Non‐Randomized, Open‐Label, Prospective Phase II Trial to Better Characterize the Status of HRD leading to a Benefit from Olaparib in Combination with Bevacizumab in Patients with Advanced FIGO Stage III‐IV High Grade Serous or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer After Standard First‐Line Treatment. STROBE

Vall D Hebron Institute Of Oncology12 sites in 1 country100 target enrollmentNovember 8, 2024

DrugsAZD2281 BI 695502 BEVACIZUMABUM BP01 BEVACIZUMAB HLX04 RHUMAB-VEGF OLAPARIB BS-503A RHUMAB VEGF AZD-2281 PF-06439535

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Not specified
Sponsor: Vall D Hebron Institute Of Oncology
Enrollment: 100
Locations: 12
Primary Endpoint: Percentage of HR status agreement between VHIO-CARD-300 test and SOPHiA DDM™ Dx HRD Solution. The corresponding 95% confidence intervals (CI) will be reported.
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

To determine the concordance in HRD status identification between VHIO-CARD-300 test and SOPHiA DDM™ Dx HRD Solution.

Detailed Description

This non-randomized, open-label phase II trial seeks to enhance our understanding of HRD status in patients with advanced ovarian, fallopian tube, or peritoneal cancer. Following standard first-line treatment, participants will be assessed for HRD status using the VHIO-CARD-300 test and SOPHiA DDM™ Dx HRD Solution. Those identified as HRD-positive will receive olaparib in combination with bevacizumab, while others will receive bevacizumab alone as per standard care. The study aims to determine the concordance between the two HRD tests, evaluate the efficacy of the olaparib-bevacizumab combination, and assess safety and tolerability. Efficacy outcomes will be evaluated using RECIST criteria, with a minimum follow-up of 30 months post-enrollment. Secondary objectives include examining treatment accuracy, association with efficacy outcomes, and analyzing discrepant cases. Overall, this trial aims to provide valuable insights into personalized treatment approaches for patients with advanced ovarian cancer.

Registry

euclinicaltrials.eu

Start Date

November 8, 2024

End Date

TBD

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Investigators

Sponsor

Vall D Hebron Institute Of Oncology

Responsible Party

Principal Investigator

Head of Gynaecological Cancer Program

Scientific

Vall D Hebron Institute Of Oncology

Eligibility Criteria

Inclusion Criteria

•Females ≥18 years of age (at the time informed consent is obtained).
•Eastern Cooperative Oncology Group (ECOG) performance status 0-1 within 14 days before enrolment (see Appendix B).
•Patients must have a life expectancy ≥ 16 weeks.
•Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients within 72 hours of receiving the first dose of study medication. Postmenopausal is defined as:  Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments  Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50  radiation-induced oophorectomy with last menses >1 year ago  chemotherapy-induced menopause with >1 year interval since last menses  surgical sterilisation (bilateral oophorectomy or hysterectomy)
•Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
•Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
•Patient with newly diagnosed high- grade serous or endometrioid ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer at an advanced stage: FIGO stage III or IV of the 2014 FIGO classification (see Appendix A).
•Patient who has completed prior to enrolment first line platinum-taxane chemotherapy: a. Platinum-taxane based regimen must have consisted of a minimum of 6 treatment cycles and a maximum of
•However, if platinum-based therapy must be discontinued early as a result of non-haematological toxicity specifically related to the platinum regimen, (i.e., neurotoxicity, hypersensitivity etc.), the patient must have received a minimum of 4 cycles of the platinum regimen. b. Patient must have received prior to enrolment a minimum of 3 cycles of Bevacizumab in combination with the 3 last cycles of platinum-based chemotherapy. Only in case of interval debulking surgery, it is allowed to have received only 2 cycles of Bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy. c. Patients must not have received an investigational agent during their first line course of chemotherapy.
•Patient must be prior to enrolment without evidence of disease (NED) or in complete response (CR) or partial response (PR) from the first-line treatment. There should be no clinical evidence of disease progression (physical exam, imagery, CA-125) throughout her first-line treatment and prior to study enrolment. ‘Response’ is used throughout the protocol and refers to patients being, in the opinion of the Investigator, in clinical CR or PR on the post-treatment scan (at the end of platinum-based chemotherapy). Clinical CR is defined as no evidence of RECIST measurable or nonmeasurable disease on the post-treatment scan and a normal CA-

Exclusion Criteria

•Epithelial ovarian cancer with histologies as clear cell, carcinosarcoma or undifferentiated cancer.
•Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to enrolment.
•History or evidence of haemorrhagic disorders within 6 months prior to enrolment.
•History or clinical suspicion of brain metastases or spinal cord compression.
•nt traumatic injury during 4 weeks prior to enrolment.
•Non-healing wound, active ulcer, or bone fracture.
•History of VEGF therapy related abdominal fistula or gastrointestinal perforation or active gastrointestinal bleeding within 6 months prior to the first study treatment.
•Current, clinically relevant bowel obstruction, including sub-occlusive disease, related to underlying disease.
•Patient with evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
•Resting 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 patients with congenital long QT syndrome.

Outcomes

Primary Outcomes

Percentage of HR status agreement between VHIO-CARD-300 test and SOPHiA DDM™ Dx HRD Solution. The corresponding 95% confidence intervals (CI) will be reported.

Secondary Outcomes

Sensitivity, specificity, predictive positive and negative value of the VHIO-CARD-300 test, using SOPHiA DDM™ Dx HRD Solution as a reference test.
Progression free survival (PFS) and overall survival (OS) will be analysed in HRD and HRP groups, as determined by the VHIOCARD- 300 test. PFS: time from the date of enrolment to the date of first documentation of disease progression or death due to any cause, whichever occurs first. OS: time from the date of enrolment to the date of death due to any cause. The progression of disease will be assessed by the Investigator according to the modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) will be used.
PFS and OS will be analysed in discrepant cases (i.e., HRD positive by VHIO-CARD- 300 test but HRD negative by SOPHiA DDM™ Dx HRD Solution and HRD negative by VHIO-CARD-300 test but HRD positive by SOPHiA DDM™ Dx HRD Solution).
Percentage of inconclusive results will be estimated for each test
Assessment of adverse events (AEs) graded by the National Cancer Institute (NCI) CTCAE v5.0, serious adverse events (SAEs), abnormal vital signs, abnormal ECG results, and evaluation of laboratory parameters.