Trial Condition(s):

Colorectal Neoplasms

Colorectal Cancer Treated with Adjuvant Regorafenib Versus Placebo After Curative Treatment of Liver Metastases in a Randomized, Double-blind, Placebo‑controlled Phase-III STudy (COAST)

Bayer Identifier:

15983

ClinicalTrials.gov Identifier:

NCT01939223

EudraCT Number:

2012-004369-42

Terminated/Withdrawn

Trial Purpose

To evaluate and compare the efficacy and safety of regorafenib versus placebo in subjects with colorectal cancer (CRC) after curative resection of liver metastasis and completion of all planned chemotherapy.

Inclusion Criteria
-  Have a history of a primary adenocarcinoma of the colon and / or rectum
-  Have a history of Stage IV Colorectal Cancer (CRC) with metastases to the liver only
-  Have received at least 3 months ,of neoadjuvant, adjuvant, or perioperative chemotherapy, including a fluoropyrimidine and either oxaliplatin or irinotecan or both for subjects with initial Stage IV CRC which were treated with surgery with curative intent for both primary and metastatic lesions.  The total chemotherapy administered, including that administered prior to and after liver resection, should not exceed 9 months. OR Have received surgery with curative intent for primary CRC and at least 3 months ,of neoadjuvant, adjuvant, or perioperative chemotherapy for the primary tumor, including a fluoropyrimidine or a fluoropyrimidine and either oxaliplatin or irinotecan or both
 -- For subjects with liver metastases developing > 6 months after completing treatment for primary CRC and having undergone surgery with curative intent for liver metastases, a second course of chemotherapy lasting at least 3 months needs to be administered, including a fluoropyrimidine and either oxaliplatin or irinotecan or both.  The second course of chemotherapy should not exceed 9 months. 
 - For subjects who developed liver metastases >/=6 months after completing treatment for primary CRC and having undergone surgery with curative intent for liver metastases, a second course of chemotherapy is not permitted unless initial adjuvant therapy consisted of fluoropyrimidine monotherapy.  Subjects who received fluoropyrimidine alone must have received a second course of chemotherapy with fluoropyrimidine and either oxaliplatin or irinotecan or both, which should not exceed 9 months.For subjects with initial Stage I or II disease, no chemotherapy is required for a primary CRC lesion treated with surgery with curative intent.  These subjects must receive chemotherapy for the treatment of liver metastases (which were also treated with surgery with curative intent), which must last at least 3 months, including a fluoropyrimidine and either oxaliplatin or irinotecan or both.  The total course of chemotherapy should not exceed 9 months.
 - Prior to randomization, have histological confirmation that CRC lesions were adenocarcinoma (subtypes of adenocarcinoma, e.g. mucinous adenocarcinoma are allowed). Subjects with CRC lesions of other histological types, including mixed type with predominant adenocarcinoma, will not be eligible to be randomized to study treatment.
 -  Have pathology-proven complete removal of all primary and liver metastatic CRC lesions. Subjects with positive margins will not be eligible for the study.
 - Have adequate bone marrow function, liver function, and renal function, as measured by the following laboratory assessments conducted within 7 days prior to the initiation of study treatment:
 -- Total bilirubin </=1.5 times the upper limit of normal (ULN)
 -- Alanine aminotransferase and aspartate aminotransferase </= 3 times the ULN 
 -- Lipase</=1.5 times the ULN
 -- Serum creatinine</=1.5 times the ULN 
 -- Carcinoembryonic antigen (CEA)</=3 times the ULN
 -- Glomerular filtration rate>/=30 mL/min/1.73 m2 according to the Modified Diet in Renal Disease abbreviated formula 
 -- International normalized ratio of prothrombin time and activated partial thromboplastic time </=1.5 times the ULN.  Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no underlying abnormality in coagulation parameters exists per medical history.
 -- Platelet count >/=100,000 /mm3, hemoglobin >/=9 g/dL, absolute neutrophil count >/= 1500/mm3 without transfusions or granulocyte colony stimulating factor and other hematopoietic growth factors 
 -- Alkaline phosphatase ≤ 2.5 times the ULN
 - Have had a CT or MRI scan (chest, abdomen, pelvis and other suspected sites as applicable) to determine eligibility for randomization within 4 weeks prior to randomization (hereafter referred to as the “eligibility scan”)
  - Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days prior to the initiation of study treatment
 - If female and of childbearing potential, or if male, agree to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double barrier method) based on the judgment of the investigator or a designated associate from the date on which the ICF is signed until  8 weeks after the last dose of study drug.
Exclusion Criteria
- Are taking strong cytochrome P (CYP) CYP3A4 inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole) or strong CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John’s Wort).
 - Have used biologic response modifiers, such as granulocyte-colony stimulating factor, within 3 weeks prior to signing the ICF.
 -  Have had prior treatment with regorafenib or any other (vascular endothelial growth factor receptor) VEGFR-targeting kinase inhibitor.
 -  Have had anti-cancer treatment following liver resection that exceeded a duration of 6 months.
 - Have been treated with biologics (eg, antibodies targeting VEGFR or EGFR) after liver resection unless the administration of the biologic started prior to liver resection and continued after liver resection only to complete a pre-specified number of cycles.
 - Completed their last dose of chemotherapy or had their last cancer surgery more than 10 weeks, whichever came later, prior to randomization.
 -  Have extra-hepatic metastatic disease. Suspicious lesions should be rigorously evaluated with other imaging techniques and/or biopsy to exclude extra-hepatic metastatic disease prior to submitting for central radiology review.
 - Have had systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and/or hormonal therapy within 4 weeks prior to initiation of study treatment.
 - Are pregnant and or breast feeding.
 - Have had prior or concurrent cancer distinct in primary site or histology from CRC within 5 years prior to randomization EXCEPT for curatively treated cervical cancer in situ, nonmelanoma skin cancer, Stage 0 intramucosal gastric cancer after endoscopic complete removal,  or superficial bladder tumors classified as noninvasive tumor (Ta), carcinoma in situ (Tis), or tumor invades lamina propria (T1).
 - Have congestive heart failure classified as New York Heart Association Class 2 or higher.Have had unstable angina (angina symptoms at rest) or new-onset angina ≤  3 months prior to screening. Have had a myocardial infarction <   6 months prior to initiation of study treatment.
 - Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin.
 - Have uncontrolled hypertension (systolic blood pressure [SBP] greater than140 mmHg or diastolic blood pressure [DBP] greater than 90 mmHg) despite optimal medical management.
 - Have pheochromocytoma.
 - Have had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months prior to the initiation of study treatment.
 - Have a known history of human immunodeficiency virus infection.
 - Have either active or chronic hepatitis B or C requiring treatment with antiviral therapy.
 - Have a seizure disorder requiring medication.
 - Have evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity.
 - Have had a hemorrhage or a bleeding event >/=Grade 3 (NCI-CTCAE v 4.0) within 4 weeks prior to the initiation of study treatment.
 - Have any other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject’s participation in the study or evaluation of the study results.

