RECRUITING

Newly Diagnosed Stage III/IV Ovarian Cancer, Neoadjuvant Carbo/taxol/pembro, Maintenance Olaparib/pembro

Conditions

Ovarian Cancer newly diagnosed stage III/IV

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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 trial evaluating three chemotherapy agents in patients with newly diagnosed ovarian cancer patients that are Stage III or Stage IV prior to surgery to remove the tumor. After surgery there will be additional chemotherapy given.

Official Title

A Phase II Study in Newly Diagnosed Stage III/IV Epithelial Ovarian Cancer Evaluating Carbo/Taxol/Pembro in Patients Receiving Neoadjuvant Chemotherapy (NACT) Followed by Olaparib/Pembro Maintenance

Quick Facts

Study Start:2025-02-17

Study Completion:2030-12-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05952453

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
* Participants are eligible to be included in the study only if all of the following criteria apply: 1. Participant has histologically confirmed FIGO Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid, carcinosarcoma, mixed Mullerian with high grade serous component, clear cell, or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer. 2. Participant is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the neoadjuvant setting with planned interval debulking surgery. 3. Participant that is a candidate for neoadjuvant chemotherapy has a CA-125 (kilounits/L) : carcinoembryonic antigen (CEA; ng/mL) ratio greater than or equal to 25 \[Vergote, I., et al 2010\]. 5. Participant is female and at least 18 years of age on the day of signing informed consent. 6. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to enrollment. 7. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: 9. Participant has adequate organ function as follows; all screening laboratory tests should be performed within 7 days of enrollment: 1. Absolute neutrophil count (ANC) ≥1500/μL 2. Platelets ≥100 000/μL 3. Hemoglobin ≥8.0 g/dL or ≥5.6 mmol/L 4. Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥51 mL/min for participant with creatinine levels \>1.5 × institutional ULN 5. Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN 6. AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) 7. International normalized ratio (INR) OR prothrombin time (PT); Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants	* Participants are excluded from the study if any of the following criteria apply: 1. Participant has mucinous, germ cell, or borderline tumor of the ovary. 2. Participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis. 3. Participant either has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML. 4. Participant has a known additional malignancy that is progressing or has required active treatment in the last 3 years. 5. Participant has known active central nervous system metastases and/or carcinomatous meningitis. Participants with brain metastases may participate provided they were previously treated (except with chemotherapy) and are radiologically stable, clinically stable, and no steroids were used for the management of symptoms related to brain metastases within 14 days prior to enrollment. Stable brain metastases should be established prior to the first dose of study medication. 6. Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg dailyof prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to enrollment. 7. Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). 8. Participant has a known history of active tuberculosis (TB; Bacillus Tuberculosis). 9. Participant has an active infection requiring systemic therapy. 10. Participant is considered to be of poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. 11. Participant has had surgery to treat borderline tumors, early stage EOC, or fallopian tube cancer \<6 months prior to screening. 12. Participant has a known psychiatric or substance abuse disorder that would interfere with the ability to cooperate with the requirements of the study. 13. Participant has a known history of human immunodeficiency virus (HIV) infection. 14. Participant has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsag\] reactive) or known active hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. 15. Participant has received prior treatment for advanced or metastatic OC, including radiation or systemic anti-cancer therapy (e.g., chemotherapy, hormonal therapy, immunotherapy, investigational therapy). 16. Participant has severe hypersensitivity (≥Grade 3) to pembrolizumab, olaparib, carboplatin, or paclitaxel, and/or any of their excipients. 17. Participant has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation\>500 ms, electrolyte disturbances, etc.), or participant has congenital long QT syndrome. 18. Participant has had an allogenic tissue/solid organ transplant, has received previous allogenic bone-marrow transplant, or has received double umbilical cord transplantation. 19. Participant has received prior therapy with olaparib or with any other PARP inhibitor. 20. Participant has a known hypersensitivity to the components or excipients in olaparib. 21. Participant is currently receiving either strong (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks. 22. Participant is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents. 23. Participant has received a whole blood transfusion in the last 120 days prior to entry to the study. Packed red blood cells and platelet transfusions are acceptable if not performed within 28 days of the first dose of study intervention. Participant received colony-stimulating factors (e.g., granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GM CSF\] or recombinant erythropoietin) within 28 days prior to the first dose of study intervention. 24. Participant is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption). 25. Participant 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 High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent. 26. Participant has uncontrolled hypertension, defined as defined as systolic \>140 mm Hg or diastolic \>90 mm Hg documented by 2 blood pressure readings taken at least 1 hour apart. 27. Use of antihypertensive medications to control blood pressure is allowed. Participant has current, clinically relevant bowel obstruction (including sub-occlusive disease), abdominal fistula or gastrointestinal perforation, related to underlying EOC. 28. Participant has a history of hemorrhage, hemoptysis or active gastrointestinal bleeding within 6 months prior to enrollment Note: This applies only to participants who will receive bevacizumab. 29. Participant is currently participating or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of the first dose of study treatment. 30. Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.

