💬In plain words
What the trial is, and whether it could suit you
The PROOV study is an open-label, monocenter, single-arm, prospective phase I/II trial with a safety lead-in, evaluating the feasibility of combining PARPi with HIPEC in stage III EOC patients. Phase I is a dose-finding phase with a time-to-event Bayesian Optimal Interval (TITE-BOIN) design, in which three doses of olaparib are evaluated to identify the optimal dose for the phase II part and future trials. The recommended phase II dose (RP2D) will be determined based on the experienced DLTs per dose level and the level of intra-tumor and systemic enzymatic PARP inhibition. During Phase II, the safety profile of the RP2D will be assessed in a total cohort of 40 patients. To provide a proof-of-concept, efficacy will be explored in both translational analyses and survival data.
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria:
* In order to be eligible to participate in this study, a subject must meet all of the following criteria:
* Signed and written informed consent
* At least 18 years of age and able to understand patients' information
* FIGO stage III primary high-grade serous ovarian, fallopian tube, or extra-ovarian cancer.
* FIGO stage IV is allowed in the following situations:
* Resectable stage IV desease, such as local bowel involvement, iatrogenic abdominal wall metastases or umbilical lesions
* Stage IV based on cardiophrenic lymph nodes \<1cm
* The diagnosis should be confirmed with either histology or cytology. If the diagnosis of ovarian carcinoma is based on cytology only, immunohistochemistry, including keratin 7, keratin 20, p53, PAX8 should be considered for confirmation of the diagnosis (at the discretion of the pathologist)
* Eligible and planned for interval cytoreductive surgery with HIPEC
* Neo-adjuvant chemotherapy consists of at least 3 courses of carboplatin/paclitaxel
* Patients should have response or stable disease after NACT; no progression should occur
* Operability has been evaluated in a multidisciplinary team (MDT) meeting via CT scan, MRI or diagnostic laparoscopy and an optimal or complete interval CRS is deemed feasible
* Fit for major surgery, WHO performance status 0-2
* Adequate bone marrow function (hemoglobin level \>5.5 mmol/L, leukocytes \>3 x10\^9/L, platelets \> 100 x10\^9/L)
* Adequate hepatic function (ALT, AST, and bilirubin \< 2.5 times the upper limit of normal)
* Adequate renal function (creatinine clearance ≥ 60 ml/min using Cockcroft-Gault formula or 24-hour measurement or ml/min/1,73 m2 using MDRD or CKD-EPI)
Exclusion Criteria:
* A potential subject who meets any of the following criteria will be excluded from participation in this study:
* History of previous malignancy treated with chemotherapy
* Opting for fertility-sparing surgery
* Concurrent use of potent inducers or inhibitors of CYP3A4 as assessed with the KNMP "G-standaard" that cannot be stopped temporarily
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