Trial Summary

Enrollment Goal
25
Trial Dates
black-arrow
Phase
3
Could I receive a placebo?
Yes
Products
Stivarga (Regorafenib, BAY73-4506)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

Investigative Site

Haifa, Israel, 3109601

Status
Terminated
 
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Investigative Site

Tel Aviv, Israel, 64239

Status
Completed
 
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Investigative Site

Ramat Gan, Israel, 52482

Status
Completed
 
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Investigative Site

Oldenburg, Germany, 26133

Status
Terminated
 
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Investigative Site

München, Germany, 81377

Status
Terminated
 
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Investigative Site

Frankfurt, Germany, 60590

Status
Terminated
 
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Investigative Site

Berlin, Germany, 12200

Status
Terminated
 
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Investigative Site

Pisa, Italy, 56126

Status
Completed
 
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Investigative Site

Milano, Italy, 20089

Status
Terminated
 
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Investigative Site

Roma, Italy, 00189

Status
Terminated
 
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Investigative Site

Foggia, Italy, 71013

Status
Terminated
 
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Investigative Site

Napoli, Italy, 80131

Status
Completed
 
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Milano, Italy, 20133

Status
Completed
 
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Investigative Site

Reggio Emilia, Italy, 42123

Status
Terminated
 
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Investigative Site

Udine, Italy, 33100

Status
Terminated
 
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Investigative Site

Napoli, Italy, 80131

Status
Terminated
 
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Investigative Site

Firenze, Italy, 50134

Status
Terminated
 
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Investigative Site

Bentleigh East, Australia, 3165

Status
Terminated
 
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East Melbourne, Australia, 3002

