Efficacy and Safety of Olaparib (MK-7339) With or Without Bevacizumab Compared to Bevacizumab With a Fluoropyrimidine in Unresectable or Metastatic Colorectal Cancer (CRC) (MK-7339-003/LYNK-003)

March 1, 2024 updated by: Merck Sharp & Dohme LLC

A Phase 3 Randomized, Open-label Study to Evaluate the Efficacy and Safety of Olaparib Alone or in Combination With Bevacizumab Compared to Bevacizumab With a Fluoropyrimidine in Participants With Unresectable or Metastatic Colorectal Cancer Who Have Not Progressed Following First-line Induction (LYNK-003)

This is an efficacy and safety study of olaparib alone or in combination with bevacizumab being compared to bevacizumab with a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer who have not progressed following first-line induction. The primary hypotheses are: Olaparib + Bevacizumab is superior to a fluoropyrimidine + Bevacizumab with respect to progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR); Olaparib is superior to a fluoropyrimidine + Bevacizumab with respect to PFS using RECIST 1.1 as assessed by BICR. As of amendment 5 study enrollment is being discontinued and study participants randomized to one of the two experimental arms (olaparib plus bevacizumab or olaparib monotherapy) must discontinue study intervention. Participants who are still on study treatment will no longer have tumor response assessments by BICR.

Study Overview

Study Type

Interventional

Enrollment (Actual)

