Ovarian Cancer
Conditions
Keywords
Ovarian cancer, Normothermic Intraperitoneal Chemotherapy, NIPEC, Elderly and frail patients, Intraperitoneal tissue pharmacokinetics, Intraperitoneal tissue responses
Brief summary
The purpose of this feasibility study is to investigate whether NIPEC with carboplatin after surgery is safe for the elderly and frail women with advanced ovarian cancer. To achieve this, women with advanced ovarian cancer who receive surgery followed by NIPEC will be closely monitored in the period after treatment. We will assess complications, side effects, recovery after surgery and NIPEC, and whether standard chemotherapy can be started on time and completed as planned. In addition, participants will be followed for six months using questionnaires and interviews to evaluate patient-reported outcomes, including quality of life. In the more technical assessment of NIPEC, carboplatin tissue pharmacokinetics and inflammatory responses during and after NIPEC will be analysed using microdialysis and histology.
Interventions
DRUGNormethermic Intraperitoneal Chemotherapy with carboplatin
Normothermic Intraperitoneal Chemotherapy is being performed intraoperatively with carboplatin 800mg/m\^2 for 90 min intraperitoneal circulation at normal body temperature 36.5-37.5℃.
Sponsors
Odense University Hospital
University of Aarhus
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent. * Patient capability of giving informed consent. * Age ≥ 70 years. * Women diagnosed with epithelial ovarian cancer, fallopian tube cancer, peritoneal cancer FIGO stage III-IV with planned interval cytoreductive surgery. Stage IV patients will only be included if they have resectable metastases within the abdominal cavity and/or abdominal wall or if they have complete remission of extra-abdominal metastases after three series of neoadjuvant chemotherapy. * Performance status 1-3. * American Society of Anaesthesiologists (ASA) scores I-III. * Normal preoperative kidney, liver and bone marrow function (according to the CTCAE v.5.0): Normal kidney function definition: eGFR or GFR ≥ 60 ml/min. Normal liver function: ALAT and/OR ASAT ≤ 2.5 × ULN; Total bilirubin ≤ 1.5 ×ULN. Normal bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count ≥ 75 × 10⁹/L; Haemoglobin level ≥ 6 mmol/L; * Completeness of cytoreduction to less than 2.5 mm. * Demographically belonging to Region of Southern Denmark.
Exclusion criteria
* Progression of disease during NACT. * Intrabdominal metastases not resectable upon NACT. * Former history of breast cancer or other malignancies within 5 years before inclusion, except from non-melanomatous skin cancer. * Contradictions to receive carboplatin according to the SmPC (the medical oncologist makes the decision): Drug allergy (active drug or components); Severe myelosuppression; Severe kidney deficiency (creatinin clearance ≤ 30 ml/min); Bleeding tumours; Concurrent usage of vaccination against yellow fever; Severe allergic reaction to other platinum compounds in the medical history.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants with Treatment-Related Adverse Events and Adverse Reactions | The day that adjuvant chemotherapy starts (up to 4-6 weeks). | The proportions of participants experiencing perioperative and postoperative complications of adverse events (AEs) of grade 3 to 5 according to the Common Terminology for Adverse Events (CTCAE) version 5.0 and Clavien-Dindo classification (surgical AEs) together with adverse drug reactions (ADRs) related to carboplatin until the day of adjuvant chemotherapy start. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Length of hospital stay | The day of hospital discharge (up to 14 days). | Amount of days that the participant stays at the hospital following cytoreductive surgery and NIPEC. |
| Proportion of reoperations | The day that adjuvant chemotherapy starts (up to 4-6 weeks). | Proportion of patients going through abdominal/gynecological reoperation and cause. |