Inclusion Criteria

Exclusion Criteria

* Participants are eligible to be included in the study only if all of the following criteria apply:
1. Participant has histologically confirmed FIGO Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid, carcinosarcoma, mixed Mullerian with high grade serous component, clear cell, or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer.
2. Participant is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the neoadjuvant setting with planned interval debulking surgery.
3. Participant that is a candidate for neoadjuvant chemotherapy has a CA-125 (kilounits/L) : carcinoembryonic antigen (CEA; ng/mL) ratio greater than or equal to 25 \[Vergote, I., et al 2010\].
5. Participant is female and at least 18 years of age on the day of signing informed consent.
6. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to enrollment.
7. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
9. Participant has adequate organ function as follows; all screening laboratory tests should be performed within 7 days of enrollment:
1. Absolute neutrophil count (ANC) ≥1500/μL
2. Platelets ≥100 000/μL
3. Hemoglobin ≥8.0 g/dL or ≥5.6 mmol/L
4. Creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥51 mL/min for participant with creatinine levels \>1.5 × institutional ULN
5. Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN
6. AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
7. International normalized ratio (INR) OR prothrombin time (PT); Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

* Participants are excluded from the study if any of the following criteria apply:
1. Participant has mucinous, germ cell, or borderline tumor of the ovary.
2. Participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis.
3. Participant either has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML.
4. Participant has a known additional malignancy that is progressing or has required active treatment in the last 3 years.
5. Participant has known active central nervous system metastases and/or carcinomatous meningitis. Participants with brain metastases may participate provided they were previously treated (except with chemotherapy) and are radiologically stable, clinically stable, and no steroids were used for the management of symptoms related to brain metastases within 14 days prior to enrollment. Stable brain metastases should be established prior to the first dose of study medication.
6. Participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg dailyof prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to enrollment.
7. Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
8. Participant has a known history of active tuberculosis (TB; Bacillus Tuberculosis).
9. Participant has an active infection requiring systemic therapy.
10. Participant is considered to be of poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
11. Participant has had surgery to treat borderline tumors, early stage EOC, or fallopian tube cancer \<6 months prior to screening.
12. Participant has a known psychiatric or substance abuse disorder that would interfere with the ability to cooperate with the requirements of the study.
13. Participant has a known history of human immunodeficiency virus (HIV) infection.
14. Participant has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsag\] reactive) or known active hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection.
15. Participant has received prior treatment for advanced or metastatic OC, including radiation or systemic anti-cancer therapy (e.g., chemotherapy, hormonal therapy, immunotherapy, investigational therapy).
16. Participant has severe hypersensitivity (≥Grade 3) to pembrolizumab, olaparib, carboplatin, or paclitaxel, and/or any of their excipients.
17. Participant has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation\>500 ms, electrolyte disturbances, etc.), or participant has congenital long QT syndrome.
18. Participant has had an allogenic tissue/solid organ transplant, has received previous allogenic bone-marrow transplant, or has received double umbilical cord transplantation.
19. Participant has received prior therapy with olaparib or with any other PARP inhibitor.
20. Participant has a known hypersensitivity to the components or excipients in olaparib.
21. Participant is currently receiving either strong (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks.
22. Participant is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
23. Participant has received a whole blood transfusion in the last 120 days prior to entry to the study. Packed red blood cells and platelet transfusions are acceptable if not performed within 28 days of the first dose of study intervention. Participant received colony-stimulating factors (e.g., granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GM CSF\] or recombinant erythropoietin) within 28 days prior to the first dose of study intervention.
24. Participant is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
25. Participant 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 High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
26. Participant has uncontrolled hypertension, defined as defined as systolic \>140 mm Hg or diastolic \>90 mm Hg documented by 2 blood pressure readings taken at least 1 hour apart.
27. Use of antihypertensive medications to control blood pressure is allowed. Participant has current, clinically relevant bowel obstruction (including sub-occlusive disease), abdominal fistula or gastrointestinal perforation, related to underlying EOC.
28. Participant has a history of hemorrhage, hemoptysis or active gastrointestinal bleeding within 6 months prior to enrollment Note: This applies only to participants who will receive bevacizumab.
29. Participant is currently participating or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of the first dose of study treatment.
30. Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.

Contacts and Locations

Study Contact

Margaret Thomas, MPH

CONTACT

2058951802

margaretannthomas@uabmc.edu

Principal Investigator

Rebecca Arend, MD

PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Study Locations (Sites)

O'Neal Comprehensive Cancer Center at UAB

Birmingham, Alabama, 35294

United States

Collaborators and Investigators

Sponsor: University of Alabama at Birmingham

Rebecca Arend, MD, PRINCIPAL_INVESTIGATOR, University of Alabama at Birmingham

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 Date2025-02-17

Study Completion Date2030-12-30

Study Record Updates

Study Start Date2025-02-17

Study Completion Date2030-12-30

Terms related to this study

Keywords Provided by Researchers

newly diagnosed
stage III/IV

Additional Relevant MeSH Terms

Ovarian Cancer