Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma

NCT01491672 | Completed Phase 2 Results

• 2 other identifiers: CRAD001L24042010-020447-13
• Study Type: interventional
• Target: 134
• Locations: 6 countries
• Sites: 17

Brief Summary

This study will evaluate everolimus as second-line therapy in patients with metastatic renal cell carcinoma. Each patient will be enrolled and stratified in one of three cohorts based upon their first-line therapy: 1) prior cytokines, 2) prior sunitinib, or 3) prior anti-VEGF therapy other than sunitinib.

Conditions

Metastatic Renal Cell Carcinoma

Keywords

Metastatic Renal Cell Carcinoma; Second Line; Everolimus; RAD001

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) - All Participants

  PFS during second-line treatment was defined as the time from the date of enrollment to the date of the first documented disease progression or death due to any cause. The primary analysis of PFS was based on a local radiology review of CT scans and MRI collected until the participant experienced disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0.

  20 months

Secondary Outcomes (5)

• Duration of PFS for Each First-line Treatment Cohort

  20 months

• Overall Survival (OS)

  28 months

• Clinical Benefit Rate (CBR)

  20 months

• Objective Response Rate (ORR)

  20 months

• Duration of Response (DoR)

  20 months

Study Arms (1)

RAD001

EXPERIMENTAL

Participants, received RAD001 10 mg orally once daily.

Drug: RAD001

Interventions

RAD001 DRUG

Study drug was supplied as 5 mg tablets in blister packs.

Also known as: Everolimus

RAD001

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old.
• Patients with advanced renal cell carcinoma of a histological or cytological confirmation of clear cell (or with a component of clear cell) renal carcinoma that have previously progressed on or were intolerant to first-line therapy with sunitinib, sorafenib, pazopanib, axitinib, bevacizumab, or cytokine therapy.
• Patients must have had prior nephrectomy (partial or total).
• Patients with at least one measurable lesion at baseline as per the RECIST 1.0 criteria. If skin lesions are reported as target lesions, they should be documented (at baseline and at every physical exam) using color photography and a measuring device (such as a caliper) in clear focus to allow the size of the lesion(s) to be determined from the photograph.
• Patients with a Karnofsky Performance Status ≥ 70%.
• Adequate bone marrow function as shown by:
• ANC ≥ 1.5 x 109/L,
• Platelets ≥ 100 x 109/L,
• Hemoglobin \>9 g/dL
• Adequate liver function as shown by:
• Serum bilirubin ≤ 1.5 x ULN,
• ALT and AST ≤ 2.5 x ULN. Patients with known liver metastases may enroll if their AST and ALT ≤ 5 x ULN,
• INR \< 1.3 (INR \< 3 in patients treated with anticoagulants)
• Adequate renal function: serum creatinine ≤ 2.0 x ULN.
• Fasting serum cholesterol ≤300 mg/dl OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN.

You may not qualify if:

• Patients with brain metastases.
• 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 in anticipation of the need for major surgical procedure during the course of the study.
• Patients who had radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed up to 2 weeks prior to study treatment start).
• Patients with a serious non-healing wound, ulcer, or bone fracture.
• Patients with a history of seizure(s) not controlled with standard medical therapy.
• Patients who have received more than one prior treatment regimen for metastatic renalcell carcinoma
• Patients who have received adjuvant therapy for RCC
• Patients who have previously received systemic mTOR inhibitors (eg, sirolimus, temsirolimus, everolimus)
• Patients with a known hypersensitivity to everolimus or other rapamycins (eg, sirolimus, temsirolimus) or to its excipients.
• History or clinical evidence of central nervous system (CNS) metastases.
• Clinically significant gastrointestinal abnormalities including, but not limited to:
• Malabsorption syndrome:
• Major resection of the stomach or small bowel that could affect the absorption of study drug

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (17)

Memorial Sloan Kettering Cancer Center

New York, New York, 90033, United States

Location

Novartis Investigative Site

San Miguel de Tucumán, Tucumán Province, T4000, Argentina

Location

Novartis Investigative Site

Rio Negro, Viedma, 8500, Argentina

Location

Novartis Investigative Site

Florianópolis, Santa Catarina, 88034-000, Brazil

Location

Novartis Investigative Site

Barretos, São Paulo, 14784-400, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01246-000, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01509-900, Brazil

Location

Novartis Investigative Site

Sofia, 1784, Bulgaria

Location

Novartis Investigative Site

Beijing, Beijing Municipality, 100730, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310003, China

Location

Novartis Investigative Site

Beijing, 100021, China

Location

Novartis Investigative Site

Guangzhou, 510060, China

Location

Novartis Investigative Site

Shanghai, 200032, China

Location

Novartis Investigative Site

Leningrad Region, Russia, 188663, Russia

Location

Novartis Investigative Site

Moscow, Russia, 125284, Russia

Location

Novartis Investigative Site

Nizhny Novgorod, Russia, 603001, Russia

Location

Novartis Investigative Site

Obninsk, Russia, 249036, Russia

Location

Related Publications (2)

• Yang L, Alyasova A, Ye D, Ridolfi A, Dezzani L, Motzer RJ. RECORD-4 multicenter phase 2 trial of second-line everolimus in patients with metastatic renal cell carcinoma: Asian versus non-Asian population subanalysis. BMC Cancer. 2018 Feb 17;18(1):195. doi: 10.1186/s12885-018-4091-5.

  PMID: 29454306 DERIVED

• Motzer RJ, Alyasova A, Ye D, Karpenko A, Li H, Alekseev B, Xie L, Kurteva G, Kowalyszyn R, Karyakin O, Neron Y, Cosgriff T, Collins L, Brechenmacher T, Lin C, Morgan L, Yang L. Phase II trial of second-line everolimus in patients with metastatic renal cell carcinoma (RECORD-4). Ann Oncol. 2016 Mar;27(3):441-8. doi: 10.1093/annonc/mdv612. Epub 2015 Dec 17.

  PMID: 26681676 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

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2011
• First Posted: December 14, 2011
• Study Start: November 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 6, 2016
• Results First Posted: June 2, 2016

Record last verified: 2016-06

Locations

US (1); BU (1); RU (4); AR (2); BR (4); CN (5)