Patients With Metastatic Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy

NCT01103323 | Completed Phase 3 Results DMC

• 2 other identifiers: 143872009-012787-14
• Study Type: interventional
• Target: 760
• Locations: 19 countries
• Sites: 171

Brief Summary

This is a randomized, double-blind, placebo-controlled multi-center phase III study to evaluate efficacy and safety of regorafenib in patients with metastatic colorectal cancer (CRC) who have progressed on/after all approved drugs for CRC

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival (OS) was defined as the time (days) from randomization to death due to any cause. Patients alive at the time of analysis were censored at the last date known to be alive. If a patient was lost to follow-up and there was no contact after randomization, this patient was censored at Day 1.

  From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis (IA).

Secondary Outcomes (4)

• Progression-free Survival (Based on Investigator's Assessment)

  From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.

• Objective Tumor Response

  From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.

• Disease Control

  From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.

• Tumor Response

  From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.

Study Arms (2)

Regorafenib (Stivarga, BAY73-4506)+BSC

EXPERIMENTAL

Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus Best Supportive Care(BSC).

Drug: Regorafenib (Stivarga, BAY73-4506); Other: Best Supportive Care (BSC)

Placebo+BSC

PLACEBO COMPARATOR

Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus Best Supportive Care (BSC).

Drug: Placebo; Other: Best Supportive Care (BSC)

Interventions

Regorafenib (Stivarga, BAY73-4506) DRUG

160 mg per oral once daily for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off)

Regorafenib (Stivarga, BAY73-4506)+BSC

Placebo DRUG

matching placebo tablets for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off)

Placebo+BSC

Best Supportive Care (BSC) OTHER

BSC includes any concomitant medications or treatments: antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any other symptomatic therapy necessary to provide BSC, except other investigational anti-tumor agents or anti-neoplastic chemo/hormonal/immuno-therapy.

Placebo+BSC; Regorafenib (Stivarga, BAY73-4506)+BSC

Eligibility Criteria

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

You may qualify if:

• Histological or cytological documentation of adenocarcinoma of the colon or rectum
• Progression during or within 3 months following the last administration of approved standard therapies. Patients treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy
• Patients with measurable or non measurable disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status of \</= 1
• Life expectancy of at least 3 months
• Adequate bone marrow, liver and renal function

You may not qualify if:

• Unstable/uncontrolled cardiac disease
• History of arterial or venous thrombotic or embolic events
• Symptomatic metastatic brain or meningeal tumors
• Patients with evidence or history of bleeding diathesis
• Interstitial lung disease - Persistent proteinuria \>/= grade 3
• Unresolved toxicity \> grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity \</= Grade 2

Sponsors & Collaborators

• Bayer: lead

Study Sites (171)

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Beverly Hills, California, 90211, United States

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Los Angeles, California, 90033, United States

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Los Angeles, California, 90036, United States

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Mission Hills, California, 91345, United States

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Orange, California, 92868, United States

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Redlands, California, 92374, United States

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Santa Maria, California, 93454, United States

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Aventura, Florida, 33180, United States

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Jacksonville, Florida, 32224, United States

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Peoria, Illinois, 61615-7828, United States

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Cedar Rapids, Iowa, 52403, United States

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New Orleans, Louisiana, 70121, United States

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Ann Arbor, Michigan, 48106, United States

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Rochester, Minnesota, 55905, United States

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Saint Cloud, Minnesota, 56303, United States

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Jefferson City, Missouri, 65109, United States

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Neptune City, New Jersey, 07754, United States

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New York, New York, 10011, United States

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Fargo, North Dakota, 58122, United States

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Toledo, Ohio, 43623, United States

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Scranton, Pennsylvania, 18510, United States

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Charleston, South Carolina, 29414, United States

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Sumter, South Carolina, 29150, United States

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Dallas, Texas, 75390-9110, United States

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Salt Lake City, Utah, 84106, United States

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Green Bay, Wisconsin, 54303, United States

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Buenos Aires, Ciudad Auton. de Buenos Aires, C1122AAL, Argentina

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Buenos Aires, Ciudad Auton. de Buenos Aires, C1264AAA, Argentina

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Rosario, Santa Fe Province, S2000PBJ, Argentina

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San Miguel de Tucumán, Tucumán Province, T4000GTB, Argentina

