patients with suspected liver metastasis: AST and ALT ≤ 5x ULN

14. Able to swallow the study drug whole as a tablet

15. Expected life expectancy of at least 6 months

16. Women of childbearing potential must have had a negative serum pregnancy test within 14 days prior to the administration of the study treatment or must have a documented condition that prohibits pregnancy (e.g. hysterectomy, post-menopausal).

Exclusion Criteria:

1. Patients who have received >1 prior VEGFR-TKI therapy or prior therapy with bevacizumab +/- interferon.

2. VEGFR-TKI therapy within 14 days prior to start of study drug

3. Patients who have previously received systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus).

4. Patients with a known hypersensitivity to everolimus or other rapamycin (sirolimus, temsirolimus) or to its excipients.

5. Any condition which, in the opinion of the investigator, would preclude participation in this trial

6. Patients within 4 weeks post-major surgery (e.g., intra-thoracic, intra-abdominal or intrapelvic), open biopsy, or significant traumatic injury to avoid wound healing complications. Minor procedures and percutaneous biopsies or placement of vascular access device require 7 days prior to study entry.

7. Patients who had radiation therapy within 4 weeks prior to start of study treatment. Palliative radiotherapy to bone lesions within 2 weeks prior to study treatment start.

8. Patients in anticipation of the need for major surgical procedure during the course of the study.

9. Patients with a serious non-healing wound, ulcer, or bone fracture.

10. Patients with a history of seizure(s) not controlled with standard medical therapy.

11. History or clinical evidence of central nervous system (CNS) metastases. Subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:

1. are asymptomatic and,

2. have had no evidence of active CNS metastases for ≥ 3 months prior to enrolment (inactive/controlled CNS metastases are allowed) and,

3. have no requirement for steroids or enzyme-inducing anticonvulsants (e.g. carbamazepine, phenobarbital, phenytoin)

12. Patients receiving chronic systemic treatment with corticosteroids (dose of > 10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable.

13. Poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN.

14. Impaired liver function classified as Child-Pugh class C.

15. Active (acute or chronic) or uncontrolled infection of bacterial, mycotic or viral genesis.

16. Liver disease such as chronic active hepatitis or chronic persistent hepatitis.

17. Patients with a known history of HIV seropositivity.

18. Patients with active bleeding disorders.

19. Patients who have any severe and/or uncontrolled medical conditions or other conditions within the past 12 months that could affect their participation in the study such as cardiac angioplasty or stenting, unstable angina pectoris, symptomatic peripheral vascular disease, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, any disorders that impair the ability to evaluate the patient or for the patient to complete the study.

20. Patients who have a history of another primary malignancy and off treatment for ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix or breast, and localized cancer of the bladder (T1) and prostate (T1 - T2).

21. Female patients who are pregnant or breast feeding.

22. Men and women of reproductive potential who are not using highly effective birth control methods. Oral contraceptives for female patients and barrier contraceptives are not acceptable. For definition of highly effective birth control methods please refer to section 12.3.6 of this protocol.

23. Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start.

24. Patients unwilling or unable to comply with the protocol.

25. Exclusion criteria for MRI: intracorporal metal (e.g. incompatible heart valves, pacemakers), contrast media allergy, claustrophobia

Trial Contact Information

Trial Lead Organizations/Sponsors

iOMEDICO AG

  • Novartis Pharmaceuticals Corporation
Michael Staehler, Study Director
Luise Strassl
Ph: +49 (0)761 15242 Ext.75
Email: luise.strassl@iomedico.com

Trial Sites

Germany

Berlin

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

Volker Solomon
Ph: 0049(0)3084452742

Dresden

Universitatsklinikum Carl Gustav Carus

Xenia Lueck
Ph: 0049(0)3514584425

Erlangen

Waldkrankenhaus St. Marien gGmbH

Ruth Schaffer-Ziegelitz
Ph: 0049(0)91318223498

Essen

Universitaetsklinikum Essen

Diana Cortes-Incio
Ph: 0049(0)2017233155

Hannover

Medizinische Hochschule Hannover

Cordula Heise
Ph: 0049(0)5115324077

Homburg

Universitaetsklinikum des Saarlandes

Ursula Kayser
Ph: 0049(0)68411624787

Jena

Klinikum der Friedrich-Schiller Universitaet Jena

Katharina Schaarschmidt
Ph: 0049(0)3641935264

Nürnberg

5. Medizinische Klinik, Klinikum Nürnberg

Karin Westphal
Ph: 0049(0)9113983085

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01266837
ClinicalTrials.gov processed this data on April 09, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.