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Advanced Gastric CancerPhase 3GRANITE-1NCT00879333

Safety and Efficacy of RAD001 (Everolimus) Monotherapy Plus Best Supportive Care in Patients With Advanced Gastric Cancer (AGC)

A Phase 3 study testing Everolimus in people with Advanced Gastric Cancer, run by Novartis Pharmaceuticals at 122 sites in 22 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study is designed to assess the safety and efficacy of RAD001 monotherapy in patients with advanced gastric cancer which has progressed after one or two lines of prior chemotherapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Gastric Cancer
What is being tested?
Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
656 participants
Where
122 sitesin 22 countries
Study dates
Jul 2009to Jan 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients > 18 years old
  • Histologically or cytologically confirmed and documented gastric adenocarcinoma
  • Documented progression after 1 or 2 prior chemotherapy treatments for advanced disease
  • ECOG Performance Status of < 2
  • Lab parameters within specifically defined intervals
  • Able to provide written informed consent

Who cannot join

  • Patients who have received > 2 prior systemic therapies for advanced disease
  • Administration of another anticancer therapy within 3 weeks prior to randomization
  • Chronic treatment with steroids or another immunosuppressive agent
  • Major surgery within 2 weeks prior to randomization
  • Patients with CNS metastases
  • Any other severe and/or uncontrolled medical condition
  • Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

122 sites in 22 countries.

122 sites in 22 countries

France15 sites
  • Novartis Investigative Site

    Avignon, 84082

  • Novartis Investigative Site

    Clermont-Ferrand, 63003

  • Novartis Investigative Site

    Clichy, 92110

  • Novartis Investigative Site

    Dijon, 21079

  • Novartis Investigative Site

    Lyon, 69373

  • Novartis Investigative Site

    Marseille, 13385

  • Novartis Investigative Site

    Montpellier, 34298

  • Novartis Investigative Site

    Nice, 06189

  • Novartis Investigative Site

    Paris, 75015

  • Novartis Investigative Site

    Pessac, 33604

  • Novartis Investigative Site

    Poitiers, France, 86000

  • Novartis Investigative Site

    Reims, 51092

  • Novartis Investigative Site

    Rennes, 35062

  • Novartis Investigative Site

    Toulouse, 31054

  • Novartis Investigative Site

    Villejuif, 94805

Other trials in France

China14 sites
  • Novartis Investigative Site

    Beijing, 100036

  • Novartis Investigative Site

    Beijing, 100039

  • Novartis Investigative Site

    Chengdu, Sichuan, 610041

  • Novartis Investigative Site

    Guangzhou, Guangdong, 510515

  • Novartis Investigative Site

    Guangzhou, 510060

  • Novartis Investigative Site

    Hangzhou, Zhejiang, 310016

  • Novartis Investigative Site

    Harbin, Heilongjiang, 150081

  • Novartis Investigative Site

    Nanjing, Jiangsu, 210002

  • Novartis Investigative Site

    Shanghai, 200003

  • Novartis Investigative Site

    Shanghai, 200025

  • Novartis Investigative Site

    Shanghai, 200032

  • Novartis Investigative Site

    Shenyang, Liaoning

  • Novartis Investigative Site

    Shijiazhuang, Hebei, 050011

  • Novartis Investigative Site

    Suzhou, Jiangsu, 215006

Other trials in China

Japan14 sites
  • Novartis Investigative Site

    Chuo-ku, Tokyo, 104-0045

  • Novartis Investigative Site

    Fukuoka, Fukuoka, 812-8582

  • Novartis Investigative Site

    Kashiwa, Chiba, 277-8577

  • Novartis Investigative Site

    Kitaadachi-gun, Saitama, 362-0806

  • Novartis Investigative Site

    Koto, Tokyo, 135-8550

  • Novartis Investigative Site

    Matsuyama, Ehime, 791-0280

  • Novartis Investigative Site

    Mitaka, Tokyo, 181-8611

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 464-8681

  • Novartis Investigative Site

    Sagamihara, Kanagawa, 252-0380

  • Novartis Investigative Site

    Sapporo, Hokkaido, 060-8648

  • Novartis Investigative Site

    Sayama, Osaka, 589-8511

  • Novartis Investigative Site

    Sendai, Miyagi, 980-8574

  • Novartis Investigative Site

    Takatsuki, Osaka, 569-8686

  • Novartis Investigative Site

    Utsunomiya, Tochigi, 320-0834

Other trials in Japan

Australia9 sites
  • Novartis Investigative Site

    Box Hill, Victoria, 3128

  • Novartis Investigative Site

    Canberra, Australian Capital Territory, 2605

  • Novartis Investigative Site

    Clayton, Victoria, 3168

  • Novartis Investigative Site

    Footscray, Victoria, 3011

  • Novartis Investigative Site

    Heidelberg, Victoria, 3084

  • Novartis Investigative Site

    Herston, Queensland, 4029

  • Novartis Investigative Site

    Kurralta Park, South Australia, 5037

  • Novartis Investigative Site

    North Adelaide, South Australia, 5006

  • Novartis Investigative Site

    Prahran, Victoria, 3181

Other trials in Australia

United States8 sites
  • University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(4)

