Olaparib +/- bevacizumab in CRC with SD/PR/CR from FOLFOX with bevacizumab.
- Conditions
- The treatment of participants with unresectable or metastatic CRC that has not progressed following an induction course of FOLFOX + bevacizumabMedDRA version: 21.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000698-22-LV
- Lead Sponsor
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 525
1. Has a histologically-confirmed metastatic or unresectable (Stage IV as defined by AJCC eighth edition) colorectal adenocarcinoma.
2. Has not progressed 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.
3. Has experienced unacceptable toxicity to oxaliplatin that, in the opinion of the treating physician, requires/required the discontinuation of oxaliplatin. 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).
4. Has provided to the iCRO at least 1 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.
5. Has an ECOG performance status of 0 to 1 within 10 days prior to randomization.
6. Has the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption.
7. Has adequate organ function
8. Has provided a tumor tissue sample deemed acceptable by the central lab for biomarker analysis.
If a sample is not available at screening, a new tissue sample is required to be collected during screening.
Demographics
9. Is male or female, at least 18 years of age, at the time of signing the informed consent.
Male Participants
Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
10. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days (if on Arm 2) or 180 days (if on Arm 1 or Arm 3) after the last dose of study intervention:
• Refrain from donating sperm
PLUS either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
OR
• Must agree to use contraception unless confirmed to be azoospermic vasectomized or secondary to medical cause as detailed below:
Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant.
• Male participants must also agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex.
Female Participants
11. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
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 WOCBP
OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), as described in the protocol during the intervention period and for at least 30 days (if on Arm 2) or 180 days (if on Arm 1 or Arm 3) after the last dose of study intervention and agrees not to do
1. Has known hypersensitivity to the components and/or excipients in bevacizumab, 5-FU, or olaparib
2. Has known active 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 HIV infection
5. Has a known history of or is positive for hepatitis B or hepatitis C
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 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 coagulation)
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, non-malignant 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 HRCT scan or any psychiatric disorder that prohibits obtaining informed consent.
12. Has 1 or more conditions that, in the opinion of the physician, make the participant ineligible for treatment with bevacizumab. These conditions may include:
•Uncontrolled hypertension (SBP >150 mm Hg or DBP >100 mm Hg) or a history of hypertensive crisis or hypertensive encephalopathy
•History of:
-nephrotic syndrome or moderate proteinuria
-gastrointestinal perforation
-non-gastrointestinal fistula formation
-RPLS
13. Has received prior systemic anticancer therapy (other than FOLFOX + bevacizumab induction) including investigational agents within 28 days prior to randomization
14. Has received prior therapy with olaparib or with any other PARP inhibitor
15. Is currently receiving either strong or moderate inhibitors of 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 or moderate 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.
18. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.
Prior/Concurrent Clinical Study Experience
19. 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method