335

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New South Wales
      • Kogarah, New South Wales, Australia, 2217
        • St George Hospital ( Site 0052)
      • Liverpool, New South Wales, Australia, 2170
        • Liverpool Hospital ( Site 0055)
    • Queensland
      • Herston, Queensland, Australia, 4029
        • Royal Brisbane and Women s Hospital ( Site 0054)
    • South Australia
      • Woodville South, South Australia, Australia, 5011
        • Queen Elizabeth Hospital ( Site 0053)
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Health ( Site 0050)
      • Frankston, Victoria, Australia, 3199
        • Peninsula Health Frankston Hospital ( Site 0056)
    • Antwerpen
      • Bonheiden, Antwerpen, Belgium, 2820
        • Imelda vzw ( Site 0110)
      • Brasschaat, Antwerpen, Belgium, 2930
        • AZ Klina ( Site 0106)
      • Edegem, Antwerpen, Belgium, 2650
        • UZ Antwerpen ( Site 0108)
    • Bruxelles-Capitale, Region De
      • Brussels, Bruxelles-Capitale, Region De, Belgium, 1200
        • UCL Saint Luc ( Site 0100)
    • Oost-Vlaanderen
      • Aalst, Oost-Vlaanderen, Belgium, 9300
        • OLV Ziekenhuis ( Site 0109)
      • Gent, Oost-Vlaanderen, Belgium, 9000
        • UZ Gent ( Site 0101)
    • Vlaams-Brabant
      • Leuven, Vlaams-Brabant, Belgium, 3000
        • UZ Gasthuisberg ( Site 0102)
    • West-Vlaanderen
      • Kortrijk, West-Vlaanderen, Belgium, 8500
        • AZ Groeninge ( Site 0105)
    • New Brunswick
      • Fredericton, New Brunswick, Canada, E3B 5N5
        • Dr. Everett Chalmers Regional Hospital ( Site 0204)
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • Moncton Hospital - Horizon Health Network ( Site 0201)
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X6
        • Princess Margaret Cancer Centre ( Site 0209)
    • Quebec
      • Laval, Quebec, Canada, H7M 3L9
        • Hopital Cite de la Sante de Laval ( Site 0203)
      • Montreal, Quebec, Canada, H4A 3J1
        • McGill University Health Centre ( Site 0207)
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0202)
    • Araucania
      • Temuco, Araucania, Chile, 4780000
        • Centro Investigación del Cáncer James Lind ( Site 0251)
    • Region M. De Santiago
      • Santiago, Region M. De Santiago, Chile, 7510032
        • Sociedad Oncovida S.A. ( Site 0250)
      • Santiago, Region M. De Santiago, Chile, 7620002
        • Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0252)
    • Cesar
      • Valledupar, Cesar, Colombia, 200001
        • Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0353)
    • Cordoba
      • Monteria, Cordoba, Colombia, 230002
        • Oncomedica S.A. ( Site 0352)
    • Distrito Capital De Bogota
      • Bogota, Distrito Capital De Bogota, Colombia, 110221
        • Administradora Country SA - Clinica del Country ( Site 0350)
      • Bogota, Distrito Capital De Bogota, Colombia, 110321
        • Instituto Nacional de Cancerologia E.S.E ( Site 0362)
    • Risaralda
      • Pereira, Risaralda, Colombia, 660001
        • Oncologos del Occidente ( Site 0364)
    • Santander
      • Bucaramanga, Santander, Colombia, 681002
        • Fundacion Cardiovascular de Colombia ( Site 0360)
    • Valle Del Cauca
      • Cali, Valle Del Cauca, Colombia, 760042
        • Hemato Oncologos S.A. ( Site 0355)
      • Paris, France, 75015
        • Hopital Europeen Georges Pompidou ( Site 0452)
    • Bas-Rhin
      • Strasbourg, Bas-Rhin, France, 67098
        • C.H.U. de Strasbourg Hopital de Hautepierre ( Site 0464)
    • Bretagne
      • Saint-Herblain, Bretagne, France, 44805
        • Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0455)
    • Doubs
      • Besancon, Doubs, France, 25000
        • CHU Jean Minjoz ( Site 0450)
    • Gironde
      • Pessac Cedex, Gironde, France, 33604
        • CHU Bordeaux Haut-Leveque ( Site 0457)
    • Herault
      • Montpellier, Herault, France, 34295
        • CHU Saint Eloi ( Site 0467)
    • Rhone-Alpes
      • Lyon, Rhone-Alpes, France, 69008
        • Centre Leon Berard ( Site 0459)
      • Berlin, Germany, 10117
        • Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0504)
      • Hamburg, Germany, 20249
        • Facharztzentrum Eppendorf ( Site 0501)
    • Baden-Wurttemberg
      • Ulm, Baden-Wurttemberg, Germany, 89081
        • Universitaetsklinikum Ulm ( Site 0500)
    • Nordrhein-Westfalen
      • Bochum, Nordrhein-Westfalen, Germany, 44791
        • St. Josef und St. Elisabeth Hospital gGmbH-Hematology, oncology and palliative medicine ( Site 0503)
      • Budapest, Hungary, 1122
        • Orszagos Onkologiai Intezet ( Site 1431)
    • Bekes
      • Gyula, Bekes, Hungary, 5700
        • Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 1432)
    • Borsod-Abauj-Zemplen
      • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3526
        • Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce
    • Hajdu-Bihar
