Program Status
Active, not recruitingPhase
Phase 3Prior Immunotherapy Allowed
NoCRC-directed Trial
YesDrugs
Lenvatinib, Pembrolizumab, Regorafenib, TAS-102 (trifluridine and tipiracil)Tags
MSS/ MMRpLocation | Location Status |
---|---|
United States | |
Pacific Cancer Care ( Site 0031) Monterey, California 93940 |
Active, not recruiting |
Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0021) Marietta, Georgia 30060 |
Active, not recruiting |
University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P Chicago, Illinois 60637 |
Active, not recruiting |
MFSMC-HJWCI-Oncology Research ( Site 0012) Baltimore, Maryland 21237 |
Active, not recruiting |
MedStar Good Samaritan Hospital-Oncology Research ( Site 0038) Baltimore, Maryland 21239 |
Active, not recruiting |
Henry Ford Hospital ( Site 0024) Detroit, Michigan 48202 |
Active, not recruiting |
St. Vincent Frontier Cancer Center ( Site 0005) Billings, Montana 59102 |
Active, not recruiting |
Providence Portland Medical Center ( Site 0019) Portland, Oregon 97213 |
Active, not recruiting |
Thomas Jefferson University - Clinical Trials Office ( Site 0027) Philadelphia, Pennsylvania 19107 |
Active, not recruiting |
Inova Schar Cancer Institute ( Site 0022) Fairfax, Virginia 22031 |
Active, not recruiting |
Blue Ridge Cancer Care ( Site 0036) Roanoke, Virginia 24014 |
Active, not recruiting |
Northwest Medical Specialties, PLLC ( Site 0033) Tacoma, Washington 98405 |
Active, not recruiting |
Argentina | |
Hospital Británico de Buenos Aires-Oncology ( Site 0308) Ciudad autónoma de Buenos Aires, Buenos Aires C1280AEB |
Active, not recruiting |
Fundación favaloro para la Docencia e Investigación Médica-Oncología ( Site 0301) Buenos Aires, Caba C1096AAS |
Active, not recruiting |
Instituto de Oncología de Rosario ( Site 0305) Rosario, Santa Fe S2000KZE |
Active, not recruiting |
Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Medical Oncology ( Site 0303) Buenos Aires 1431 |
Active, not recruiting |
IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0300) Buenos Aires C1012AAR |
Active, not recruiting |
Australia | |
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si Brisbane, Queensland 4029 |
Active, not recruiting |
Gallipoli Medical Research Foundation-GMRF CTU ( Site 1500) Greenslopes, Queensland 4120 |
Active, not recruiting |
The Queen Elizabeth Hospital-Cancer Clinical Trials ( Site 1503) Woodville, South Australia 5011 |
Active, not recruiting |
Epworth Freemasons ( Site 1506) Melbourne, Victoria 3002 |
Active, not recruiting |
Western Health-Sunshine & Footscray Hospitals ( Site 1501) St Albans, Victoria 3021 |
Active, not recruiting |
Hollywood Private Hospital-Medical Oncology ( Site 1507) Perth, Western Australia 6009 |
Active, not recruiting |
Canada | |
Cross Cancer Institute-Department of Medical Oncology ( Site 0207) Edmonton, Alberta T6G 1Z2 |
Active, not recruiting |
NSHA-QEII Health Sciences Centre-Dickson Bldg-Dept. of Medical Oncology ( Site 0200) Halifax, Nova Scotia B3H 2Y9 |
Active, not recruiting |
Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0205) Hamilton, Ontario L8V 4X2 |
Active, not recruiting |
North York General Hospital ( Site 0206) Toronto, Ontario M2K1E1 |
Active, not recruiting |
CIUSSS de l'Est-de-l'Île-de-Montréal ( Site 0211) Montreal, Quebec H1T 2M4 |
Active, not recruiting |
CHU de Quebec - Université Laval - Hotel Dieu de Quebec-Hemato-Dermato-Gyneco-Oncology ( Site 0203) Québec, Quebec G1R 3S1 |
Active, not recruiting |
China | |
The First People's Hospital of Foshan-Gastrointestinal oncology ( Site 1604) Foshan, Guangdong 528041 |
Active, not recruiting |
SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1600) Guangzhou, Guangdong 510060 |
Active, not recruiting |
Sir Run Run Shaw Hospital-Medical Oncology ( Site 1606) Hangzhou, Zhejiang 310016 |
