RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed After Treatment With Sorafenib and/or Sunitinib

NCT00410124 | Completed Phase 3 Results

• 2 other identifiers: CRAD001C22402006-002070-21
• Study Type: interventional
• Target: 416
• Locations: 10 countries
• Sites: 93

Brief Summary

To assess whether daily treatment with RAD001 could slow the growth and spread of metastatic carcinoma of the kidney. The safety of RAD001 was also to be studied in this trial.

Conditions

Metastatic Renal Cell Carcinoma

Keywords

advanced kidney cancer; everolimus; kidney cancer; oral therapy

Outcome Measures

Primary Outcomes (1)

• Progressive Free Survival (PFS) in Patients Who Receive RAD001 Plus Best Supportive Care(BSC) Versus Patients Who Receive Matching Placebo Plus BSC

  Progression Free survival is defined as the time from randomization to the date of first documented disease progression or death from any cause. The primary statistical analysis of PFS was based on central radiological assessments using a one-sided stratified log-rank test. Radiological assessments: every 8 weeks (+/-1 week) during the first year and every 12 weeks (+/- 1 week) during the second year and thereafter and at the end of the study. Kaplan-Meier methodology was used to estimate the median PFS for each treatment group.

  Time from randomization to dates of disease progression, death from any cause or last tumor assessment reported between date of first patient randomized until 28Feb2008 cut of date.

Secondary Outcomes (12)

• Overall Survival (OS) Assessed by the Monthly Overall Survival Assessments

  Assessed every month up to 2 years after the last patient was randomized into the study from the date of randomization to the time of death. (Data cutoff was 15Nov2009)

• Best Overall Response Rate in Patients Who Receive RAD001 Plus BSC Versus Matching Placebo Plus BSC

  Time from randomization to dates of disease progression, death from any cause or last tumor assessment reported, between date of first patient randomized until 28Feb2008 cutoff date

• Duration of Response in Patients Who Receive RAD001 Plus BSC Versus Placebo Plus BSC

  Time from randomization to dates of disease progression, death from any cause or last tumor assessment reported, between date of first patient randomized until 28Feb2008 cutoff date

• Analysis of Time to Definitive Deterioration of the Global Health Status/QoL Scale(QL) Scores of the EORTC QLQ-30 Questionnaire by at Least 10 Percent Using Kaplan Meier Method, by Treatment.

  Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date

• Time to Definitive Deterioration of the FKS-DRS Risk Score by at Least 2 Score Units Using Kaplan-Meier Method, by Treatment.

  Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date

Study Arms (2)

RAD001 +BSC

EXPERIMENTAL

The study drugs were self administered by the patients. Patients were instructed to take the study drug as specified in the protocol. Patients were instructed to take two tablets (5 mg each) by mouth every day. Tablets were to be taken one tablet after another with a glass of water, at the same time each day in a fasting state or with a light fat-free meal. If disease progression occurred, patients were unblinded and if they were receiving RAD001, they would discontinue the study. Otherwise, they would be given the option to continue in the extension open label phase of 2 tablets of RAD001 5mg by mouth every day.

Drug: RAD001

Placebo (plus BSC)

PLACEBO COMPARATOR

Patients received matching placebo of RAD001 tablets twice a day along with Best Supportive Care. With the documented disease progression, the investigator could unblind the patient. If unblinded patient was receiving placebo treatment, they were given the option to continue in the extension open label phase of 2 tablets of RAD001 5mg by mouth every day.

Drug: Placebo

Interventions

RAD001 DRUG

The dose of RAD001 was 10 mg/day. Patients were instructed to take two tablets (5 mg each) by mouth every day.

Also known as: Everolimus

RAD001 +BSC

Placebo DRUG

Placebo (plus BSC)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with metastatic carcinoma and with histological or cytological confirmation of clear cell RCC (tissue from the original diagnosis of renal cell cancer is acceptable).
• The date of progression on sunitinib and/or sorafenib must be within 6 months.
• Patients may have received one or both agents
• Prior therapy with cytokines (i.e., IL-2, Interferon) and/or VEGF-ligand inhibitors (i.e., bevacizumab) are permitted.
• Prior vaccine therapy in the adjuvant setting is permitted.
• Patients with at least one measurable lesion at baseline as per the Response evaluation criteria in solid tumors (RECIST) criteria, either on physical exam or as determined by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI).
• Patients with a Karnofsky Performance Status ≥70%.
• Adequate bone marrow, liver and renal function.
• Patients with a life expectancy ≥ 3 months.
• Women of childbearing potential must have had a negative serum or urine pregnancy test 48 hours prior to the administration of the first study treatment.
• Patients who give a written informed consent obtained according to local guidelines