      • Debrecen, Hajdu-Bihar, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont ( Site 1426)
    • Jasz-Nagykun-Szolnok
      • Szolnok, Jasz-Nagykun-Szolnok, Hungary, 5000
        • Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1427)
    • Zala
      • Zalaegerszeg, Zala, Hungary, 8900
        • Zala Megyei Szent Rafael Korhaz ( Site 1429)
      • Chiba, Japan, 260-8717
        • Chiba Cancer Center ( Site 0656)
      • Fukuoka, Japan, 811-1395
        • National Hospital Organization Kyushu Cancer Center ( Site 0654)
      • Tokyo, Japan, 104-0045
        • National Cancer Center Hospital ( Site 0651)
      • Tokyo, Japan, 135-8550
        • The Cancer Institute Hospital of JFCR ( Site 0659)
    • Aichi
      • Nagoya, Aichi, Japan, 464-8681
        • Aichi Cancer Center Hospital ( Site 0658)
    • Chiba
      • Kashiwa, Chiba, Japan, 2778577
        • National Cancer Center Hospital East ( Site 0650)
    • Ehime
      • Matsuyama, Ehime, Japan, 791-0280
        • National Hospital Organization Shikoku Cancer Center ( Site 0652)
    • Kanagawa
      • Kawasaki, Kanagawa, Japan, 216-8511
        • St. Marianna University School of Medicine Hospital ( Site 0657)
    • Saitama
      • Kitaadachi-gun, Saitama, Japan, 362-0806
        • Saitama Cancer Center ( Site 0653)
    • Shizuoka
      • Sunto-gun, Shizuoka, Japan, 411-8777
        • Shizuoka Cancer Center Hospital and Research Institute ( Site 0655)
      • Seoul, Korea, Republic of, 02841
        • Korea University Anam Hospital ( Site 0955)
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital ( Site 0950)
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital Yonsei University Health System ( Site 0951)
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center ( Site 0954)
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea St. Mary s Hospital ( Site 0953)
    • Seoul
      • Songpagu, Seoul, Korea, Republic of, 05505
        • Asan Medical Center ( Site 0952)
    • Taegu-Kwangyokshi
      • Daegu, Taegu-Kwangyokshi, Korea, Republic of, 41404
        • Kyungpook National University Chilgok Hospital ( Site 0956)
      • Daugavpils, Latvia, 5417
        • Daugavpils Regional Hospital ( Site 1502)
      • Riga, Latvia, LV-1002
        • P. Stradina Clinical University Hospital ( Site 1500)
      • Riga, Latvia, LV-1079
        • Riga East Clinical University Hospital ( Site 1501)
      • Kaunas, Lithuania, 50161
        • LSMUL Kauno Klinikos ( Site 1528)
      • Vilnius, Lithuania, 08406
        • Nacionalinis Vezio Institutas ( Site 1527)
      • Vilnius, Lithuania, 08460
        • Vilniaus Universiteto Ligonine Santaros Klinikos ( Site 1526)
    • Arkhangel Skaya Oblast
      • Arkhangelsk, Arkhangel Skaya Oblast, Russian Federation, 163045
        • Arkhangelsk Clinical Oncological Dispensary ( Site 1113)
    • Baskortostan, Respublika
      • Ufa, Baskortostan, Respublika, Russian Federation, 450054
        • GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 1130)
    • Krasnoyarskiy Kray
      • Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation, 660133
        • Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1121)
    • Moskovskaya Oblast
      • Krasnogorsk, Moskovskaya Oblast, Russian Federation, 143442
        • MEDSI Clinical Hospital on Pyatnitsky Highway-Departmentof Antitumor Drug therapy ( Site 1129)
    • Moskva
      • Moscow, Moskva, Russian Federation, 105203
        • National Medical and Surgical Center n.a. N.I.Pirogov ( Site 1126)
      • Moscow, Moskva, Russian Federation, 115478
        • N.N. Blokhin NMRCO ( Site 1106)
      • Moscow, Moskva, Russian Federation, 119991
        • First Moscow State Medical University n.a. I.M.Sechenov ( Site 1127)
      • Moscow, Moskva, Russian Federation, 125284
        • MROI n.a. P.A. Herzen - branch of FSBI NMICR of MoH of Russia ( Site 1128)
    • Sankt-Peterburg
      • Saint Petersburg, Sankt-Peterburg, Russian Federation, 198255
        • City Clinical Oncology Center ( Site 1114)
    • Gauteng
      • Sandton, Gauteng, South Africa, 2196
        • Sandton Oncology Medical Group PTY LTD ( Site 0900)
    • Limpopo
      • Durban, Limpopo, South Africa, 4001
        • The Oncology Centre ( Site 0903)
    • Western Cape
      • Rondebosch, Western Cape, South Africa, 7700
        • Cancercare Rondebosch Oncology ( Site 0904)
      • Barcelona, Spain, 08035
        • Hospital Vall D Hebron ( Site 1151)
      • Madrid, Spain, 28009
        • Hospital Universitario Gregorio Maranon ( Site 1152)
      • Madrid, Spain, 28041
        • Hospital 12 de Octubre de Madrid ( Site 1150)
    • Alicante
      • Elche, Alicante, Spain, 03203
        • Hospital General Universitario de Elche ( Site 1155)
    • Asturias
      • Oviedo, Asturias, Spain, 33011
        • Hospital Universitario Central de Asturias ( Site 1153)
      • Adana, Turkey, 01250
        • Baskent University Adana Training Hospital ( Site 1205)