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Terminated
 
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Liverpool, Australia, 2170

Status
Completed
 
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Malvern, Australia, 3144

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Terminated
 
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Investigative Site

Belo Horizonte, Brazil, 30110-090

Status
Terminated
 
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São José do Rio Preto, Brazil

Status
Terminated
 
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Investigative Site

Porto Alegre, Brazil

Status
Terminated
 
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Royal Marsden NHS Trust (Surrey)

Sutton, United Kingdom, SM2 5PT

Status
Terminated
 
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Investigative Site

London, United Kingdom, WC1E 6BT

Status
Terminated
 
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Investigative Site

Bristol, United Kingdom, BS2 8ED

Status
Completed
 
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Investigative Site

Córdoba, Spain, 14004

Status
Completed
 
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Valencia, Spain, 46009

Status
Completed
 
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Madrid, Spain, 28007

Status
Terminated
 
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Investigative Site

Madrid, Spain, 28034

Status
Completed
 
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Investigative Site

Alicante, Spain, 03010

Status
Completed
 
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Investigative Site

Madrid, Spain, 28040

Status
Terminated
 
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Investigative Site

Laguna Hills, United States, 92653

Status
Terminated
 
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Investigative Site

Seattle, United States, 98101

Status
Terminated
 
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Investigative Site

Buffalo, United States, 14263-0001

Status
Terminated
 
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Investigative Site

Omaha, United States, 68106

Status
Terminated
 
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Investigative Site

Chattanooga, United States, 37421

Status
Completed
 
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Investigative Site

LYON Cedex 08, France, 69373

Status
Completed
 
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Investigative Site

Marseille, France, 13385

Status
Terminated
 
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Investigative Site

POITIERS CEDEX, France, 86021

Status
Terminated
 
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Clermont-Ferrand, France, 63000