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Capital Federal-Buenos Aires, C1426ANZ, Argentina

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Concord, New South Wales, 2139, Australia

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St Leonards, New South Wales, 2065, Australia

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Woolloogabba, Queensland, 4102, Australia

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Woodville South, South Australia, 5011, Australia

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Footscray, Victoria, 3011, Australia

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Parkville, Victoria, 3050, Australia

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Bruxelles - Brussel, 1000, Belgium

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Bruxelles - Brussel, 1070, Belgium

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Bruxelles - Brussel, 1200, Belgium

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Edegem, 2650, Belgium

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Leuven, 3000, Belgium

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Roeselare, 8800, Belgium

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Fortaleza, Ceará, 60160-230, Brazil

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Salvador, Estado de Bahia, 41830-492, Brazil

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Belo Horizonte, Minas Gerais, 30110-090, Brazil

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Ijuí, Rio Grande do Sul, 98700-000, Brazil

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Vancouver, British Columbia, V5Z 4E6, Canada

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Winnipeg, Manitoba, R2H 2A6, Canada

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Moncton, New Brunswick, E1C 6Z8, Canada

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London, Ontario, N6A 4L6, Canada

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Mississauga, Ontario, L5M 2N1, Canada

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Oshawa, Ontario, L1G 2B9, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Québec, Quebec, G1R 2J6, Canada

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Guangzhou, Guangdong, 510060, China

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Guangzhou, Guangdong, 510515, China

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Nanjing, Jiangsu, 210003, China

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Nanjing, Jiangsu, 210009, China

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Qingdao, Shandong, 266100, China

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Beijing, 100021, China

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Beijing, 100071, China

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Changchun, 130021, China

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Chongqing, 400038, China

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Chongqing, 400042, China

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Fuzhou, 350014, China

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Fuzhou, 350025, China

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Hanghzou, 310009, China

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Ha’erbin, 150040, China

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Shanghai, 200001, China

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Shanghai, 200030, China

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Tianjin, 300060, China

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Brno, 65 653, Czechia

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Hradec Králové, 500 05, Czechia

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Olomouc, 775 20, Czechia

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Prague, 18081, Czechia

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Lille, Lille Cedex, 59020, France

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Avignon, 84000, France

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Le Mans, 72015, France

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Lille, 59037, France

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Marseille, 13005, France

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Montpellier, 34298, France

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Paris, 75651, France

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Reims, 51092, France

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Rennes, 35042, France

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Strasbourg, 67085, France

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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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Karlsruhe, Baden-Wurttemberg, 76137, Germany

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Mannheim, Baden-Wurttemberg, 68167, Germany

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Stuttgart, Baden-Wurttemberg, 70199, Germany

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München, Bavaria, 81377, Germany

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München, Bavaria, 81737, Germany

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München, Bavaria, 81925, Germany

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Hanover, Lower Saxony, 30625, Germany

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Oldenburg, Lower Saxony, 26133, Germany

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Cologne, North Rhine-Westphalia, 50924, Germany

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Essen, North Rhine-Westphalia, 45122, Germany

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Leverkusen, North Rhine-Westphalia, 51375, Germany

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Porta Westfalica, North Rhine-Westphalia, 32457, Germany

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Trier, Rhineland-Palatinate, 54290, Germany

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Dresden, Saxony, 01307, Germany

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Halle, Saxony-Anhalt, 06120, Germany

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Magdeburg, Saxony-Anhalt, 39104, Germany

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Berlin, State of Berlin, 13125, Germany

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Budapest, 1082, Hungary

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Debrecen, 4032, Hungary

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Nyíregyháza, 4400, Hungary

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Szeged, 6725, Hungary

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Zrifin, Israel, 6093000, Israel

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Ashkelon, 7830604, Israel

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Beersheba, 8410101, Israel

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Haifa, 3109601, Israel

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Holon, Israel

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Jerusalem, 9112001, Israel

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Petah Tikva, 4941492, Israel

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Rehovot, 7610001, Israel

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Tel Aviv, 6423906, Israel

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Tel Litwinsky, 5262000, Israel

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Brescia, 25124, Italy

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Genova, 16132, Italy

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Milan, 20133, Italy

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Milan, 20162, Italy

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Modena, 41124, Italy

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Napoli, 80131, Italy

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Pisa, 56126, Italy

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Reggio Emilia, 42100, Italy

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Roma, 00168, Italy

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Nagoya, Aichi-ken, 464-8681, Japan