| Proportion of readmissions. | The day that adjuvant chemotherapy starts (up to 4-6 weeks). | Proportion of patients being readmitted to the hospital and cause. |
| Time from surgery to the first dose of adjuvant systemic chemotherapy. | The day that adjuvant chemotherapy starts (up to 4-6 weeks). | The amount of days from the say of surgery and NIPEC to the first dose of adjuvant systemic chemotherapy. |
| Completion of adjuvant chemotherapy. | At second follow up (3 months). | Proportion of participants completing the adjuvant chemotherapy. |
| Patients' willingness to participate. | At study completion (at 6 months) | Proportion of patients who are asked to participate in the study who provide written informed consent. |
| Patient reported adverse events | At first follow up (up to 6 weeks). | Patient reported outcomes on adverse events assessed by PRO-CTCAE. |
| Change in health-related quality of life using EORCT-questionnaires | Baseline, follow-up 1 (up to 6 weeks), follow-up 2 (3 months) and follow-up 3 (6 months). | Quality of Life (QoL), assessed using the EORTC QLQ-C30 and the disease-specific modules EORTC QLQ-OV28 and EORTC QLQ-CR29, will be measured at baseline and at follow-up 1, 2, and 3. Changes in QoL scores over time will be evaluated by comparing questionnaire scores across the assessment time points. |
| Carboplatin AUC in peritoneum parietale | 30, 60, 90, 120, 150, 180, 210, 240, 300, 360 min. post-dose | Carboplatin Area Under the Plasma Concentration Versus Time Curve in peritoneum parietale measured using microdialysis. |
| Carboplatin Cmax in peritoneum parietale | Up to 360 min. post-dose | Carboplatin maximum concentration in peritoneum parietale measured using microdialysis. |
| Carboplatin Tmax in peritoneum parietale | Up to 360 min. post-dose | Time to carboplatin maximum concentration (Tmax) in peritoneum parietale measured using microdialysis. |
| Carboplatin T½ in peritoneum parietale | Up to 360 min. post-dose | Carboplatin half-life (T½) in peritoneum parietale measured using microdialysis. |
| Carboplatin AUC in tumor tissue | 30, 60, 90, 120, 150, 180, 210, 240, 300, 360 min. post-dose | Carboplatin Area Under the Plasma Concentration Versus Time Curve in peritoneal tumor tissue measured using microdialysis. |
| Carboplatin Cmax in tumor tissue | Up to 360 min. post-dose | Time to carboplatin maximum concentration (Cmax) in tumor tissue measured using microdialysis. |
| Carboplatin Tmax in tumor tissue | Up to 360 min. post-dose | Time to carboplatin maximum concentration (Tmax) in tumor tissue measured using microdialysis. |
| Carboplatin T½ in tumor tissue | Up to 360 min. post-dose | Carboplatin half-life (T½) in tumor tissue measured using microdialysis. |
| Change in inflammatory response in parietal peritoneum | Baseline (before NIPEC) and up to 15 min. post-NIPEC | Inflammatory response will be assessed in peritoneal tissue samples using histopathological and/or molecular markers. Changes associated with intraperitoneal chemotherapy will be evaluated. |
| Change in inflammatory response in tumor tissue | Baseline (before NIPEC) and up to 15 min. post-NIPEC | Inflammatory response will be assessed in tumor tissue samples using histopathological and/or molecular markers. Changes associated with intraperitoneal chemotherapy will be evaluated. |
| Inflammatory protein changes in parietal peritoneum | 90 min and 360 min after NIPEC initiation (post-dose). | Changes in inflammatory protein levels in parietal peritoneum during NIPEC and up to 6 hours post-NIPEC will be measured using microdialysis. |
| Ichemic metabolites changes in parietal peritoneum | 30, 60, 90, 120, 150, 180, 210, 240, 300, 360 min. after NIPEC initiation (post-dose). | Changes in ischemic metabolites (lactate, pyruvate, glucose and glycerol) levels in parietal peritoneum during NIPEC and up to 6 hours post-NIPEC will be measured using microdialysis. |
Countries
Denmark
Contacts
CONTACTLone LKP Kjeld Petersen, MD, DMSc
Outcome results
None listed