      • Ankara, Turkey, 06230
        • Hacettepe University Faculty of Medicine ( Site 1200)
      • Ankara, Turkey, 06500
        • Gazi Universitesi Tip Fakultesi ( Site 1215)
      • Edirne, Turkey, 22030
        • Trakya Universitesi Tip Fakultesi ( Site 1210)
      • Istanbul, Turkey, 34098
        • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1202)
      • Istanbul, Turkey, 34384
        • Prof. Dr. Cemil Tascioglu Sehir Hastanesi ( Site 1216)
      • Istanbul, Turkey, 34722
        • Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1214)
      • Istanbul, Turkey, 34890
        • Kartal Dr. Lutfi Kirdar Egitim ve Arast Hast ( Site 1211)
      • Izmir, Turkey, 35040
        • Ege Universitesi Tip Fakultesi Tulay Aktas Onkoloji Hastanesi ( Site 1204)
      • Konya, Turkey, 42080
        • Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 1203)
    • Adana
      • Malatya, Adana, Turkey, 44280
        • Inonu Universitesi Medical Fakultesi ( Site 1207)
      • Kyiv, Ukraine, 03151
        • Dobrobut Medical Center ( Site 1320)
    • Dnipropetrovska Oblast
      • Dnipro, Dnipropetrovska Oblast, Ukraine, 49055
        • Medical center Medikal Plaza of Ecodnipro LLC ( Site 1317)
    • Kharkivska Oblast
      • Kharkiv, Kharkivska Oblast, Ukraine, 61070
        • Communal non profit enterprise Regional Clinical Oncology Center ( Site 1304)
    • Kyivska Oblast
      • Kapitanivka Village, Kyivska Oblast, Ukraine, 08111
        • Medical Center of Yuriy Spizhenko LLC.-Clinical Trial ( Site 1319)
      • Khodosivka, Kyivska Oblast, Ukraine, 08173
        • Medical Center Asklepion LLC ( Site 1309)
      • Kyiv, Kyivska Oblast, Ukraine, 03039
        • Medical Center Verum ( Site 1318)
      • Kyiv, Kyivska Oblast, Ukraine, 03126
        • Shalimov s NI of Surgery and Transplantation ( Site 1321)
    • Zaporizka Oblast
      • Zaporizhzhia, Zaporizka Oblast, Ukraine, 69035
        • Medical center of the Limited Liability Company Yulis ( Site 1314)
    • California
      • Burbank, California, United States, 91505
        • Providence Saint Joseph Medical Center, Disney Family Cancer ( Site 1392)
      • Fullerton, California, United States, 92835
        • St Joseph Heritage Healthcare-Oncology ( Site 1383)
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • UC Health Memorial Hospital ( Site 1401)
      • Fort Collins, Colorado, United States, 80528
        • Poudre Valley Health System ( Site 1402)
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Cancer & Blood Center, LLC ( Site 1381)
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago ( Site 1357)
      • Peoria, Illinois, United States, 61615
        • Illinois Cancer Care, PC ( Site 1352)
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • James Graham Brown Cancer Center ( Site 1393)
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • University Medical Center New Orleans ( Site 1365)
    • Maine
      • Scarborough, Maine, United States, 04074
        • New England Cancer Specialists ( Site 1422)
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Cancer & Hematology Centers of Western Michigan ( Site 1358)
    • Mississippi
      • Hattiesburg, Mississippi, United States, 39401
        • Hattiesburg Clinic Hematology/Oncology ( Site 1418)
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University in St. Louis ( Site 1384)
    • Montana
      • Billings, Montana, United States, 59102
        • St. Vincent Frontier Cancer Center-Research ( Site 1414)
    • Nebraska
      • Grand Island, Nebraska, United States, 68803
        • CHI Health St. Francis ( Site 1406)
      • Lincoln, Nebraska, United States, 68510
        • Cancer Partners of Nebraska ( Site 1353)
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center ( Site 1400)
      • Portland, Oregon, United States, 97232
        • Oregon Health & Science University ( Site 1411)
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny Singer Research Institute ( Site 1364)
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • West Cancer Center - East Campus ( Site 1396)
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center ( Site 1362)
    • Texas
      • Temple, Texas, United States, 76508
        • Baylor Scott & White Medical Center - Temple ( Site 1397)
    • Virginia
      • Roanoke, Virginia, United States, 24014
        • Blue Ridge Cancer Care ( Site 1374)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Has a histologically-confirmed metastatic or unresectable (Stage IV as defined by American Joint Committee on Cancer (AJCC eighth edition) colorectal adenocarcinoma (National Comprehensive Cancer Network [NCCN] 2018).
  2. Has not progressed (ie, achieved a stable disease [SD], partial response [PR], or complete response [CR]) after a first-line induction course of at least 6 cycles of FOLFOX + bevacizumab or 4 cycles of CAPOX + bevacizumab as first-line therapy.

