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Colorectal NeoplasmsPhase 3COASTNCT01939223

Colorectal Cancer Treated With Adjuvant Regorafenib Versus Placebo After Curative Treatment of Liver Metastases in a Randomized, Double-blind, Placebo-Controlled Phase-III STudy

A Phase 3 study testing Regorafenib (Stivarga, BAY73-4506) in people with Colorectal Neoplasms, run by Bayer at 121 sites in 14 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Neoplasms
What is being tested?
Regorafenib (Stivarga, BAY73-4506)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
25 participants
Where
121 sitesin 14 countries
Study dates
2 Dec 2013to 29 Aug 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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 locations and contacts

121 sites in 14 countries.

121 sites in 14 countries

United States23 sites

  • Study site

    Baltimore, Maryland, 21201-1595

  • Study site

    Buffalo, New York, 14263-0001

  • Study site

    Chattanooga, Tennessee, 37421

  • Study site

    Dallas, Texas, 75390

  • Study site

    Detroit, Michigan, 48202

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Study site

    Germantown, Tennessee, 38138

  • Study site

    Kirkland, Washington, 98034

  • Study site

    Laguna Hills, California, 92653

  • Study site

    Los Angeles, California, 90033

  • Study site

    Los Angeles, California, 90089

  • Study site

    Los Angeles, California, 90095

  • Study site

    New Brunswick, New Jersey, 08903-2681

  • Study site

    New Haven, Connecticut, 06520-8064

  • Study site

    New Orleans, Louisiana, 70121

  • Study site

    New York, New York, 10021

  • Study site

    Omaha, Nebraska, 68106

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    Richmond, Virginia, 23298-0037

