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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
Terminated
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
Country [10] 0 0
United States of America
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North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
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United States of America
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Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Belgium
State/province [16] 0 0
Edegem
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Belgium
State/province [18] 0 0
Liege
Country [19] 0 0
Brazil
State/province [19] 0 0
Minas Gerais
Country [20] 0 0
Brazil
State/province [20] 0 0
Rio Grande do Sul
Country [21] 0 0
Brazil
State/province [21] 0 0
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
State/province [28] 0 0
Heilongjiang
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China
State/province [29] 0 0
Hubei
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China
State/province [30] 0 0
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
Country [34] 0 0
China
State/province [34] 0 0
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
State/province [45] 0 0
Bayern
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Germany
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Hessen
Country [47] 0 0
Germany
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Niedersachsen
Country [48] 0 0
Germany
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Rheinland-Pfalz
Country [49] 0 0
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
Country [56] 0 0
Italy
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Lazio
Country [57] 0 0
Italy
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Lombardia
Country [58] 0 0
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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Japan
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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
State/province [65] 0 0
Osaka
Country [66] 0 0
Japan
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Shizuoka
Country [67] 0 0
Japan
State/province [67] 0 0
Tochigi
Country [68] 0 0
Japan
State/province [68] 0 0
Tokyo
Country [69] 0 0
Japan
State/province [69] 0 0
Fukuoka
Country [70] 0 0
Portugal
State/province [70] 0 0
Almada
Country [71] 0 0
Portugal
State/province [71] 0 0
Porto
Country [72] 0 0
Portugal
State/province [72] 0 0
Santa Maria da Feira
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Spain
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Alicante
Country [74] 0 0
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
State/province [79] 0 0
Surrey
Country [80] 0 0
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/ct2/show/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/ct2/show/NCT01939223