RECRUITING

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

Conditions

Ovarian Cancer BRCAwt homologous recombination deficiency (HRD)PARP inhibitors homologous recombination repair (HR)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Non-randomized Prospective Phase II Study of Upfront Maintenance Olaparib in Advanced Ovarian Cancer BRCAwt Patients With Known Homologous Recombination Deficiency

Quick Facts

Study Start:2024-01-17

Study Completion:2029-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06120972

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.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	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 \<II 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).

Inclusion Criteria

Exclusion 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.

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 \<II
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).

Contacts and Locations

Study Contact

Kelsey Mitch, RN

CONTACT

412-623-6793

adamkka2@upmc.edu

Joshua Plassmeyer, MS

CONTACT

412-648-6417

plassmeyerjm@upmc.edu

Principal Investigator

Alexander B Olawaiye, MD

PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Study Locations (Sites)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

United States

Collaborators and Investigators

Sponsor: Alexander B Olawaiye, MD

Alexander B Olawaiye, MD, PRINCIPAL_INVESTIGATOR, UPMC Hillman Cancer Center

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 Registration Dates

Study Start Date2024-01-17

Study Completion Date2029-12-31

Study Record Updates

Study Start Date2024-01-17

Study Completion Date2029-12-31

Terms related to this study

Keywords Provided by Researchers

BRCAwt
homologous recombination deficiency (HRD)
PARP inhibitors
homologous recombination repair (HR)

Additional Relevant MeSH Terms

Ovarian Cancer