You may not qualify if:

• Patients currently receiving chemotherapy, immunotherapy, or radio-therapy or who have received these within 4 weeks of study entry
• Patients who have previously received mTOR inhibitors.
• Patients with a known hypersensitivity to RAD001 or other rapamycins (sirolimus, temsirolimus) or to its excipients.
• Patients with untreated CNS metastases or who are neurologically unstable despite treatment of the CNS metastases. (Patients with treated CNS metastases, who are neurologically stable off of corticosteroids, are eligible to enter study).
• Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent
• Patients with a known history of HIV seropositivity.
• Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin)
• Patients who have any severe and/or uncontrolled medical conditions
• 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 cervix
• Female patients who are pregnant or breast feeding, 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 trial by both sexes.
• Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to randomization
• Patients unwilling to or unable to comply with the protocol

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (93)

Novartis Investigative Site

Fayetteville, Arkansas, 72703, United States

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Novartis Investigative Site

Duarte, California, 91010-3000, United States

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Sacramento, California, 95817, United States

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San Francisco, California, 94115, United States

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Novartis Investigative Site

Santa Monica, California, 90404, United States

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Novartis Investigative Site

Ocoee, Florida, *see dep*, United States

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Novartis Investigative Site

Orlando, Florida, 32806, United States

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Novartis Investigative Site

Indianapolis, Indiana, 46202, United States

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Novartis Investigative Site

Indianapolis, Indiana, 46227, United States

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Louisville, Kentucky, 40202, United States

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Baltimore, Maryland, 21201, United States

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Detroit, Michigan, 48201, United States

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Minneapolis, Minnesota, 55455, United States

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Columbia, Missouri, 65201, United States

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St Louis, Missouri, 63110, United States

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Las Vegas, Nevada, 89135, United States

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Buffalo, New York, 14263, United States

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New York, New York, 10021, United States

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Chapel Hill, North Carolina, 27599, United States

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Durham, North Carolina, 27710, United States

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Raleigh, North Carolina, 27609, United States

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Canton, Ohio, 44718, United States

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Portland, Oregon, 97210, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Bedford, Texas, 76022, United States

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Dallas, Texas, 75246, United States

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San Antonio, Texas, 78229, United States

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Tyler, Texas, 75702, United States

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Seattle, Washington, 98109-1023, United States

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Spokane, Washington, 99202, United States

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Morgantown, West Virginia, 26506, United States

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Camperdown, New South Wales, 2050, Australia

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Randwick, New South Wales, 2031, Australia

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Westmead, New South Wales, 2145, Australia

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South Brisbane, Queensland, 4101, Australia

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Woodville, South Australia, 5011, Australia

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Heidelberg, Victoria, 3084, Australia

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Edmonton, Alberta, T6G 1Z2, Canada

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Vancouver, Alberta, V5Z 4E6, Canada

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Hamilton, Ontario, L8V 5C2, Canada

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London, Ontario, N6A 4G5, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H3G 1A4, Canada

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Bordeaux, 33075, France

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Lille, 59020, France

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Lyon, 69373, France

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Paris, 75015, France

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Saint-Herblain Cédex, 44805, France

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Strasbourg, 67091, France

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Toulouse, 31052, France

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Novartis Investigative Site

Villejuif, 94805, France

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Dresden, 01307, Germany

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Frankfurt/M, 60590, Germany

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Hanover, 30625, Germany

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Kassel, 34125, Germany

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Mainz, 55101, Germany

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Novartis Investigative Site

München, 81675, Germany

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Novartis Investigative Site

Cremona, CR, 26100, Italy

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Genova, GE, 16132, Italy

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Milan, MI, 20133, Italy

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Modena, MO, 41100, Italy

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Perugia, PG, 06129, Italy

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Pavia, PV, 27100, Italy

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Roma, RM, 00152, Italy

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Napoli, 80132, Italy

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Akita, Akita, 010-8543, Japan

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Chiba, Chiba, 260-8717, Japan

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Matsuyama, Ehime, 791-0280, Japan

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Fukuoka, Fukuoka, 812-8582, Japan

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Sapporo, Hokkaido, 060-8543, Japan

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Sapporo, Hokkaido, 060-8648, Japan

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Tsukuba, Ibaraki, 305-8576, Japan