Status
Terminated
 
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Investigative Site

PARIS, France, 75651

Status
Terminated
 
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Investigative Site

TOURS, France, 37044

Status
Terminated
 
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Investigative Site

Bordeaux, France, 33076

Status
Terminated
 
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Investigative Site

BREST, France, 29285

Status
Terminated
 
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Investigative Site

LEUVEN, Belgium, 3000

Status
Terminated
 
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Investigative Site

EDEGEM, Belgium, 2650

Status
Terminated
 
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Investigative Site

LIEGE, Belgium, 4000

Status
Terminated
 
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Investigative Site

New Orleans, United States, 70121

Status
Terminated
 
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Investigative Site

Rochester, United States, 55905

Status
Completed
 
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Investigative Site

New Haven, United States, 06520-8064

Status
Completed
 
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Investigative Site

Detroit, United States, 48202

Status
Terminated
 
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Investigative Site

Los Angeles, United States, 90089

Status
Terminated
 
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Investigative Site

Richmond, United States, 23298-0037

Status
Completed
 
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Investigative Site

New York, United States, 10021

Status
Completed
 
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Investigative Site

Philadelphia, United States, 19104

Status
Terminated
 
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Investigative Site

Baltimore, United States, 21201-1595

Status
Terminated
 
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Investigative Site

New Brunswick, United States, 08903-2681

Status
Terminated
 
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Investigative Site

Syracuse, United States, 13210

Status
Terminated
 
Locations

Duke University Medical Center

Durham, United States, 27710

Status
Terminated
 
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Investigative Site

Los Angeles, United States, 90095

Status
Terminated
 
Locations

Investigative Site

Porto, Portugal, 4200-072

Status
Terminated
 
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Investigative Site

Almada, Portugal, 2801-951

Status
Terminated
 
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Investigative Site

Santa Maria da Feira, Portugal, 4520-531

Status
Terminated
 
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Investigative Site

Seattle, United States, 98109

Status
Terminated
 
Locations

Investigative Site

Los Angeles, United States, 90033

Status
Terminated
 
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Investigative Site

Dallas, United States, 75390

Status
Terminated
 
Locations

Investigative Site

Kirkland, United States, 98034

Status
Terminated
 
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Investigative Site

Toronto, Canada, M5G 1X8

Status
Terminated
 
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Investigative Site

Montreal, Canada, H2W 1S6

Status
Terminated
 
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Investigative Site

Edmonton, Canada, T6G 1Z2

Status
Terminated
 
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Investigative Site

London, United Kingdom, SW3 6JJ

Status
Terminated
 
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Investigative Site

Sherbrooke, Canada, J1H 5N4

Status
Terminated
 
Locations

Investigative Site

Kashiwa, Japan, 277-8577

Status
Terminated
 
Locations

Investigative Site

Koto-ku, Japan, 135-8550

Status
Completed
 
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Investigative Site

Mitaka, Japan, 181-8611

Status
Terminated
 
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Investigative Site

Minato-ku, Japan, 105-8471

Status
Terminated
 
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Investigative Site

Shinagawa, Japan, 142-8666

Status
Completed
 
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Investigative Site

Shinjuku-ku, Japan, 160-8582

Status
Terminated
 
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Investigative Site

Yokohama, Japan, 241-8515

Status
Terminated
 
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Investigative Site

Shimotsuke, Japan, 329-0498

Status
Terminated
 
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Investigative Site

Kasama, Japan, 309-1793

Status
Completed
 
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Investigative Site

Sunto, Japan, 411-8777

Status
Completed
 
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Investigative Site

Suita, Japan, 565-0871

Status
Completed
 
Locations

Investigative Site

Takatsuki, Japan, 569-8686

Status
Terminated
 
Locations

Investigative Site

Kobe, Japan, 650-0047

Status
Completed
 
Locations

Investigative Site

Fukuoka, Japan, 812-8582

Status
Terminated
 
Locations

Investigative Site

Fukuoka, Japan, 811-1395

Status
Terminated
 
Locations

Investigative Site

Sapporo, Japan, 060-8648

Status
Terminated
 
Locations

Investigative Site

Sapporo, Japan, 060-0004

Status
Terminated
 
Locations

Investigative Site

Brescia, Italy, 25124

Status
Terminated
 
Locations

Investigative Site

Fukuoka, Japan, 810-8563

Status
Terminated
 
Locations

Investigative Site

Akashi, Japan, 673-8558

Status
Completed
 
Locations

Investigative Site

Sapporo, Japan, 006-8555

Status
Completed
 
Locations

Investigative Site

Amagasaki, Japan, 660-8511

Status
Completed
 
Locations

Investigative Site

Barcelona, Spain, 08036

Status
Completed
 
Locations

Investigative Site

Milano, Italy, 20141

Status
Terminated
 
Locations

Investigative Site

Germantown, United States, 38138

Status
Terminated
 
Locations

Investigative Site

Badajoz, Spain, 06080

Status
Completed
 
Locations

Investigative Site

Valencia, Spain, 46013

Status
Terminated
 
Locations

Investigative Site

São Paulo, Brazil, 01246-000

Status
Terminated
 
Locations

Investigative Site

Guangzhou, China, 510060

Status
Terminated
 
Locations

Investigative Site

Beijing, China, 100071

Status
Terminated
 
Locations

Investigative Site

Xi'an, China, 710032

Status
Terminated
 
Locations

Investigative Site

Beijing, China, 100142

Status
Terminated
 
Locations

Investigative Site

Hangzhou, China, 310016

Status
Terminated
 
Locations

Investigative Site

Hangzhou, China, 310009

Status
Completed
 
Locations

Investigative Site

Harbin, China

Status
Terminated
 
Locations

Investigative Site

Wuhan, China, 430033

Status
Terminated
 
Locations

Investigative Site

Shanghai, China, 200030

Status
Terminated
 
Locations

Investigative Site

VILLEJUIF, France, 94800

Status
Terminated
 
Locations

Investigative Site

Xi'an, China, 710038

Status
Terminated
 
Locations

Investigative Site

Shanghai, China, 200032

Status
Terminated
 
Locations

Investigative Site

Beijing, China, 100730

Status
Terminated
 
Locations

Investigative Site

Changsha, China, 410008

Status
Terminated
 
Locations

Investigative Site

Kunming, China, 650118

Status
Terminated
 
Locations

Investigative Site

Shanghai, China, 200127

Status
Terminated
 
Locations

Investigative Site

Guangzhou, China, 510655

Status
Terminated
 
Locations

Fujian Medical University Union Hospital

Fuzhou, China, 350001

Status
Terminated
 
Locations

Investigative Site

Mainz, Germany, 55131

Status
Terminated
 
Locations

Investigative Site

Beijing, China, 100021

Status
Terminated
 

Trial Design