Active, not recruiting |
Denmark | |
Rigshospitalet ( Site 0702) Copenhagen, Hovedstaden 2100 |
Active, not recruiting |
Herlev and Gentofte Hospital-Department of Oncology ( Site 0704) Copenhagen, Hovedstaden 2730 |
Active, not recruiting |
Odense Universitetshospital ( Site 0700) Odense, Syddanmark 5000 |
Active, not recruiting |
Vejle Sygehus-Department of Oncology ( Site 0701) Vejle, Syddanmark DK-7100 |
Active, not recruiting |
Germany | |
Klinikum am Steinenberg-Kreiskliniken Reutlingen GmbH ( Site 0908) Reutlingen, Baden-Wurttemberg 72764 |
Active, not recruiting |
klinikum rechts der isar der technischen universität münchen-Klinik und Poliklinik für Innere Mediz Munich, Bayern 81675 |
Active, not recruiting |
Onkodok GmbH ( Site 0907) Gütersloh, Nordrhein-Westfalen 33332 |
Active, not recruiting |
Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0901) Berlin 10117 |
Active, not recruiting |
Asklepios Altona-Oncology ( Site 0903) Hamburg 22763 |
Active, not recruiting |
Israel | |
Rambam Health Care Campus-Oncology ( Site 0800) Haifa 3109601 |
Active, not recruiting |
Shaare Zedek Medical Center-Oncology ( Site 0804) Jerusalem 9013102 |
Active, not recruiting |
Hadassah Medical Center-Oncology ( Site 0802) Jerusalem 9112001 |
Active, not recruiting |
Sheba Medical Center ( Site 0803) Ramat Gan 5262100 |
Active, not recruiting |
Sourasky Medical Center-Oncology ( Site 0801) Tel Aviv 6423906 |
Active, not recruiting |
Japan | |
Aichi Cancer Center Hospital ( Site 1701) Nagoya, Aichi 4648681 |
Active, not recruiting |
National Cancer Center Hospital East ( Site 1700) Kashiwa, Chiba 277-8577 |
Active, not recruiting |
Kobe City Medical Center General Hospital ( Site 1707) Kobe, Hyogo 650-0047 |
Active, not recruiting |
Kagawa University Hospital ( Site 1708) Kita, Kagawa 761-0701 |
Active, not recruiting |
Kanagawa cancer center ( Site 1705) Yokohama, Kanagawa 2418515 |
Active, not recruiting |
Kindai University Hospital- Osakasayama Campus-Medical Oncology ( Site 1704) Osakasayama, Osaka 589-8511 |
Active, not recruiting |
Saitama Prefectural Cancer Center ( Site 1703) Ina-machi, Saitama 362-0806 |
Active, not recruiting |
Shizuoka Cancer Center ( Site 1706) Nagaizumi, Shizuoka 411-8777 |
Active, not recruiting |
National Hospital Organization Kyushu Cancer Center ( Site 1709) Fukuoka 811-1395 |
Active, not recruiting |
National Cancer Center Hospital ( Site 1702) Tokyo 104-0045 |
Active, not recruiting |
Japanese Foundation for Cancer Research-GI Oncology ( Site 1710) Tokyo 135-8550 |
Active, not recruiting |
Korea, Republic of | |
Korea University Anam Hospital ( Site 1806) Seoul 02841 |
Active, not recruiting |
Seoul National University Hospital-Internal Medicine ( Site 1800) Seoul 03080 |
Active, not recruiting |
Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1801) Seoul 03722 |
Active, not recruiting |
Asan Medical Center ( Site 1803) Seoul 05505 |
Active, not recruiting |
Samsung Medical Center-Division of Hematology/Oncology ( Site 1804) Seoul 06351 |
Active, not recruiting |
The Catholic Univ. of Korea Seoul St. Mary's Hospital ( Site 1802) Seoul 06591 |
Active, not recruiting |
Russian Federation | |
GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 1109) Ufa, Baskortostan, Respublika 450054 |
Active, not recruiting |
Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1100) Saint Petersburg, Leningradskaya Oblast 198255 |
Active, not recruiting |
The National Medico-Surgical Center N.I. Pirogov ( Site 1102) Moscow, Moskva 105203 |
Active, not recruiting |
Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 1107) Moscow, Moskva 115478 |
Active, not recruiting |
First Moscow State Medical University I.M. Sechenov-Interhospital Institution ""Health Management ( Moscow, Moskva 119991 |
Active, not recruiting |