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Kurashiki, Okayama-ken, 710-8602, Japan

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Osaka, Osaka, 537-8511, Japan

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Sayama, Osaka, 589-8511, Japan

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Sunto-gun, Shizuoka, 411-8777, Japan

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Utsunomiya, Tochigi, 320-0834, Japan

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Novartis Investigative Site

Tokushima, Tokushima, 770-8503, Japan

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Chuo-ku, Tokyo, 104-0045, Japan

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Novartis Investigative Site

Utrecht, Netherlands, 3584CX, Netherlands

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Amsterdam, Netherlands

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Leiden, 2300 RC, Netherlands

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Novartis Investigative Site

Nijmegen, 6525 GA, Netherlands

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Novartis Investigative Site

Gdañsk, 80-219, Poland

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Novartis Investigative Site

Lodz, 90-153, Poland

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Novartis Investigative Site

Warsaw, 00-909, Poland

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Novartis Investigative Site

Wroclaw, 50-367, Poland

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Novartis Investigative Site

Barcelona, Barcelona, 08035, Spain

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Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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Novartis Investigative Site

Barcelona, Spain, 08025, Spain

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Novartis Investigative Site

Madrid, 28041, Spain

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Novartis Investigative Site

Valencia, 46009, Spain

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Related Publications (7)

• Stein A, Bellmunt J, Escudier B, Kim D, Stergiopoulos SG, Mietlowski W, Motzer RJ; RECORD-1 Trial Study Group. Survival prediction in everolimus-treated patients with metastatic renal cell carcinoma incorporating tumor burden response in the RECORD-1 trial. Eur Urol. 2013 Dec;64(6):994-1002. doi: 10.1016/j.eururo.2012.11.032. Epub 2012 Nov 21.

  PMID: 23219086 DERIVED

• Stein A, Wang W, Carter AA, Chiparus O, Hollaender N, Kim H, Motzer RJ, Sarr C. Dynamic tumor modeling of the dose-response relationship for everolimus in metastatic renal cell carcinoma using data from the phase 3 RECORD-1 trial. BMC Cancer. 2012 Jul 23;12:311. doi: 10.1186/1471-2407-12-311.

  PMID: 22824201 DERIVED

• Oudard S, Thiam R, Fournier LS, Medioni J, Lamuraglia M, Scotte F, Fabre E, Kim D, Kpamegan E, Panneerselvam A, Cuenod CA. Optimisation of the tumour response threshold in patients treated with everolimus for metastatic renal cell carcinoma: analysis of response and progression-free survival in the RECORD-1 study. Eur J Cancer. 2012 Jul;48(10):1512-8. doi: 10.1016/j.ejca.2012.01.027. Epub 2012 Feb 16.

  PMID: 22342553 DERIVED

• Porta C, Calvo E, Climent MA, Vaishampayan U, Osanto S, Ravaud A, Bracarda S, Hutson TE, Escudier B, Grunwald V, Kim D, Panneerselvam A, Anak O, Motzer RJ. Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial. Eur Urol. 2012 Apr;61(4):826-33. doi: 10.1016/j.eururo.2011.12.057. Epub 2012 Jan 5.

  PMID: 22297244 DERIVED

• Calvo E, Escudier B, Motzer RJ, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Ravaud A, Kim D, Panneerselvam A, Anak O, Figlin RA. Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer. 2012 Feb;48(3):333-9. doi: 10.1016/j.ejca.2011.11.027. Epub 2011 Dec 30.

  PMID: 22209391 DERIVED

• White DA, Camus P, Endo M, Escudier B, Calvo E, Akaza H, Uemura H, Kpamegan E, Kay A, Robson M, Ravaud A, Motzer RJ. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med. 2010 Aug 1;182(3):396-403. doi: 10.1164/rccm.200911-1720OC. Epub 2010 Mar 1.

  PMID: 20194812 DERIVED

• Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. doi: 10.1016/S0140-6736(08)61039-9. Epub 2008 Jul 22.

  PMID: 18653228 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; 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: Novartis Pharmaceuticals
• Organization: Novartis Pharmaceuticals

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2006
• First Posted: December 12, 2006
• Study Start: November 1, 2006
• Primary Completion: February 1, 2008
• Study Completion: October 1, 2011
• Last Updated: January 15, 2013
• Results First Posted: January 15, 2013

Record last verified: 2012-12

Locations

JP (14); US (31); IT (8); CA (7); NL (4); ES (5); PL (4); AU (6); FR (8); DE (6)