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

NCT00879333 | Completed Phase 3 Results DMC

• 2 other identifiers: CRAD001R23012008-006544-20
• Study Type: interventional
• Target: 656
• Locations: 22 countries
• Sites: 122

Brief 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.

Conditions

Advanced Gastric Cancer

Keywords

Gastric cancer,; advanced gastric cancer,; stomach neoplasm,; stomach disease,; adenocarcinoma of stomach,; GI neoplasm

Outcome Measures

Primary Outcomes (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.

  2.5 years

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  2.5 years

• 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

  2.5 years

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

  2.5 years

• Overall Response Rate (ORR)

  2.5 years

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

  Week 5

Study Arms (2)

Everolimus + BSC

EXPERIMENTAL

All 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.

Drug: Everolimus; Drug: Best Supportive Care (BSC)

Placebo + BSC

PLACEBO COMPARATOR

All 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.

Drug: Everolimus placebo; Drug: Best Supportive Care (BSC)

Interventions

Everolimus DRUG

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.

Also known as: RAD001

Everolimus + BSC

Everolimus placebo DRUG

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.

Placebo + BSC

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.

Everolimus + BSC; Placebo + BSC

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (122)

Highlands Oncology Group DeptofHighlandsOncologyGrp(2)

Fayetteville, Arkansas, 72703, United States

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Loma Linda Oncology Medical Group Loma Linda

Redlands, California, 92374, United States

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Henry Ford Hospital Dept. of Henry Ford Hospital

Detroit, Michigan, 48202-2689, United States

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University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

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University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(4)

Dallas, Texas, 75390-8527, United States

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

Fort Worth, Texas, 76104, United States

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

Houston, Texas, 77030-4009, United States

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University of Washington Cancer Care Seattle Cancer Alliance

Seattle, Washington, 98109-1023, United States

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Novartis Investigative Site

Buenos Aires, Buenos Aires, C1264AAA, Argentina

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Córdoba, Córdoba Province, X5000IUG, Argentina

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Rio Negro, Viedma, 8500, Argentina

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Canberra, Australian Capital Territory, 2605, Australia

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Herston, Queensland, 4029, Australia

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Kurralta Park, South Australia, 5037, Australia

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North Adelaide, South Australia, 5006, Australia

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Box Hill, Victoria, 3128, Australia

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Clayton, Victoria, 3168, Australia

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Footscray, Victoria, 3011, Australia

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Heidelberg, Victoria, 3084, Australia

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Prahran, Victoria, 3181, Australia

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Charleroi, 6000, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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North Vancouver, British Columbia, V7L 2L7, Canada

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Vancouver, British Columbia, V5Z 4E6, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5B 1W8, Canada

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Montreal, Quebec, H3G 1A4, Canada

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Sherbrooke, Quebec, J1H 5N4, Canada

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Guangzhou, Guangdong, 510515, China

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Shijiazhuang, Hebei, 050011, China

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Harbin, Heilongjiang, 150081, China

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Nanjing, Jiangsu, 210002, China

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Suzhou, Jiangsu, 215006, China

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Shenyang, Liaoning, China

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Chengdu, Sichuan, 610041, China

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Hangzhou, Zhejiang, 310016, China

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Beijing, 100036, China

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Beijing, 100039, China

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Guangzhou, 510060, China

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Shanghai, 200003, China

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Shanghai, 200025, China

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Shanghai, 200032, China

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Poitiers, France, 86000, France

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Avignon, 84082, France

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Clermont-Ferrand, 63003, France

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Clichy, 92110, France

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Dijon, 21079, France

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Lyon, 69373, France

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Marseille, 13385, France

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Montpellier, 34298, France

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Nice, 06189, France

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Paris, 75015, France

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Pessac, 33604, France

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Reims, 51092, France

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Rennes, 35062, France

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Toulouse, 31054, France

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Villejuif, 94805, France

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Mannheim, Baden-Wurttemberg, 68305, Germany

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Mainz, Germany, 55131, Germany

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Berlin, 13353, Germany

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Bielefeld, 33604, Germany

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Frankfurt, 60488, Germany

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München, 81675, Germany

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Offenburg, 77652, Germany

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Trier, 54290, Germany

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Hong Kong SAR, Hong Kong

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Jerusalem, 9112001, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 5266202, Israel

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Rehovot, 76100, Israel

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Florence, FI, 50134, Italy

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Rozzano, MI, 20089, Italy

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Modena, MO, 41100, Italy

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Aviano, PN, 33081, Italy

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Frattamaggiore, 80020, Italy

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Nagoya, Aichi-ken, 464-8681, Japan

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Kashiwa, Chiba, 277-8577, 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, 060-8648, Japan

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Sagamihara, Kanagawa, 252-0380, Japan

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Sendai, Miyagi, 980-8574, Japan

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Sayama, Osaka, 589-8511, Japan

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Takatsuki, Osaka, 569-8686, Japan

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Kitaadachi-gun, Saitama, 362-0806, Japan

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Utsunomiya, Tochigi, 320-0834, Japan

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Chuo-ku, Tokyo, 104-0045, Japan

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Koto, Tokyo, 135-8550, Japan

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Mitaka, Tokyo, 181-8611, Japan

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León, Guanajuato, 37000, Mexico

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Mexico City, Mexico City, 14080, Mexico

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Amsterdam, 1105 AZ, Netherlands

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Auckland, New Zealand

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San Borja, Lima region, 41, Peru

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San Isidro, Lima region, 27, Peru

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Moscow, 115478, Russia

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Saint Petersburg, 197758, Russia

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Jeonju, Jeollabuk-do, 561-712, South Korea

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Seoul, Korea, 03722, South Korea

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Seoul, Korea, 05505, South Korea

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Seoul, Korea, 06351, South Korea

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Seoul, Korea, 110 744, South Korea

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Seoul, 136-705, South Korea

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Taegu, 700 - 721, South Korea

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Barcelona, Catalonia, 08035, Spain

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Niaosong Township, Taiwan, 83301, Taiwan

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Taipei, Taiwan, 10048, Taiwan

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Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, 33305, Taiwan

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Liouying Township, Taiwan

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Taipei, Taiwan

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Songkhla, 90110, Thailand

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Northwood, Middlesex, HA6 2RN, United Kingdom

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Sutton, Surrey, SM2 5PT, United Kingdom

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East Yorkshire, HU16 5JQ, United Kingdom

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London, SW3 6JJ, United Kingdom

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London, WC1E 6HX, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Wolverhampton, WV10 0QP, United Kingdom

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Related Publications (1)

• 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.

  PMID: 24043745 DERIVED

Related Links

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

MeSH Terms

Conditions

Stomach Neoplasms; Stomach Diseases; Digestive System Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

4 randomized patients, 2 patients each from the everolimus and placebo arms were excluded from the safety analyses as they did not receive any dose of study treatment.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

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: April 8, 2009
• First Posted: April 10, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: November 3, 2015
• Results First Posted: April 6, 2015

Record last verified: 2015-10

Locations

NL (1); TW (5); BE (4); US (8); DE (8); CN (14); IT (5); AR (3); KR (7); ES (1); AU (9); IL (4); HK (1); CA (6); ME (2); RU (2); TH (3); JP (14); NZ (1); PE (2); GB (7); FR (15)