    Dallas, Texas, 75390-8527

  • Henry Ford Hospital Dept. of Henry Ford Hospital

    Detroit, Michigan, 48202-2689

  • Highlands Oncology Group DeptofHighlandsOncologyGrp(2)

    Fayetteville, Arkansas, 72703

  • The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)

    Fort Worth, Texas, 76104

  • University of Texas/MD Anderson Cancer Center Gastrointestinal Med. Oncology

    Houston, Texas, 77030-4009

  • University of Minnesota Cancer Center

    Minneapolis, Minnesota, 55455

  • Loma Linda Oncology Medical Group Loma Linda

    Redlands, California, 92374

  • University of Washington Cancer Care Seattle Cancer Alliance

    Seattle, Washington, 98109-1023

Other trials in United States

Germany8 sites
  • Novartis Investigative Site

    Berlin, 13353

  • Novartis Investigative Site

    Bielefeld, 33604

  • Novartis Investigative Site

    Frankfurt, 60488

  • Novartis Investigative Site

    Mainz, Germany, 55131

  • Novartis Investigative Site

    Mannheim, Baden-Wurttemberg, 68305

  • Novartis Investigative Site

    München, 81675

  • Novartis Investigative Site

    Offenburg, 77652

  • Novartis Investigative Site

    Trier, 54290

Other trials in Germany

South Korea7 sites
  • Novartis Investigative Site

    Jeonju, Jeollabuk-do, 561-712

  • Novartis Investigative Site

    Seoul, Korea, 03722

  • Novartis Investigative Site

    Seoul, Korea, 05505

  • Novartis Investigative Site

    Seoul, Korea, 06351

  • Novartis Investigative Site

    Seoul, Korea, 110 744

  • Novartis Investigative Site

    Seoul, 136-705

  • Novartis Investigative Site

    Taegu, 700 - 721

Other trials in South Korea

United Kingdom7 sites
  • Novartis Investigative Site

    East Yorkshire, HU16 5JQ

  • Novartis Investigative Site

    London, SW3 6JJ

  • Novartis Investigative Site

    London, WC1E 6HX

  • Novartis Investigative Site

    Manchester, M20 4BX

  • Novartis Investigative Site

    Northwood, Middlesex, HA6 2RN

  • Novartis Investigative Site

    Sutton, Surrey, SM2 5PT

  • Novartis Investigative Site

    Wolverhampton, WV10 0QP

Other trials in United Kingdom

Canada6 sites
  • Novartis Investigative Site

    Montreal, Quebec, H3G 1A4

  • Novartis Investigative Site

    North Vancouver, British Columbia, V7L 2L7

  • Novartis Investigative Site

    Sherbrooke, Quebec, J1H 5N4

  • Novartis Investigative Site

    Toronto, Ontario, M4N 3M5

  • Novartis Investigative Site

    Toronto, Ontario, M5B 1W8

  • Novartis Investigative Site

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Italy5 sites
  • Novartis Investigative Site

