A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.

NCT01206764 | Completed Phase 4 Results

• 1 other identifier: CRAD001LIC01
• Study Type: interventional
• Target: 143
• Locations: 10 countries
• Sites: 22

Brief Summary

Renal cell carcinoma (RCC) accounts for more than 200,000 new cases of cancer and over 100,000 cancer deaths annually in the World (Ferlay, et al., 2004). It is estimated that there were about 15,000 new cases of RCC in the region that excludes the Americas, European Union and Japan. Renal cell carcinomas arise from the proximal tubal epithelium are more common in males than in females with an overall lifetime risk of 1 in 75 and a median age of diagnosis of 65 years. Everolimus (Certican®) has been approved since 2003 in more than 60 countries for the prevention of organ rejection in patients with renal and cardiac transplantation. Everolimus (RAD001) is a derivative of rapamycin, which acts as a signal transduction inhibitor. It targets mTOR, a key protein kinase regulating cell growth, proliferation, and survival. The mTOR pathway activity is modulated by the phosphatidylinositol-3-kinase (PI3K)/protein kinase B AKT (AKT) pathway, a pathway known to be deregulated in numerous human cancers. RAD001 (Afinitor®) has been investigated as an anticancer agent based on its potential to act:

• directly on the tumor cells by inhibiting tumor cell growth and proliferation;
• indirectly by inhibiting angiogenesis leading to reduced tumor vascularity (via potent inhibition of tumor cell hypoxia-inducible factor 1 (HIF-1) activity, VEGF production, and VEGF-induced proliferation of endothelial cells). Primary: To evaluate the PFS rate over time. Secondary:
• To evaluate the disease control rate (stable disease \[SD\] + partial response \[PR\] + complete response \[CR\]);
• To evaluate the objective response rate (ORR; where ORR = CR + PR) and duration;
• To describe the safety profile of RAD001.

Conditions

Renal Cell Carcinoma

Keywords

RCC,; mTOR pathway,; angiogenesis,; PFS,; partial response [PR] + complete response [CR]); metastatic recurrent renal cell carcinoma; metastatic unresectable renal cell carcinoma

Outcome Measures

Primary Outcomes (1)

• PFS (Progression-Free Survival)

  the time from the date of the start of RAD001 treatment to the date of the first documented disease progression or death due to any cause

  Approximately 4 years

Secondary Outcomes (4)

• Disease Control Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]);

  Approximately 4 years

• Objective Response Rate (ORR; Where ORR = CR + PR)

  Approximately 4 years

• Duration of Response (DOR)

  Approximately 4 years

• Overall Survival

  Approximately 4 years

Study Arms (1)

RAD001

EXPERIMENTAL

Drug: RAD001

Interventions

RAD001 DRUG

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 with confirmed clear or non-clear cell histology, with or without nephrectomy, and with any MSKCC prognosis;
• Prior cytokine therapy is permitted;
• Patients with at least one measurable lesion at baseline as per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. If skin lesions are reported as target lesions, they must 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;
• Life expectancy ≥3 months. Life expectancy should be judged in relation to other determining patient eligibility factors such as laboratory results, Karnofsky Performance Status, etc.;
• Patients with a Karnofsky Performance Status ≥70%;
• Adequate bone marrow function as shown by: absolute neutrophil count (ANC) ≥1.5 x 109/L, platelets ≥100 x 109/L, hemoglobin (Hb) \>9 g/dL;
• Adequate liver function: serum bilirubin ≤1.5 x upper limit of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) ≤2.5 x ULN;
• Adequate renal function: serum creatinine ≤1.5 x ULN;
• Females of childbearing potential must have had a negative serum or urine pregnancy test 7 days prior to the administration of the study treatment start;
• Patients who give a written informed consent obtained according to local guidelines.

You may not qualify if:

• Patients within 2 weeks post-minor surgery (e.g., herniorrhaphy), 4 weeks post-major surgery (e.g., intra-thoracic, intra-abdominal, or intra-pelvic) to avoid wound healing complications. Percutaneous biopsies require no waiting time prior to study entry;
• Patients with a recent history of hemoptysis, ≥0.5 teaspoon of red blood;
• Patients who have received prior systemic treatment for their metastatic RCC other than with cytokine therapy;
• Patients who received prior therapy with a VEGF pathway inhibitor, such as sunitinib, sorafenib, and bevacizumab;
• Patients who have previously received mTOR inhibitors (sirolimus, temsirolimus, everolimus, deferolimus);
• History or clinical evidence of central nervous system (CNS) metastases. Note: 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; Have had no evidence of active CNS metastases for ≥6 months prior to enrollment and; Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC);
• 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; Active peptic ulcer disease; Inflammatory bowel disease; Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation; History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning of study treatment;
• Patients receiving chronic systemic treatment with corticosteroids (dose of ≥10 mg/day methylprednisone equivalent) or another immune-suppressive agent. Inhaled and topical steroids are acceptable, as well as opotherapy after bilateral adrenal gland removal;
• Patients with a known history of human immunodeficiency virus seropositivity;
• Patients with autoimmune hepatitis;
• Patients with an active, bleeding diathesis. Patients may use coumadin or heparin preparations;
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study;
• Patients who have a history of another primary malignancy ≤3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of uterine;
• Female patients who are pregnant or breastfeeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the study by both sexes. Oral contraceptives are not acceptable;

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (22)

Novartis Investigative Site

Algiers, 016000, Algeria

Location

Novartis Investigative Site

Oran, Algeria

Location

Novartis Investigative Site

Al Mansurah, Egypt

Location

Novartis Investigative Site

Alexandria, 21131, Egypt

Location

Novartis Investigative Site

Cairo, Egypt

Location

Novartis Investigative Site

Indore, Madhya Pradesh, 452 008, India

Location

Novartis Investigative Site

Pune, Maharashtra, 411013, India

Location

Novartis Investigative Site

Amman, 11941, Jordan

Location

Novartis Investigative Site

El Achrafiyé, 166830, Lebanon

Location

Novartis Investigative Site

Moscow, 115478, Russia

Location

Novartis Investigative Site

Samara, 443031, Russia

Location

Novartis Investigative Site

Riyadh, 11211, Saudi Arabia

Location

Novartis Investigative Site

Cape Town, 7500, South Africa

Location

Novartis Investigative Site

Cape Town, 7925, South Africa

Location

Novartis Investigative Site

Durban, 4001, South Africa

Location

Novartis Investigative Site

Parktown, 2193, South Africa

Location

Novartis Investigative Site

Songkhla, Hat Yai, 90110, Thailand

Location

Novartis Investigative Site

Bangkok, 10400, Thailand

Location

Novartis Investigative Site

Chiang Mai, 50200, Thailand

Location

Novartis Investigative Site

Tunis, Tunisie, 1007, Tunisia

Location

Novartis Investigative Site

Aryanah, 2080, Tunisia

Location

Novartis Investigative Site

Sousse, 4000, Tunisia

Location

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 Pharmaceuticals

Novartis.email@novartis.com

8627788300

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 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: September 22, 2010
• Study Start: November 11, 2009
• Primary Completion: June 6, 2017
• Study Completion: July 1, 2017
• Last Updated: June 24, 2019
• Results First Posted: June 24, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

SA (1); ZA (4); TH (3); IN (2); RU (2); AL (2); LE (1); JO (1); EG (3); TU (3)