SVERDLOVSK REGIONAL ONCOLOGY DISPENSARY ( Site 1108) Ekaterinburg, Sverdlovskaya Oblast 620905 |
Active, not recruiting |
SHBI Leningrad Regional Clinical Oncology Dispensary-Clinical Trials Department ( Site 1111) Sankt-Peterburg 188663 |
Active, not recruiting |
Spain | |
Hospital Universitario Central de Asturias-Digestive ( Site 1200) Oviedo, Asturias 33011 |
Active, not recruiting |
Hospital Universitario Marqués de Valdecilla ( Site 1201) Santander, Cantabria 39008 |
Active, not recruiting |
Hospital Universitari Vall d'Hebron-Oncology ( Site 1204) Barcelona 08035 |
Active, not recruiting |
HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1205) Madrid 28007 |
Active, not recruiting |
Hospital Universitario Virgen de Valme-Departamento de Oncologia ( Site 1207) Sevilla 41014 |
Active, not recruiting |
Taiwan | |
China Medical University Hospital-Surgical Department ( Site 1903) Taichung 40447 |
Active, not recruiting |
NATIONAL CHENG-KUNG UNI. HOSP. ( Site 1904) Tainan 704 |
Active, not recruiting |
National Taiwan University Hospital ( Site 1900) Taipei 10002 |
Active, not recruiting |
Taipei Veterans General Hospital-Oncology ( Site 1901) Taipei 11217 |
Active, not recruiting |
Chang Gung Medical Foundation.Linkou Branch ( Site 1902) Taoyuan 333 |
Active, not recruiting |
Turkey | |
Hacettepe Universitesi-oncology hospital ( Site 1302) Ankara 06230 |
Active, not recruiting |
Memorial Ankara Hastanesi-Medical Oncology ( Site 1304) Ankara 06520 |
Active, not recruiting |
Trakya University-Oncology ( Site 1303) Edirne 22030 |
Active, not recruiting |
Acıbadem Maslak Hastanesi ( Site 1307) İstanbul 34457 |
Active, not recruiting |
Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1300) Istanbul 34668 |
Active, not recruiting |
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1301) Istanbul 34722 |
Active, not recruiting |
Ege University Medicine of Faculty-Medical Oncology ( Site 1305) Izmir 35100 |
Active, not recruiting |
İnönü Üniversitesi Turgut Özal Tıp Merkezi ( Site 1306) Malatya 44280 |
Active, not recruiting |
United Kingdom | |
Addenbrooke's Hospital ( Site 1407) Cambridge, Cambridgeshire CB2 0QQ |
Active, not recruiting |
UCLH-Cancer Clinical Trials Unit ( Site 1400) London, Essex NW1 2PG |
Active, not recruiting |
Guy's & St Thomas' NHS Foundation Trust ( Site 1404) London, London, City Of SE1 9RT |
Active, not recruiting |
ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1403) London, London, City Of SW3 6JJ |
Active, not recruiting |
Western General Hospital ( Site 1401) Edinburgh, Midlothian EH4 2XU |
Active, not recruiting |
Royal Marsden Hospital (Sutton) ( Site 1409) London, Surrey SM3 5PT |
Active, not recruiting |
The Christie-Medical Oncology ( Site 1411) Manchester M20 4BX |
Active, not recruiting |
Inclusion Criteria
Inclusion Criteria:
* Has histologically or cytologically confirmed diagnosis of unresectable and metastatic colorectal adenocarcinoma (Stage IV A, B and C as defined by American Joint Committee on Cancer [AJCC] 8th edition). Note: Tumor must be determined to be NOT microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) by local testing
* Has been previously treated for their disease and has shown disease progression as defined by RECIST 1.1 on or after or could not tolerate standard treatment, which must include ALL of the following agents if approved and locally available in the country where the participant is randomized:
1. fluoropyrimidine, irinotecan and oxaliplatin
2. with or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (bevacizumab)
3. with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) for RAS (KRAS/NRAS) wild-type (WT) participants
4. BRAF inhibitor (in combination with cetuximab +/- binimetinib) for BRAF V600E mutated metastatic colon cancer (mCRC)
* Has measurable disease per RECIST 1.1 assessed by the investigator