    Aviano, PN, 33081

  • Novartis Investigative Site

    Florence, FI, 50134

  • Novartis Investigative Site

    Frattamaggiore, 80020

  • Novartis Investigative Site

    Modena, MO, 41100

  • Novartis Investigative Site

    Rozzano, MI, 20089

Other trials in Italy

Taiwan5 sites
  • Novartis Investigative Site

    Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, 33305

  • Novartis Investigative Site

    Liouying Township

  • Novartis Investigative Site

    Niaosong Township, Taiwan, 83301

  • Novartis Investigative Site

    Taipei, Taiwan, 10048

  • Novartis Investigative Site

    Taipei

Other trials in Taiwan

Belgium4 sites
  • Novartis Investigative Site

    Charleroi, 6000

  • Novartis Investigative Site

    Ghent, 9000

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Liège, 4000

Other trials in Belgium

Israel4 sites
  • Novartis Investigative Site

    Jerusalem, 9112001

  • Novartis Investigative Site

    Petah Tikva, 49100

  • Novartis Investigative Site

    Ramat Gan, 5266202

  • Novartis Investigative Site

    Rehovot, 76100

Other trials in Israel

Argentina3 sites
  • Novartis Investigative Site

    Buenos Aires, Buenos Aires, C1264AAA

  • Novartis Investigative Site

    Córdoba, Córdoba Province, X5000IUG

  • Novartis Investigative Site

    Rio Negro, Viedma, 8500

Other trials in Argentina

Thailand3 sites
  • Novartis Investigative Site

    Bangkok, 10400

  • Novartis Investigative Site

    Bangkok, 10700

  • Novartis Investigative Site

    Songkhla, 90110

Other trials in Thailand

Mexico2 sites
  • Novartis Investigative Site

    León, Guanajuato, 37000

  • Novartis Investigative Site

    Mexico City, Mexico City, 14080

Other trials in Mexico

Peru2 sites
  • Novartis Investigative Site

    San Borja, Lima region, 41

  • Novartis Investigative Site

    San Isidro, Lima region, 27

Other trials in Peru

Russia2 sites
  • Novartis Investigative Site

    Moscow, 115478

  • Novartis Investigative Site

    Saint Petersburg, 197758

Other trials in Russia

Hong Kong1 site
  • Novartis Investigative Site

    Hong Kong SAR

Other trials in Hong Kong

Netherlands1 site
  • Novartis Investigative Site

    Amsterdam, 1105 AZ

Other trials in Netherlands

New Zealand1 site
  • Novartis Investigative Site

    Auckland

Other trials in New Zealand

Spain1 site
  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

Other trials in Spain

About this study

Official title: A Randomized, Double-blind, Multi-center Phase III Study Comparing Everolimus (RAD001) Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Patients With Advanced Gastric Cancer After Progression on 1 or 2 Prior Systemic Chemotherapy

This study is designed to assess the safety and efficacy of RAD001 monotherapy in patients with advanced gastric cancer which has progressed after one or two lines of prior chemotherapy.

Being tested
Everolimus, Everolimus placebo, Best Supportive Care (BSC)
Keywords
Gastric cancer,, advanced gastric cancer,, stomach neoplasm,, stomach disease,, adenocarcinoma of stomach,, GI neoplasm
Medical subject headings
Stomach Neoplasms, Stomach Diseases, Digestive System Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called RAD001

    Everolimus was formulated as tablets of 5 mg strength. In both treatment arms, the study drug was given by continuous oral daily dosing of 10 mg (2 tablets x 5 mg) each morning.

  • Everolimus placeboDrug

    Placebo was formulated to be indistinguishable from the everolimus tablets, also formulated as tablets of 5 mg strength. In both treatment arms, the study drug was given by continuous oral daily dosing of 10 mg (2 tablets x 5 mg) each morning.

  • Best Supportive Care (BSC)Drug

    Best supportive care is defined as care in accordance with the local practice of an individual institution or center, specifically excluding anti-cancer treatments.

Study groups in NCT00879333
Study groupRoleWhat they receive
Everolimus + BSCExperimentalAll patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
Receives: Drug: Everolimus; Drug: Best Supportive Care (BSC)
Placebo + BSCPlacebo comparatorAll patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
Receives: Drug: Everolimus placebo; Drug: Best Supportive Care (BSC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS)

    The primary objective of this study was to compare OS between everolimus + best supportive care (BSC) and placebo + BSC. OS, was defined as the time from date of randomization to the date of death due to any cause. If at the analysis cut-off date a patient was not known to have died, survival was censored at the date of the last contact. OS was analyzed using the Kaplan Meier estimates method.

    Measured: 2.5 years

Secondary outcomes (6)
  1. Progression Free Survival (PFS)

    Progression free survival was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, where progression was based on Investigator assessment of baseline and post-baseline scans according to RECIST. Progression free survival was censored if no PFS event was observed before the first to occur out of (i) the cut-off date, or (ii) the date when a further anticancer therapy was started. The censoring date was the date of the last adequate tumor assessment before either of these two events occurred. If a PFS event was observed after two or more missing or non-evaluable tumor assessments, then the date of progression was censored at the date of the last adequate tumor assessment; for a PFS event observed after a single missing or non-evaluable tumor assessment, the actual date of disease progression was used. Anslsis was done using Kaplan-Meier estimates method.