    • Participants must not have received an investigational agent during their induction course.
    • Determination of best overall response (SD/PR/CR) will be made by the investigator.
    • Non-PD will be verified by BICR prior to randomization based on the images submitted to imaging contract research organization (iCRO) as described in inclusion criterion 4.
    • "First-line therapy" is defined as the first systemic chemotherapy regimen given for the diagnosis of unresectable or metastatic CRC. Participants may have received prior adjuvant/neoadjuvant chemotherapy for CRC, as long as it was completed at least 6 months prior to initiation of first-line CAPOX + bevacizumab or FOLFOX + bevacizumab induction treatment.
  3. Has experienced unacceptable toxicity to oxaliplatin that, in the opinion of the treating physician, requires/required the discontinuation of oxaliplatin. Note: As an example, unacceptable toxicity may include (but is not limited to) severe or prolonged neurotoxicity.

    • Participants must be randomized within a minimum of 2 weeks and a maximum of 6 weeks after their last dose of CAPOX + bevacizumab or FOLFOX + bevacizumab (last dose is the day of the last infusion that contained oxaliplatin).

  4. Has provided to the iCRO 1 set of baseline radiographic images taken before or during the CAPOX + bevacizumab or FOLFOX + bevacizumab induction period and at least 42 days prior to the imaging performed during Screening. Tumor imaging at Screening must be performed within 28 days prior to the date of randomization.
  5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days prior to randomization.

Exclusion Criteria:

  1. Has known hypersensitivity to the components and/or excipients in bevacizumab, 5-FU, capecitabine, or olaparib.
  2. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression for at least 28 days by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid intervention for at least 14 days prior to first dose of study intervention.
  3. Has an active infection requiring systemic therapy.
  4. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
  5. Has a known history of or is positive for hepatitis B surface antigen (HBsAg reactive) or hepatitis C ribonucleic acid (HCV RNA [qualitative]) is detected). Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority.
  6. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
  7. Has myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or with features suggestive of MDS/AML.
  8. Has hemoptysis or hematemesis within 28 days prior to randomization.
  9. Has evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation).
  10. Has clinically significant bleeding within 28 days prior to randomization.
  11. Is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high-resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
  12. Has 1 or more conditions that, in the opinion of the treating physician, make the participant ineligible for treatment with bevacizumab. These conditions may include:

    • Uncontrolled hypertension (systolic blood pressure [SBP] >150 mm Hg or diastolic blood pressure [DBP] >100 mm Hg) or a history of hypertensive crisis or hypertensive encephalopathy
    • Arterial thromboembolic events (eg, myocardial infarction, cerebral infarction)
    • History of nephrotic syndrome or moderate proteinuria
    • History of gastrointestinal perforation
    • History of non-gastrointestinal fistula formation
    • History of possible reversible encephalopathy syndrome (RPLS)
  13. Has received prior systemic anticancer therapy (other than CAPOX + bevacizumab or FOLFOX + bevacizumab induction) including investigational agents within 28 days prior to randomization. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with persistent alopecia or Grade ≤3 neuropathy are eligible.
  14. Has received prior therapy with olaparib or with any other polyadenosine 5'-diphosphoribose polymerase (PARP) inhibitor.
  15. Is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 3A4 (CYP3A4) that cannot be discontinued for the duration of the study. The required washout period prior to randomization is 2 weeks.
  16. Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to randomization is 5 weeks for phenobarbital and 3 weeks for other agents.
  17. Has undergone major surgery within 2 weeks of randomization or has not recovered adequately from toxicities and/or complications from any major surgery prior to randomization.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Olaparib + bevacizumab
Participants will receive olaparib (300 mg twice daily [BID] oral) + Bevacizumab (5 mg/kg intravenous [IV] once every 2 weeks [Q2W]) until progressive disease or end of study.
300 mg BID, oral until progressive disease or end of study
Other Names:
  • LYNPARZA^TM
5 mg/kg or 7.5 mg/kg Q2W or Q3W IV infusion until progressive disease or end of study
Other Names:
  • Avastin
  • MVASI^TM
Experimental: Olaparib
Participants will receive olaparib (300 mg BID) oral, until progressive disease or end of study.
300 mg BID, oral until progressive disease or end of study
Other Names:
  • LYNPARZA^TM
Active Comparator: Bevacizumab + chemotherapy
Participants will receive investigator's choice of either bevacizumab (7.5 mg/kg IV once every three weeks (Q3W)) + capecitabine (1000 mg/m^2 BID for 14 days, then 7 days off, Q3W) or bevacizumab (5 mg/kg IV Q2W) + 5-FU (2400 mg/m2 IV over 46 to 48 hours Q2W; bolus 5-FU (400 mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion). Leucovorin or levoleucovorin 400 mg/m^2 (leucovorin) or 200 mg/m^2 (levoleucovorin) Q2W IV infusion may be added per investigator's discretion. Treatment will continue until progressive disease or end of study.
5 mg/kg or 7.5 mg/kg Q2W or Q3W IV infusion until progressive disease or end of study
Other Names:
  • Avastin
  • MVASI^TM
2400 mg/m^2 over 46 to 48 hours Q2W IV infusion until disease progression or end of study; bolus 5-FU (400mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion
Other Names:
  • Adrucil
  • Fluorouracil
  • Efudex
1000 mg/m^2 oral capsule BID for 14 days, then 7 days off, Q3W) until progressive disease or end of study
Other Names:
  • XELODA^®
400 mg/m^2 (leucovorin) or 200 mg/m^2 (levoleucovorin) may be added to Bevacizumab + 5-FU per investigator's discretion Q2W IV infusion until progressive disease or end of study
Other Names:
  • Folinic Acid
  • Fusilev^®
  • Khapzory^TM

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS Using RECIST 1.1 as Assessed by BICR
Time Frame: Up to ~6 years
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered PD.
Up to ~6 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to ~6 years
Overall survival is the time from randomization to death due to any cause.
Up to ~6 years
Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR
Time Frame: Up to ~6 years
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Up to ~6 years
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Time Frame: Up to ~6 years
For participants who demonstrate a confirmed CR or confirmed PR per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death.
Up to ~6 years
Number of Participants with One or More Adverse Events (AE)
Time Frame: Up to ~6 years
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention
Up to ~6 years
Number of Participants Discontinuing Study Intervention Due to an AE
Time Frame: Up to ~6 years
Tolerability is defined by the degree to which overt AEs of a drug can be tolerated by a participant without discontinuing from the study.
Up to ~6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 19, 2020

Primary Completion (Actual)

March 27, 2023

Study Completion (Actual)

November 6, 2023

Study Registration Dates

First Submitted

July 1, 2020

First Submitted That Met QC Criteria

July 1, 2020

First Posted (Actual)

July 2, 2020

Study Record Updates

Last Update Posted (Actual)

March 4, 2024

Last Update Submitted That Met QC Criteria

March 1, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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