* Has provided to a designated central laboratory an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion which has not been previously irradiated
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days prior to randomization
* Has a life expectancy of at least 3 months, based on the investigator assessment
* Has the ability to swallow capsules or ingest a suspension orally or by a feeding tube
* Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 millimeter of mercury (mmHg) with no change in antihypertensive medications within 1 week prior to randomization
* Male participants must agree to the following during the treatment period and for at least 90 days after the last dose of regorafenib or TAS-102 and at least 7 days after the last dose of lenvatinib: refrain from donating sperm PLUS either be abstinent from heterosexual intercourse as their preferred and usual lifestyle or use contraception. The male contraception period should continue for at least 7 days after discontinuation of lenvatinib
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is a WOCBP and using a highly-effective contraceptive method during the treatment period and for at least 30 days after the last dose of lenvatinib, 120 days after the last dose of pembrolizumab, and 180 days after the last dose of regorafenib or TAS-102 (whichever is last) AND agrees not to donate eggs (ova, oocytes)
* A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study treatment
Exclusion Criteria
Exclusion Criteria:
* Has a tumor that is microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) per local testing
* Has presence of gastrointestinal condition, eg, malabsorption, that might affect the absorption of study drug.
* Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
* Has radiographic evidence of encasement or invasion of a major blood vessel invasion or of intratumoral cavitation. In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta
* Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
Participants with cardiac failure NYHA Class II, III and IV are not allowed to be assigned to the regorafenib in Arm B
* Has a history of arterial thromboembolism within 12 months of start of study drug
* Has urine protein ≥1 gram/24 hour
* Has prolongation of QT interval corrected with Fridericia's formula (QTcF interval) to >480 milliseconds
* Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with certain exceptions
* Has serious nonhealing wound, ulcer or bone fracture
* Has had major surgery within 3 weeks prior to first dose of study treatment
* Has received biologic response modifiers (eg, granulocyte colony-stimulating factor) within 4 weeks before study entry
* Has preexisting ≥Grade 3 gastrointestinal or nongastrointestinal fistula
* Has received prior treatment with a combination of an anti-PD-1, anti-PD-L1, or anti PD-L2 agent with anti-VEGF monoclonal antibodies or vascular endothelial growth factor receptor (VEGFR) inhibitors
* Has previously received regorafenib or TAS-102
* Has received prior systemic anti-cancer therapy including investigational agents within 28 days prior to randomization
* Has received prior radiotherapy within 2 weeks of start of study treatment
* Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment
* Has known intolerance to lenvatinib, regorafenib, or TAS-102 and/or any of their excipients
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days prior to the first dose of study treatment
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has an active infection requiring systemic therapy
* Has a known history of Human Immunodeficiency Virus (HIV) infection
* Has a known history of Hepatitis B or known active Hepatitis C virus infection
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Has had an allogenic tissue/solid organ transplant