Pressurized IntraPeritoneal Aerosol Chemotherapy vs. intravenous chemotherapy for unresectable peritoneal metastases secondary to platinum resistant ovarian cancer – study protocol for a randomized control trial

BackgroundDespite optimal surgery and appropriate first-line chemotherapy, ∼70–80 % of patients with epithelial ovarian cancer will develop disease relapse. The prognosis is poor especially for women with Platinum resistant ovarian cancer. The standard treatment for these groups of patients is non-platinum-containing chemotherapy like taxanes, anthracyclines, gemcitabine, topotecan, and trabectedin. These drugs in various combinations and sequences provide modest survival or symptomatic benefit but with significant side effects. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a minimally-invasive drug-delivery technique specifically addressing limited tissue penetration and poor drug distribution with promising results. PIPAC is a novel method of delivering normothermic chemotherapy into the abdominal cavity as an aerosol under pressure. This concept seems to enhance the effectiveness of intra peritoneal chemotherapy by taking advantage of the physical properties of gas and pressure by generating an artificial pressure gradient and enhancing tissue uptake and distributing drugs homogeneously within the closed and expanded peritoneal cavity. Thus, due to the high local bioavailability during PIPAC, the chemotherapy dosage can be reduced which in turn largely prevents systemic side effects and organ toxicity.MethodsThe study aims to investigate the therapeutic efficacy measured as objective tumour response according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria, of PIPAC in comparison with conventional Intravenous chemotherapy for women with recurrent platinum resistant ovarian cancer with peritoneal metastasis (PM). Consecutive patients diagnosed with PM secondary to platinum-resistant ovarian cancer will be randomized to PIPAC group or IV chemotherapy group. The primary objective of this study is to determine the efficacy after three cycles of PIPAC with cisplatin and doxorubicin in comparison with six cycles of systemic chemotherapy. The secondary outcome measures include morbidity and mortality, overall survival and disease specific survival. Analysis is by intention to treat.AimAssess the objective tumour response of PIPAC in comparison with systemic intravenous chemotherapy for women with platinum-resistant ovarian cancer.Study typeProspective randomized control intervention trial.Intervention modelIV Chemotherapy group (Control group) PIPAC group (Experimental group)MaskingOpen label.Primary purposeTreatment.Sample sizeCalculated sample size is 97 and rounded to 100. For each treatment group sample size of 50 will be considered.Primary outcome criteriaObjective tumour response according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1.Secondary outcome criteriaMorbidity;Disease-specific survival (months between inclusion and death due to ovarian cancer);OS (months between inclusion and death due to any cause);CA 125 levels.DiscussionPIPAC in women with platinum resistant ovarian PM has good response owing to superior tissue penetration and better drug distribution. The procedure is safe and well tolerated owing it to its minimal invasiveness. Typical side-effects of systemic chemotherapy, such as alopecia, peripheral neurotoxicity, nausea and myelosuppression are absent. We expect reduction of ascites with symptomatic relief and CA 125 levels. PIPAC is a novel technique for selected patients with platinum resistant ovarian PM and further investigation in comparative clinical trials with conventional chemotherapy will establish its role as a good palliative treatment option.Ethics committee approvalObtained.StatusRecruiting.Trial registration numberREF/2018/08/021223 Registered on Clinical Trials Registry – India (CTRI); www.ctri.nic.in

A phase II trial of durvalumab (Medi 4736) in advanced endometrial cancer: PHAEDRA.

TPS5614 Background: Advanced endometrial cancer (EC) progressing after 1 or more lines of chemotherapy is an area of unmet need with objective tumour response rates to subsequent lines of chemotherapy of ≤20%. DNA mismatch repair (MMR) deficiency, seen in approximately 15% of EC, is associated with a high mutational load and in addition, up to 90% of ECs are reported to have PDL1/ PD1 expressions. These factors make immune check point inhibition an ideal target for treatment. Methods: DESIGN: Multicentre phase 2 trial in two cohorts. ELIGIBILITY: Advanced, unresectable endometrial cancer that is either MMR-proficient and progressing after 1-3 lines of chemotherapy, or MMR-deficient and progressing after 0-3 lines of chemotherapy. ENDPOINTS: Objective tumour response rate (OTRR) according to iRECIST (primary) and RECIST 1.1, disease control rates at 16 and 24 weeks, progression free survival, overall survival, duration of OTR and DC, adverse events, health related quality of life. Tertiary correlative objectives: Associations between immunologic (including PD-L1), DNA mismatch repair (MMR) and other genetic characteristics with clinical outcomes; and family history of cancer and referral to familial cancer services. INTERVENTION: Durvalumab 1500 mg intravenously every 28 days until disease progression or prohibitive toxicity. STATISTICS: Total of 70 participants in two cohorts (35 each) will have 90% power to distinguish a difference in observed OTRR of ≥20% versus ≤5% (uninteresting rate) using Simon’s 2-stage minimax design with 10% type 1 error rate and allowing 10% ineligibility and missing data. Durvalumab will be considered worthy of pursuit if 4 or more OTR are observed in the first 32 participants in each cohort (OTRR ≥12.5%). BIOSPECIMENS: Tumour tissue and serial bloods (5 time points) will be collected for translational research. PHAEDRA is an investigator-initiated, cooperative-group trial led by ANZGOG, in collaboration with NHMRC Clinical Trials Centre, University of Sydney. Australian New Zealand Clinical Trials Registry: Clinical trial information: ACTRN12617000106336.

Immunoregulation of Shenqi Fuzheng Injection Combined with Chemotherapy in Cancer Patients: A Systematic Review and Meta-Analysis

Background. Immunosuppression is a well-recognised complication of chemotherapy in cancer patients. We assemble the clinical evidence that SQI, an adjuvant drug for lung cancer and gastric cancer which was widely prescribed in China, interventions could increase objective tumour response and regulate immunity in cancer patients undergoing chemotherapy. Methods. We undertook a systemic review of the clinical data from randomised controlled trials up to September 2015 in which a SQI intervention was compared with a control arm in patients undergoing conventional chemotherapy. Revman 5.0 Software was used for the data analysis. Results. 49 randomised controlled trials were included in the systematic review. The meta-analysis results demonstrated that the SQI intervention with conventional chemotherapy exhibited better therapeutic efficacy than the conventional chemotherapy group with a statistically significant higher objective tumour response. Cotreatment with SQI could enhance NK, CD3+, CD4+ level, and CD4+/CD8+ ratio comparing with the conventional chemotherapy group. Conclusions. The conclusions of this review might suggest a high risk of bias due to the low quality and the limitation of cancer types in the included trials. A more reliable conclusion regarding the immunoregulation of SQI could be reached based on more trials of higher quality.