Trial Title:
Newly Diagnosed Stage III/IV Ovarian Cancer, Neoadjuvant Carbo/Taxol/Pembro, Maintenance Olaparib/Pembro
NCT ID:
NCT05952453
Condition:
Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Carboplatin
Conditions: Keywords:
newly diagnosed
stage III/IV
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
single- arm phase II trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
neoadjuvant treatment , followed by surgery, then maintenance chemotherapy
Arm group label:
Carbo/taxol/pembro followed by maintenance of olaparib/pembro post-surgery
Other name:
pembrolizimab
Other name:
taxol
Intervention type:
Drug
Intervention name:
olaparibp, embro
Description:
maintenance chemotherapy : olaparib, pembro
Arm group label:
Carbo/taxol/pembro followed by maintenance of olaparib/pembro post-surgery
Summary:
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.
Detailed description:
This is a single-arm, phase II trial for patients with primary Stage III/IV advanced
epithelial ovarian cancer who will receive neoadjuvant chemotherapy. All patients will
receive a one-cycle lead-in of carboplatin (with or without) paclitaxel followed by three
cycles of carboplatin, paclitaxel, and pembrolizumab prior to interval debulking surgery
(IDS), and three cycles after IDS, followed by olaparib and pembrolizumab maintenance.
Patients will receive a pre-treatment biopsy. The study will be done at 1 site and fresh
tissue will be required pre-treatment as well as at the time of IDS. This tissue will be
used for flow cytometry (to determine populations of cells - ie. Tregs, TILs, NK cells,
MDSCs, DCs and other APCs), RNAseq (specifically looking at "hot" and "cold" signatures),
proteomics (PD-L1 status and other protein expression), and immune score staining (based
on the quantification of CD3 and CD8 both at the tumor center and the margins). The
benefit of this study compared to other on-going upfront studies in ovarian cancer is
that all patients will receive PARP inhibitor and pembrolizumab maintenance. Bevacizumab
will be allowed after interval debulking surgery with the last 2 cycles of chemotherapy
and can be continued as maintenance in these patients. Additionally, if a patient does
not have a CR at the conclusion of their chemotherapy, bevacizumab can be added during
the maintenance period.
Criteria for eligibility:
Criteria:
Inclusion 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].
Note: if the serum CA-125/CEA ratio is less than 25, then a workup should be
negative for the presence of a non-ovarian cancer to determine eligibility
(e.g., breast or gastrointestinal cancers [including CRC]).
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:
a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to
follow contraceptive guidance during the Treatment Period and for at least 120 days
following the last dose of pembrolizumab and olaparib and at least 210 days
following the last dose of chemotherapy 8. The participant (or legally acceptable
representative if applicable) provides written informed consent for the study. The
participant may also provide consent for future biomedical research; however, the
participant may participate in the main study without participating in future
biomedical research.
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
Exclusion Criteria:
- 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.
Note: Participants with basal cell carcinoma of the skin, squamous cell
carcinoma of the skin, or carcinoma in situ (e.g., ductal carcinoma in situ,
cervical carcinoma in situ) that has undergone potentially curative therapy are
not excluded. Additionally, participants with synchronous primary endometrial
cancer or a past history of primary endometrial cancer that met the following
conditions are not excluded: Stage not greater than I-A; no more than
superficial myometrial invasion, without vascular or lymphatic invasion; no
poorly differentiated subtypes, including papillary serous, clear cell or other
FIGO Grade 3 lesions.
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.
Note: Participants with known untreated, asymptomatic brain metastases (i.e.,
no neurological symptoms, no requirement for corticosteroids, no or minimal
surrounding edema, and no lesion >1.5 cm) may participate but will require
regular imaging of the brain as a site of disease.
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).
Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency) is
not considered a form of systemic treatment and is allowed.
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.
Note: a current list of strong/moderate inducers of CYP3A4 can be found at the
following website:
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-
interactions-table-substrates-inhibitors-and-inducers
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.
Note: This applies to participants who will receive bevacizumab.
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.
Note: This applies to participants who will receive bevacizumab.
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.
Gender:
Female
Gender based:
Yes
Gender description:
females
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
O'Neal Comprehensive Cancer Center at UAB
Address:
City:
Birmingham
Zip:
35294
Country:
United States
Contact:
Last name:
Pamela Hardwick, RN
Phone:
205-975-5387
Email:
pamdixon@uab.edu
Investigator:
Last name:
Rebecca Arend, MD, MSPH
Email:
Principal Investigator
Start date:
January 1, 2025
Completion date:
November 30, 2025
Lead sponsor:
Agency:
University of Alabama at Birmingham
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
University of Alabama at Birmingham
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05952453
