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

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ClinicalTrials.gov Identifier: NCT01206764
Recruitment Status : Completed
First Posted : September 22, 2010
Results First Posted : June 24, 2019
Last Update Posted : June 24, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Renal Cell Carcinoma Drug: RAD001 Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 143 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center Phase 2 Study to Evaluate Everolimus as Monotherapy Treatment for Patients With Metastatic Recurrent and/or Unresectable Renal Cell Carcinoma (EVERMORE).
Actual Study Start Date : November 11, 2009
Actual Primary Completion Date : June 6, 2017
Actual Study Completion Date : July 1, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: RAD001 Drug: RAD001
Other Name: Everolimus




Primary Outcome Measures :
  1. PFS (Progression-Free Survival) [ Time Frame: Approximately 4 years ]
    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


Secondary Outcome Measures :
  1. Disease Control Rate (Stable Disease [SD] + Partial Response [PR] + Complete Response [CR]); [ Time Frame: Approximately 4 years ]
    The disease control rate was based on the data as per local radiological review following the RECIST criteria. The disease control rate is defined as the proportion of patients with CR, PR, or SD and was summarized in terms of percentage with 95% exact Clopper-Pearson CIs

  2. Objective Response Rate (ORR; Where ORR = CR + PR) [ Time Frame: Approximately 4 years ]
    The overall tumor response was based on the data as per local radiological review, following RECIST criteria. The ORR is defined as the proportion of patients with CR or PR and was summarized in terms of percentage with 95% exact Clopper-Pearson CIs

  3. Duration of Response (DOR) [ Time Frame: Approximately 4 years ]
    The DOR analysis applied only to patients whose overall response was CR or PR and was defined as the time from onset of response (CR/PR) to progression or death from any cause

  4. Overall Survival [ Time Frame: Approximately 4 years ]
    Overall survival is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Patients may be entered in the study only if they meet all of the following criteria:

  • 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.

Exclusion Criteria:Patients may not be entered into the study if they meet any of the following criteria:

  • 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;
  • Patients who are using other investigational agents or who had received investigational drugs ≤4 weeks prior to study treatment start; Patients unwilling or unable to comply with the protocol.

Other protocol-defined inclusion/exclusion may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01206764


Locations
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Algeria
Novartis Investigative Site
Alger, Algeria, 016000
Novartis Investigative Site
Oran, Algeria
Egypt
Novartis Investigative Site
Alexandria, Egypt, 21131
Novartis Investigative Site
Cairo, Egypt
Novartis Investigative Site
Mansoura, Egypt
India
Novartis Investigative Site
Indore, Madhya Pradesh, India, 452 008
Novartis Investigative Site
Pune, Maharashtra, India, 411013
Jordan
Novartis Investigative Site
Amman, Jordan, 11941
Lebanon
Novartis Investigative Site
Ashrafieh, Lebanon, 166830
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation, 115478
Novartis Investigative Site
Samara, Russian Federation, 443031
Saudi Arabia
Novartis Investigative Site
Riyadh, Saudi Arabia, 11211
South Africa
Novartis Investigative Site
Cape Town, South Africa, 7500
Novartis Investigative Site
Cape Town, South Africa, 7925
Novartis Investigative Site
Durban, South Africa, 4001
Novartis Investigative Site
Parktown, South Africa, 2193
Thailand
Novartis Investigative Site
Songkhla, Hat Yai, Thailand, 90110
Novartis Investigative Site
Bangkok, Thailand, 10400
Novartis Investigative Site
Chiang Mai, Thailand, 50200
Tunisia
Novartis Investigative Site
Tunis, Tunisie, Tunisia, 1007
Novartis Investigative Site
Ariana, Tunisia, 2080
Novartis Investigative Site
Sousse, Tunisia, 4000
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] September 22, 2017
Study Protocol  [PDF] May 12, 2010


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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01206764     History of Changes
Other Study ID Numbers: CRAD001LIC01
First Posted: September 22, 2010    Key Record Dates
Results First Posted: June 24, 2019
Last Update Posted: June 24, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
RCC,
mTOR pathway,
angiogenesis,
PFS,
partial response [PR] + complete response [CR])
metastatic recurrent renal cell carcinoma
metastatic unresectable renal cell carcinoma

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents