Efficacy and Safety of Olaparib Olaparib + Bevacizumab Compared to Bevacizumab + 5-Fluorouracil (FU)

  • STATUS
    Recruiting
  • End date
    Jan 22, 2027
  • participants needed
    525
  • sponsor
    Merck Sharp & Dohme Corp.
Updated on 31 July 2021
fluorouracil
oxaliplatin
bevacizumab
folfox regimen
chemotherapy regimen
systemic chemotherapy
adenocarcinoma
solid tumour
colorectal adenocarcinoma

Summary

This is an efficacy and safety study of olaparib alone or in combination with bevacizumab being compared to bevacizumab with Fluorouracil (5-FU) in participants with unresectable or metastatic colorectal cancer (CRC) who have not progressed following first-line induction of FOLFOX with bevacizumab. Hypothesis 1 - Olaparib + Bevacizumab is superior to 5-FU + 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) in the treatment of CRC. Hypothesis 2 - Olaparib is superior to 5-FU + Bevacizumab with respect to PFS using RECIST 1.1 as assessed by BICR) in the treatment of CRC.

Details
Condition Metastatic Colorectal Cancer
Treatment bevacizumab, 5-FU, olaparib
Clinical Study IdentifierNCT04456699
SponsorMerck Sharp & Dohme Corp.
Last Modified on31 July 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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)
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 with bevacizumab as first-line therapy
Participants must not have received an investigational agent during their FOLFOX \+ bevacizumab induction course
Determination of SD/PR/CR will be made by the investigator
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 FOLFOX + bevacizumab induction treatment
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 FOLFOX + bevacizumab (last dose is the day of
the last infusion)
\. Has provided to the imaging contract research organization (iCRO) at least
set of radiographic images taken during the FOLFOX + bevacizumab induction
period and at least 42 days prior to the imaging performed during screening
The iCRO must determine the images are of diagnostic quality prior to
randomization
\. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0
to 1 within 10 days prior to randomization

Exclusion Criteria

Has known hypersensitivity to the components and/or excipients in bevacizumab, 5-FU or olaparib
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
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
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
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 myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or with features suggestive of MDS/AML
Has hemoptysis or hematemesis within 28 days prior to randomization
Has evidence of bleeding diathesis or significant coagulopathy (in the absence of coagulation)
Has clinically significant bleeding within 28 days prior to randomization
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
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
History of nephrotic syndrome or moderate proteinuria
History of gastrointestinal perforation
History of non-gastrointestinal fistula formation
History of possible reversible encephalopathy syndrome (RPLS)
Has received prior systemic anticancer therapy (other than 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 may be eligible
Has received prior therapy with olaparib or with any other polyadenosine 5'-diphosphoribose polymerase (PARP) inhibitor
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
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
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
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