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

NCT01266837 | Completed Phase 4

• 2 other identifiers: CRAD001LDE36T2010-021370-11
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Metastatic Renal Cell Carcinoma; Failure of Exactly One Prior VEGF-targeted Therapy

Keywords

metastatic renal cell carcinoma; biomarker; Everolimus

Outcome Measures

Primary Outcomes (1)

• Rate of patients progression free 6 months after start of study treatment

  2 years after LPI

Secondary Outcomes (1)

• Relation between biomarkers and clinical benefit (response, stable disease and progression/ no clinical benefit) of patients

  2 years after LPI

Study Arms (1)

single arm

OTHER

Treatment with Everolimus

Drug: Everolimus

Interventions

Everolimus DRUG

10 mg p.o once daily

Also known as: Afinitor

single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent
• Aged 18 years and above
• Histologically or cytologically confirmed predominantly clear cell renal cell carcinoma
• Metastatic disease documented by CT or MRI (histological confirmation not mandatory but wishful)
• Patients with or without nephrectomy (partial or total)
• Patients with at least one measurable lesion at baseline according to RECIST criteria 1.1
• Failure of exactly one prior VEGFR-TKI therapy (e.g. sunitinib, sorafenib, pazopanib) for metastatic renal cell carcinoma
• ECOG 0-2
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥75,000/μL
• Absolute neutrophil count ≥1,5x109/l
• Serum creatinine \< 2.5 x ULN
• 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
• Able to swallow the study drug whole as a tablet
• Expected life expectancy of at least 6 months

You may not qualify if:

• Patients who have received \>1 prior VEGFR-TKI therapy or prior therapy with bevacizumab +/- interferon.
• VEGFR-TKI therapy within 14 days prior to start of study drug
• Patients who have previously received systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus).
• Patients with a known hypersensitivity to everolimus or other rapamycin (sirolimus, temsirolimus) or to its excipients.
• Any condition which, in the opinion of the investigator, would preclude participation in this trial
• 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.
• 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.
• Patients in anticipation of the need for major surgical procedure during the course of the study.
• Patients with a serious non-healing wound, ulcer, or bone fracture.
• Patients with a history of seizure(s) not controlled with standard medical therapy.
• 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:
• are asymptomatic and,
• have had no evidence of active CNS metastases for ≥ 3 months prior to enrolment (inactive/controlled CNS metastases are allowed) and,
• have no requirement for steroids or enzyme-inducing anticonvulsants (e.g. carbamazepine, phenobarbital, phenytoin)
• Patients receiving chronic systemic treatment with corticosteroids (dose of \> 10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable.

Sponsors & Collaborators

• iOMEDICO AG: lead
• Novartis: collaborator

Study Sites (8)

Charitè Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Klinik und Poliklinik für Urologie , Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Urologie - Waldkrankenhaus St. Marien

Erlangen, 91054, Germany

Location

Klinik für Innere Medizin (Tumorforschung), Universitätsklinikum Essen

Essen, 45122, Germany

Location

Zentrum Innere Medizin, Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

Klinik für Urologie, Universitätsklinikum Jena

Jena, 07743, Germany

Location

5. Medizinische Klinik, Klinikum Nürnberg

Nuremberg, 90419, Germany

Location

Related Publications (1)

• Staehler M, Stockle M, Christoph DC, Stenzl A, Potthoff K, Grimm MO, Klein D, Harde J, Bruning F, Goebell PJ, Augustin M, Roos F, Benz-Rud I, Marschner N, Grunwald V. Everolimus after failure of one prior VEGF-targeted therapy in metastatic renal cell carcinoma: Final results of the MARC-2 trial. Int J Cancer. 2021 Apr 1;148(7):1685-1694. doi: 10.1002/ijc.33349. Epub 2020 Oct 26.

  PMID: 33070307 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Michael Staehler, Dr. med

  Ludwig-Maximilians-University Munich, Hospital Grosshadern

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2010
• First Posted: December 24, 2010
• Study Start: March 1, 2011
• Primary Completion: September 26, 2017
• Study Completion: October 31, 2017
• Last Updated: November 14, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8)