    Measured: 2.5 years

  2. Patient Reported Outcome (PRO): Time to Definitive Deterioration of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Scores

    The EORTC QLQ-C30 global health status/quality of life sub-scale (QL) was pre-specified as the primary domain of interest, followed by physical functioning (PF), social functioning (SF) and emotional functioning (EF).The EORTC QLQ-C30 questionnaire, along with a module specific for gastric cancer patients (EORTC QLQ-STO22), was used to evaluate PRO. The QLQ-C30 has five function scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and a global health status/quality of life scale. In addition, there are questions that assess specific symptoms. The QLQ-STO22 consists of 22 questions that make up five multi-item scales (dysphagia, pain, reflux, eating and anxiety) and four single-item scales (dry mouth, tasting, body image and hair loss).

    Measured: 2.5 years

  3. Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score

    The ECOG PS scale was used to classify patients according to their functional impairment, with scores ranging from 0 (fully active) to 5 (dead). An analysis of the time to definitive deterioration of the ECOG PS by one category of the score from baseline was performed. Definitive deterioration was defined as a definitive increase by one category from baseline in ECOG PS, with no later improvements observed during the course of the study. A single measure reporting an increase in ECOG PS is sufficient to consider it as a definitive worsening only if it was the last one available for the patient. Kaplan-Meier method was used to estimate the distribution function of time to definitive worsening.

    Measured: 2.5 years

  4. Overall Response Rate (ORR)

    ORR was defined as the proportion of patients with measurable disease in whom best overall response (OR) was either complete response (CR) or partial response (PR) according to RECIST criteria.

    Measured: 2.5 years

  5. Everolimus Steady State Concentraions at Predose (Cmin) and Cmax at Week 5

    Cmin is the minimum (trough) steady-state drug concentration in the blood during multiple dosing and Cmax is the maximum (peak) blood drug concentration after dose administration. Cmax is estimated as the maximum of C1h and C2H. C1h is 1 hour post-dose blood concentration and C2h is 2 hour post-dose blood concentration. Only valid pre-dose (Cmin), C1h, and C2h everolimus samples were included in the analysis. Valid pre-dose samples were confirmed blood samples collected at steady-state, collected immediately prior to dosing on the same study day, and collected at approximately 24 ± 4 hours after the previous dose and with no vomiting within the first 4 hours following the last dose. Valid C1h and C2h samples were confirmed blood samples collected at steady-state and within ± 1 hour window and with no vomiting within the first 4 hours following the current and previous dose.

    Measured: Week 5

  6. Everolimus Steady State Concentraions at Predose (Cmin) and Cmax by Region Asia vs. Rest of the World (ROW) at Week 5

    Cmin is the minimum (trough) steady-state drug concentration in the blood during multiple dosing and Cmax is the maximum (peak) blood drug concentration after dose administration. Cmax is estimated as the maximum of C1h and C2H. C1h is 1 hour post-dose blood concentration and C2h is 2 hour post-dose blood concentration. Only valid pre-dose (Cmin), C1h, and C2h everolimus samples were included in the analysis. Valid pre-dose samples were confirmed blood samples collected at steady-state, collected immediately prior to dosing on the same study day, and collected at approximately 24 ± 4 hours after the previous dose and with no vomiting within the first 4 hours following the last dose. Valid C1h and C2h samples were confirmed blood samples collected at steady-state and within ± 1 hour window and with no vomiting within the first 4 hours following the current and previous dose.

    Measured: Week 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Apr 2009 (estimated)
  2. Study startJul 2009
  3. Primary completionJan 2014
  4. Study completionJan 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
656 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00879333
Sponsor's protocol ID
CRAD001R2301
Other IDs
2008-006544-20, 2008
Acronym
GRANITE-1
Status last verified
Oct 2015
First submitted
8 Apr 2009
Last updated
3 Nov 2015
Data monitoring committee
Yes

Publications

  • Ohtsu A, Ajani JA, Bai YX, Bang YJ, Chung HC, Pan HM, Sahmoud T, Shen L, Yeh KH, Chin K, Muro K, Kim YH, Ferry D, Tebbutt NC, Al-Batran SE, Smith H, Costantini C, Rizvi S, Lebwohl D, Van Cutsem E. Everolimus for previously treated advanced gastric cancer: results of the randomized, double-blind, phase III GRANITE-1 study. J Clin Oncol. 2013 Nov 1;31(31):3935-43. doi: 10.1200/JCO.2012.48.3552. Epub 2013 Sep 16.

    PubMed 24043745

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Everolimus in people with Advanced Gastric Cancer, run by Novartis Pharmaceuticals at 122 sites in 22 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 122 sites in France, China, Japan, Australia, United States and 17 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: 2.5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00879333, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2015.

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