| Eligibility |
Inclusion Criteria:
1. Participants undergoing resection for a suspected newly diagnosed glioblastoma who are
also planned to follow the standard regimen or;
2. Participants who have had a prior resection of histologically diagnosed glioblastoma
(WHO grade IV), defined as participants who have progressed on or following standard
therapy, which includes maximal surgical resection, temozolomide, and fractionated
radiotherapy. Participants will also need to have radiation planned as part of the
post-surgical treatment plan.
3. Participants must have measurable disease preoperatively, defined as at least 1
contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm.
4. Ability to understand and the willingness to sign a written informed consent document
(personally or by the legally authorized representative, if applicable).
5. Participant has voluntarily agreed to participate by giving written informed consent
(personally or via legally authorized representative(s), and assent if applicable).
Written informed consent for the protocol must be obtained prior to any screening
procedures. If consent cannot be expressed in writing, it must be formally documented
and witnessed, ideally via an independent trusted witness.
6. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other procedures.
7. Age =18 at time of consent
8. Have a performance status (PS) of =2 on the Eastern Cooperative Oncology (Group (ECOG)
scale (Oken et al. 1982)
9. Ability to swallow oral medications.
10. Participant has adequate bone marrow and organ function
11. Confirmed negative serum pregnancy test (ß-hCG) before starting study treatment or
participant who is no longer of childbearing potential due to surgical, chemical, or
natural menopause.
12. For females of reproductive potential: use of highly effective contraception for at
least 1 month prior to treatment and agreement to use such a method during study
participation and for an additional 6 months after the end of treatment
administration.
13. For males of reproductive potential: use of condoms or other methods to ensure
effective contraception with partner and for an additional 6 months after the end of
treatment administration. Avoid sperm donation for duration of the study and for an
additional 6 months after the end of treatment administration.
14. Agreement to adhere to Lifestyle Considerations throughout study duration.
15. Participants who received chemotherapy must have recovered (Common Terminology
Criteria for Adverse Events [CTCAE] Grade =1) from the acute effects of chemotherapy
except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A
washout period of at least 21 days is required between last chemotherapy dose and Day
1 (provided the participant did not receive radiotherapy).
16. Females of child-bearing potential must agree not to breastfeed starting at screening,
throughout the study period and for 6 months after final study drug administration
Exclusion Criteria:
1. Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise,
that cannot be discontinued prior to surgery. Therapy with heparin, low molecular
weight heparin (LMWH) or fondaparinux is allowed.
2. Pregnancy or lactation.
3. Known allergic reactions to components of the pamiparib capsule/olaparib.
4. Active infection or fever >38.5°C requiring systemic antibiotic, antifungal or
antiviral therapy within 4 weeks of Day 1.
5. Known to have active (acute or chronic) or uncontrolled severe infection, liver
disease such as cirrhosis, decompensated liver disease, and active and chronic
hepatitis.
6. Known active systemic bacterial infection (requiring intravenous [IV] antibiotics at
time of initiating study treatment), fungal infection, or detectable viral infection
(such as known human immunodeficiency virus positivity or with known active hepatitis
B or C [for example, hepatitis B surface antigen positive]. Screening is not required
for enrollment.
7. Any of the following cardiovascular criteria:
- Current evidence of cardiac ischemia
- Current symptomatic pulmonary embolism
- Acute myocardial infarction = 6 months prior to Day 1
- Heart failure of New York Heart Association Classification III or IV (see Section
13.2) = 6 months prior to Day 1
- Grade = 2 ventricular arrhythmia = 6 months prior to Day 1
- Cerebral vascular accident (CVA) or transient ischemic attack (TIA) = 6 months
prior to Day 1
8. Participant has myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of MDS/AML
9. Participant has serious and/or uncontrolled preexisting medical condition(s) that, in
the judgment of the investigator, would preclude participation in this study (for
example, interstitial lung disease, severe dyspnea at rest or requiring oxygen
therapy, severe renal impairment], history of major surgical resection involving the
stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a
preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
10. Prior therapy with PARP inhibitors.
11. Treatment with another investigational drug or other intervention within 30 days prior
to enrollment or within 5 half-lives of the investigational product, whichever is
longer.
12. For Olaparib participants: Use or anticipated need for food and drugs known to be
strong or moderate CYP3A inducers or inhibitors =10 days (or =5 half-lives, whichever
is the shorter) prior to day 1.
|
