A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma (MACS0448)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01206764
First received: September 21, 2010
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Renal Cell Carcinoma
Drug: RAD001
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Evaluate the PFS rate over. [ Time Frame: December 2013 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate the disease control rate (stable disease [SD] + partial response [PR] + complete response [CR]); [ Time Frame: December 2013 ] [ Designated as safety issue: No ]
  • Evaluate the objective response rate (ORR; where ORR = CR + PR) and duration [ Time Frame: December 2013 ] [ Designated as safety issue: No ]
  • Describe the safety profile of RAD001. [ Time Frame: December 2013 ] [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: November 2009
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAD001 Drug: RAD001
Other Name: Everolimus

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01206764

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
Algeria
Novartis Investigative Site Recruiting
Alger, Algeria, 016000
Novartis Investigative Site Recruiting
Oran, Algeria
India
Novartis Investigative Site Completed
Indore, Madhya Pradesh, India, 452 008
Novartis Investigative Site Completed
Pune, Maharashtra, India, 411013
Jordan
Novartis Investigative Site Withdrawn
Amman, Jordan, 11195
Novartis Investigative Site Recruiting
Amman, Jordan
Lebanon
Novartis Investigative Site Recruiting
Beirut, Lebanon
Russian Federation
Novartis Investigative Site Withdrawn
Ulyanovsk, Russia, Russian Federation, 432063
Novartis Investigative Site Withdrawn
Kazan, Tatarstan Republic, Russian Federation, 420029
Novartis Investigative Site Recruiting
Moscow, Russian Federation, 115478
Novartis Investigative Site Withdrawn
Moscow, Russian Federation, 125284
Novartis Investigative Site Recruiting
Samara, Russian Federation, 443031
Saudi Arabia
Novartis Investigative Site Recruiting
Riyadh, Saudi Arabia, 11211
South Africa
Novartis Investigative Site Recruiting
Cape Town, South Africa, 7925
Novartis Investigative Site Recruiting
Cape Town, South Africa, 7500
Novartis Investigative Site Recruiting
Durban, South Africa, 4001
Novartis Investigative Site Recruiting
Parktown, South Africa, 2193
Thailand
Novartis Investigative Site Completed
Bangkok, Thailand, 10400
Novartis Investigative Site Active, not recruiting
Chiang Mai, Thailand, 50200
Novartis Investigative Site Completed
Songkla, Thailand, 90110
Tunisia
Novartis Investigative Site Not yet recruiting
Tunis, Tunisie, Tunisia, 1008
Novartis Investigative Site Recruiting
Ariana, Tunisia, 2080
Novartis Investigative Site Not yet recruiting
Sousse, Tunisia, 4000
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01206764     History of Changes
Other Study ID Numbers: CRAD001LIC01
Study First Received: September 21, 2010
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration
Algeria: Ministry of Health
Egypt: Ministry of Health, Drug Policy and Planning Center
India: Ministry of Health
Jordan: Ethical Committee
Lebanon: Ministry of Public Health
Russia: Ministry of Health of the Russian Federation
Saudi Arabia: Ministry of Health
South Africa: Medicines Control Council
Thailand: Ministry of Public Health
Tunisia: Ministry of Public Health

Keywords provided by Novartis:
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:
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
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 22, 2014