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Chiba, Chiba, 260-8717, 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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Kochi, Kochi, 781-8555, Japan

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Kumamoto, Kumamoto, 860-8556, Japan

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Osaka, Osaka, 540-0006, Japan

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Sayama, Osaka, 589-8511, Japan

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Takatsuki, Osaka, 569-8686, Japan

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Hidaka, Saitama, 350-1298, Japan

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Kita-Adachigun, Saitama, 362-0806, Japan

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Sunto, Shizuoka, 411-8777, Japan

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Shimotsuke, Tochigi, 329-0498, Japan

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Utsunomiya, Tochigi, 320-0834, Japan

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Bunkyo-ku, Tokyo, 113-8519, Japan

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Chuo-ku, Tokyo, 104-0045, Japan

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Koto-ku, Tokyo, 135-8550, Japan

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Mitaka, Tokyo, 181-8611, Japan

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Amsterdam, 1081 HV, Netherlands

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Hoofddorp, 2134 TM, Netherlands

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Leeuwarden, 8901 BR, Netherlands

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Leiden, 2333 ZA, Netherlands

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Aveiro, Aveiro District, 3810-096, Portugal

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Porto, Porto District, 4099-001, Portugal

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Porto, Porto District, 4200-072, Portugal

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Coimbra, 3030-075, Portugal

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Lisbon, 1649-035, Portugal

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Barcelona, Barcelona, 08035, Spain

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L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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Sabadell, Barcelona, 08208, Spain

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Madrid, Madrid, 28040, Spain

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Madrid, Madrid, 28041, Spain

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Madrid, Madrid, 28046, Spain

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Málaga, Málaga, 29010, Spain

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Seville, Sevilla, 41013, Spain

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Geneva, Canton of Geneva, 1211, Switzerland

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Chur, Kanton Graubünden, 7000, Switzerland

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Ankara, 06500, Turkey (Türkiye)

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Instanbul, 34662, Turkey (Türkiye)

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Istanbul, 34390, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Related Publications (4)

• Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12. doi: 10.1016/S0140-6736(12)61900-X. Epub 2012 Nov 22.

  PMID: 23177514 RESULT

• Mross K, Frost A, Steinbild S, Hedbom S, Buchert M, Fasol U, Unger C, Kratzschmar J, Heinig R, Boix O, Christensen O. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors. Clin Cancer Res. 2012 May 1;18(9):2658-67. doi: 10.1158/1078-0432.CCR-11-1900. Epub 2012 Mar 15.

  PMID: 22421192 RESULT

• Cervantes A, Tabernero J, Garcia-Carbonero R, Sastre J, Feliu J, Carmen Guillen-Ponce, Paredes BG, Carral A, Munoz J. Regorafenib in patients with metastatic colorectal cancer in Spain: from clinical trials to real-world evidence. Future Oncol. 2024;20(20):1401-1413. doi: 10.1080/14796694.2024.2340422. Epub 2024 Jun 11.

  PMID: 38861286 DERIVED

• Tabernero J, Lenz HJ, Siena S, Sobrero A, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Yoshino T, Goldberg RM, Sargent DJ, Wagner A, Laurent D, Teufel M, Jeffers M, Grothey A, Van Cutsem E. Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial. Lancet Oncol. 2015 Aug;16(8):937-48. doi: 10.1016/S1470-2045(15)00138-2. Epub 2015 Jul 13.

  PMID: 26184520 DERIVED

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Limitations and Caveats

At 2nd IA, pre-specified O'Brien-Fleming-type efficacy boundary was crossed. DMC concluded OS result positive and after positive risk benefit assessment, recommended unblinding of study. OS from 2nd IA are the final formal and definitive results.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  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, 2010
• First Posted: April 14, 2010
• Study Start: April 1, 2010
• Primary Completion: July 1, 2011
• Study Completion: January 1, 2014
• Last Updated: June 24, 2015
• Results First Posted: November 19, 2012

Record last verified: 2015-05

Locations

CZ (4); FR (10); CN (17); JP (20); IT (9); CA (9); IL (10); PT (5); CH (2); BR (4); NL (4); BE (6); AR (5); AU (6); DE (18); US (26); TU (4); HU (4); ES (8)