  • Study site

    Rochester, Minnesota, 55905

  • Study site

    Seattle, Washington, 98101

  • Study site

    Seattle, Washington, 98109

  • Study site

    Syracuse, New York, 13210

Other trials in United States

Japan21 sites

  • Study site

    Akashi, Hyōgo, 673-8558

  • Study site

    Amagasaki, Hyōgo, 660-8511

  • Study site

    Fukuoka, 810-8563

  • Study site

    Fukuoka, 811-1395

  • Study site

    Fukuoka, 812-8582

  • Study site

    Kasama, Ibaraki, 309-1793

  • Study site

    Kashiwa, Chiba, 277-8577

  • Study site

    Kobe, Hyōgo, 650-0047

  • Study site

    Koto-ku, Tokyo, 135-8550

  • Study site

    Minato-ku, Tokyo, 105-8471

  • Study site

    Mitaka, Tokyo, 181-8611

  • Study site

    Sapporo, Hokkaido, 006-8555

  • Study site

    Sapporo, Hokkaido, 060-0004

  • Study site

    Sapporo, Hokkaido, 060-8648

  • Study site

    Shimotsuke, Tochigi, 329-0498

  • Study site

    Shinagawa, Tokyo, 142-8666

  • Study site

    Shinjuku-ku, Tokyo, 160-8582

  • Study site

    Suita, Osaka, 565-0871

  • Study site

    Sunto, Shizuoka, 411-8777

  • Study site

    Takatsuki, Osaka, 569-8686

  • Study site

    Yokohama, Kanagawa, 241-8515

Other trials in Japan

China18 sites

  • Study site

    Beijing, 100021

  • Study site

    Beijing, 100071

  • Study site

    Beijing, 100142

  • Study site

    Beijing, 100730

  • Study site

    Changsha, Hunan, 410008

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian, 350001

  • Study site

    Guangzhou, Guangdong, 510060

  • Study site

    Guangzhou, Guangdong, 510655

  • Study site

    Hangzhou, Zhejiang, 310009

  • Study site

    Hangzhou, Zhejiang, 310016

  • Study site

    Harbin, Heilongjiang

  • Study site

    Kunming, Yunnan, 650118

  • Study site

    Shanghai, 200030

  • Study site

    Shanghai, 200032

  • Study site

    Shanghai, 200127

  • Study site

    Wuhan, Hubei, 430033

  • Study site

    Xi'an, Shaanxi, 710032

  • Study site

    Xi'an, Shaanxi, 710038

Other trials in China

Italy11 sites

  • Study site

    Brescia, Lombardy, 25124

  • Study site

    Florence, Tuscany, 50134

  • Study site

    Foggia, Apulia, 71013

  • Study site

    Milan, Lombardy, 20089

  • Study site

    Milan, Lombardy, 20133

  • Study site

    Milan, Lombardy, 20141

  • Study site

    Naples, Campania, 80131

  • Study site

    Pisa, Tuscany, 56126

  • Study site

    Reggio Emilia, Emilia-Romagna, 42123

  • Study site

    Rome, Lazio, 00189

  • Study site

    Udine, Friuli Venezia Giulia, 33100

Other trials in Italy

France9 sites

  • Study site

    Bordeaux, 33076

  • Study site

    Brest, 29285

  • Study site

    Clermont-Ferrand, 63000

  • Study site

    Lyon, 69373

  • Study site

    Marseille, 13385

  • Study site

    Paris, 75651

  • Study site

    Poitiers, 86021

  • Study site

    Tours, 37044

  • Study site

    Villejuif, 94800

Other trials in France

Spain9 sites

  • Study site

    Alicante, 03010

  • Study site

    Badajoz, 06080

  • Study site

    Barcelona, 08036

  • Study site

    Córdoba, 14004

  • Study site

    Madrid, 28007

  • Study site

    Madrid, 28034

  • Study site

    Madrid, 28040

  • Study site

    Valencia, 46009

  • Study site

    Valencia, 46013

Other trials in Spain

Germany5 sites

  • Study site

    Berlin, 12200

  • Study site

    Frankfurt am Main, Hesse, 60590

  • Study site

    Mainz, Rhineland-Palatinate, 55131

  • Study site

    München, Bavaria, 81377

  • Study site

    Oldenburg, Lower Saxony, 26133

Other trials in Germany

Australia4 sites

  • Study site

    Bentleigh East, 3165

  • Study site

    East Melbourne, Victoria, 3002

  • Study site

    Liverpool, New South Wales, 2170

  • Study site

    Malvern, 3144

Other trials in Australia

Brazil4 sites

  • Study site

    Belo Horizonte, Minas Gerais, 30110-090

  • Study site

    Porto Alegre, Rio Grande do Sul

  • Study site

    São José do Rio Preto, São Paulo

  • Study site

    São Paulo, São Paulo, 01246-000

Other trials in Brazil

Canada4 sites

  • Study site

    Edmonton, Alberta, T6G 1Z2

  • Study site

    Montreal, H2W 1S6

  • Study site

    Sherbrooke, Quebec, J1H 5N4

  • Study site

    Toronto, Ontario, M5G 1X8

Other trials in Canada

United Kingdom4 sites

  • Study site

    Bristol, BS2 8ED

  • Study site

    London, SW3 6JJ

  • Study site

    London, WC1E 6BT

  • Royal Marsden NHS Trust (Surrey)

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Belgium3 sites

  • Study site

    Edegem, 2650

  • Study site

    Leuven, 3000

  • Study site

    Liège, 4000

Other trials in Belgium

Israel3 sites

  • Study site

    Haifa, 3109601

  • Study site

    Ramat Gan, 52482

  • Study site

    Tel Aviv, 64239

Other trials in Israel

Portugal3 sites

  • Study site

    Almada, 2801-951

  • Study site

    Porto, 4200-072

  • Study site

    Santa Maria da Feira, 4520-531

Other trials in Portugal

About this study

Official 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

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.

Being tested
Regorafenib (Stivarga, BAY73-4506), Placebo
Keywords
Stage IV colorectal cancer / Liver Metastasis
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Regorafenib (Stivarga, BAY73-4506)Drug

    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

  • PlaceboDrug

    Four tablets taken in the morning orally daily for 21 days of treatment followed by 7 days without treatment

Study groups in NCT01939223
Study groupRoleWhat they receive
RegorafenibExperimental4 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.
Receives: Drug: Regorafenib (Stivarga, BAY73-4506)
PlaceboPlacebo comparator4 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Free Survival (DFS) as Assessed by the Investigator

    Disease free survival was evaluated by CT / MRI scans as assessed by the investigator, which was defined as the time (in days) 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. For subjects without documented disease recurrence or death at the time of analysis, the DFS time was censored at the date of the last evaluable CT / MRI scan.

    Measured: 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 outcomes (1)

  1. Overall Survival (OS)

    Overall survival (OS) is defined as the time (days) from randomization to death due to any cause. The OS time for subjects alive at the time of analysis was censored at their last date known to be alive.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2013 (estimated)
  2. Study start2 Dec 2013
  3. Primary completion29 Aug 2016
  4. Study completion29 Aug 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01939223
Sponsor's protocol ID
15983
Other IDs
2012-004369-42
Acronym
COAST
Status last verified
Sep 2017
First submitted
6 Sep 2013
Last updated
20 Oct 2017
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Regorafenib (Stivarga, BAY73-4506) in people with Colorectal Neoplasms, run by Bayer at 121 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 121 sites in United States, Japan, China, Italy, France and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival (DFS) as Assessed by the Investigator (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01939223.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2017.

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