Overview

Upfront Maintenance Olaparib in Advanced Ovarian Cancer BRCAwt Patients With Known Homologous Recombination Deficiency

Status:
Recruiting
Trial end date:
2029-12-31
Target enrollment:
0
Participant gender:
Female
Summary
This is a prospective non-randomized efficacy trial of olaparib maintenance therapy after frontline treatment with platinum-based therapy in advanced ovarian cancer patients with BRCAwt, homologous recombination deficient (HRD) disease.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Alexander B Olawaiye, MD
Collaborator:
AstraZeneca
Treatments:
Olaparib
Criteria
Inclusion Criteria:

1. ECOG performance score of 0, 1, or 2

2. Life expectancy ≥ 16 months

3. Normal organ and marrow function as defined below: - Absolute neutrophil count (ANC) ≥
1.5 x 109 /L - Platelets ≥ 100 x 109 /L - Hemoglobin (Hgb) ≥ 8 g/dL (blood
transfusions to reach this amount are allowed) Page 15 of 69 - Serum creatinine ≤ 1.5
mg/dL - Total serum bilirubin ≤ 1.5 x ULN -AST and ALT ≤ 2.5 x ULN

4. Histologically confirmed advanced BRCAwt+ ovarian cancer with known recombinant
deficiency

5. Measurable disease per RECIST 1.1

6. At least one lesion, not previously irradiated, that can be accurately measured at
baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short
axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) or
Clinical examination and, which is suitable for accurate repeated measurements. OR At
least one lesion (measurable and/or non-measurable) that can be accurately assessed at
baseline using CT/MRI/plain x-ray and is suitable for repeated assessment.

Exclusion Criteria:

1. Previous enrollment in the present study

2. Participation in another clinical study with an investigational product (IP) in the
last 3 months.

3. BRCA 1 or 2 germline mutation

4. Use of hyperthermic intraperitoneal chemotherapy as part of their upfront adjuvant
therapy

5. Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (ie germ cell
tumors)

6. Ovarian tumors of low malignant potential (eg borderline tumors) or mucinous carcinoma

7. Synchronous primary endometrial cancer unless both of the following criteria are met:

1. Stage
2. Aged <60 years at the time of diagnosis of endometrial cancer with stage IA or IB
grade I or II, or stage IA grade III endometrial carcinoma OR aged ≥60 years at
the time of diagnosis of endometrial cancer with stage IA grade I or II
endometrioid adenocarcinoma. Subjects with serous or clear cell adenocarcinoma or
carcinosarcoma of the endometrium are not eligible

8. Other malignancy within the last 5 years except adequately treated non-melanoma skin
cancer; curatively treated in situ cancer of the cervix; ductal carcinoma in situ.
Subjects with a history of localized malignancy diagnosed over 5 years ago may be
eligible provided they completed adjuvant systemic therapy prior to enrollment and
remain free of recurrent or metastatic disease.

9. Subjects with a history of primary triple-negative breast cancer may be eligible
provided they completed definitive anticancer treatment more than 3 years ago and
remain breast cancer free prior to start of study treatment

10. Subjects with MDS/ AML history

11. Subjects who experienced, for at least one cycle, a delay of >2 weeks because of
prolonged hematologic recovery during first-line chemotherapy

12. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
reasons) within 3 weeks prior to study treatment Major surgery within 4 weeks of
starting study treatment; subjects must have recovered from any effects of any major
surgery

13. Previous allogenic bone marrow transplantation or double umbilical cord blood
transplantation (dUCBT).

14. Any previous treatment with poly(adenosine diphosphate-ribose) polymerase inhibitor,
including olaparib

15. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy
or antineoplastic hormonal therapy, or simultaneous radiotherapy during the trial
treatment period (hormonal replacement therapy is permitted as are steroidal
antiemetics)

16. Current or recent (within 10 days prior to enrollment) chronic use of aspirin >325
mg/day

17. Concomitant use of known strong cytochrome P450 3A4 (CYP3A4) inhibitors (eg.
itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with
ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or
moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole,
verapamil). The required washout period prior to starting olaparib or study treatment
is 2 weeks.

18. *Concomitant use of known strong (eg.e.g. phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or
moderate CYP3A inducers (eg.e.g. bosentan, efavirenz, modafinil). The required washout
period prior to starting olaparib or study treatment is 5 weeks for enzalutamide or
phenobarbital and 3 weeks for other agents.

19. Clinically significant (eg active) cardiovascular disease, including:

1. Myocardial infarction or unstable angina pectoris within ≤6 months of enrollment

2. New York Heart Association grade ≥2 congestive heart failure

3. Poorly controlled cardiac arrhythmia despite medication (subjects with rate
controlled atrial fibrillation are eligible), or any clinically significant
abnormal finding on resting electrocardiogram

4. Peripheral vascular disease grade ≥3 (eg symptomatic and interfering with
activities of daily living requiring repair or revision)

20. Previous cerebrovascular accident, transient ischemic attack or subarachnoid
hemorrhage within 6 months prior to enrollment

21. History or evidence of hemorrhagic disorders within 6 months prior to enrollment

22. Evidence of bleeding diathesis or significant coagulopathy (in the absence of
coagulation)

23. History or clinical suspicion of untreated brain metastases or spinal cord
compression. Computed tomography (CT)/magnetic resonance imaging (MRI) of the brain is
mandatory (within 4 weeks prior to enrollment) in the case of suspected brain
metastases. Spinal MRI is mandatory (within 4 weeks prior to enrollment) in the case
of suspected spinal cord compression

24. History or evidence upon neurological examination of central nervous system disease
(eg uncontrolled seizures), unless adequately treated with standard medical therapy

25. Significant traumatic injury during 4 weeks prior to enrollment

26. Subjects with evidence of abdominal free air not explained by paracentesis or recent
surgical procedure

27. Evidence of any other disease, metabolic dysfunction, physical examination finding or
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or puts the subject at high risk
for treatment related complications

28. Pregnant or lactating women

29. Subjects unable to swallow orally administered medication and subjects with
gastrointestinal disorders likely to interfere with absorption of the study medication

30. Subjects with a known hypersensitivity to olaparib or any of the excipients of the
product

31. Immunocompromised subjects, for example, with known active hepatitis (ie, hepatitis B
or C) or subjects known to be serologically positive for human immunodeficiency virus.

32. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as
judged by the investigator (eg.e.g., unstable ischemia, uncontrolled symptomatic
arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte
disturbances, etc.), or patients with congenital long QT syndrome.

33. Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2)
caused by previous cancer therapy, excluding alopecia.

34. Patients 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 High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder
that prohibits obtaining informed consent.

35. Whole blood transfusions in the last 120 days prior to entry to the study (packed red
blood cells and platelet transfusions are acceptable, for timing refer to inclusion
criteria no.7).