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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01939223




Registration number
NCT01939223
Ethics application status
Date submitted
6/09/2013
Date registered
11/09/2013
Date last updated
20/10/2017

Titles & IDs
Public title
Colorectal Cancer Treated With Adjuvant Regorafenib Versus Placebo After Curative Treatment of Liver Metastases in a Randomized, Double-blind, Placebo-Controlled Phase-III STudy
Scientific title
A Randomized, Double-blind, Placebo-controlled Phase-III Study of Adjuvant Regorafenib Versus Placebo for Patients With Stage IV Colorectal Cancer After Curative Treatment of Liver Metastases
Secondary ID [1] 0 0
2012-004369-42
Secondary ID [2] 0 0
15983
Universal Trial Number (UTN)
Trial acronym
COAST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Regorafenib (Stivarga, BAY73-4506)
Treatment: Drugs - Placebo

Experimental: Regorafenib - 4 regorafenib tablets taken orally in the morning daily, followed by a low fat meal for 3 weeks on off treatment followed by 1 week off without treatment,Treatment 21 days.

Placebo comparator: Placebo - 4 placebo tablets taken orally in the morning daily,followed by a low fat meal for 3 weeks on off treatment followed by 1 week off without treatment,Treatment 21 days.


Treatment: Drugs: Regorafenib (Stivarga, BAY73-4506)
Four tablets of 40mg taken orally daily in the morning, dose of 160 mg for 21 days of treatment followed by 7 days without treatment

Treatment: Drugs: Placebo
Four tablets taken in the morning orally daily for 21 days of treatment followed by 7 days without treatment
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease Free Survival (DFS) as Assessed by the Investigator
Timepoint [1] 0 0
From date of randomization to date of first observed radiographic disease recurrence (RECIST 1.1 criteria for measurable and non-measurable disease) or death due to any cause, if death occurred before disease recurrence was documented.
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Subjects who experienced disease recurrence (either during treatment or during Active Follow-up), or otherwise withdrew from the study for any reason other than death, were followed for overall survival unless consent was withdrawn.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/12/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/08/2016
Sample size
Target
Accrual to date
Final
25
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
- Liverpool
Recruitment hospital [2] 0 0
- East Melbourne
Recruitment hospital [3] 0 0
- Bentleigh East
Recruitment hospital [4] 0 0
- Malvern
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
3165 - Bentleigh East
Recruitment postcode(s) [4] 0 0
3144 - Malvern
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
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Nebraska
Country [8] 0 0
United States of America
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New Jersey
Country [9] 0 0
United States of America
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New York
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North Carolina
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Pennsylvania
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Tennessee
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Texas
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United States of America
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Virginia
Country [15] 0 0
United States of America
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Washington
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Belgium
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Edegem
Country [17] 0 0
Belgium
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Leuven
Country [18] 0 0
Belgium
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Liege
Country [19] 0 0
Brazil
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Minas Gerais
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Brazil
State/province [20] 0 0
Rio Grande do Sul
Country [21] 0 0
Brazil
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Sao Paulo
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Canada
State/province [22] 0 0
Alberta
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
Canada
State/province [25] 0 0
Montreal
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China
State/province [26] 0 0
Fujian
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China
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Guangdong
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China
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Heilongjiang
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China
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Hubei
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China
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Hunan
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China
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Shaanxi
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China
State/province [32] 0 0
Yunnan
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China
State/province [33] 0 0
Zhejiang
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China
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Beijing
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China
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Shanghai
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France
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Bordeaux
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France
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Brest
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France
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Clermont-Ferrand
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France
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LYON Cedex 08
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France
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Marseille
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France
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Paris
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France
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Poitiers Cedex
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France
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Tours
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France
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Villejuif
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Niedersachsen
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Germany
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Rheinland-Pfalz
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Germany
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Berlin
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Israel
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Haifa
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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Campania
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Italy
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Emilia-Romagna
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Italy
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Friuli-Venezia Giulia
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Italy
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Lazio
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Italy
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Lombardia
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Italy
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Puglia
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Italy
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Toscana
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Japan
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Chiba
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Japan
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Hokkaido
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Hyogo
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Japan
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Ibaraki
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Japan
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Kanagawa
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Japan
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Osaka
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Japan
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Shizuoka
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Japan
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Tochigi
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Japan
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Tokyo
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Japan
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Fukuoka
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Portugal
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Almada
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Portugal
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Porto
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Portugal
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Santa Maria da Feira
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Spain
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Alicante
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Spain
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Badajoz
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Spain
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Barcelona
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Spain
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Córdoba
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Spain
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Madrid
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Spain
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Valencia
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United Kingdom
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Surrey
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United Kingdom
State/province [80] 0 0
Bristol
Country [81] 0 0
United Kingdom
State/province [81] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01939223
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01939223