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

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
S. P. Somashekhar ◽  
K. R. Ashwin ◽  
Amit Rauthan ◽  
Kumar C. Rohit
Keyword(s):  
Ovarian Cancer ◽  
Side Effects ◽  
Sample Size ◽  
Tumour Response ◽  
Drug Distribution ◽  
Ca 125 ◽  
Secondary Outcome ◽  
Intravenous Chemotherapy ◽  
Objective Tumour Response ◽  
Platinum Resistant

AbstractBackgroundDespite 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

Pressurized intra peritoneal aerosol chemotherapy (PIPAC) vs. intravenous chemotherapy to assess quality of life & response rates in unresectable peritoneal metastases secondary to platinum resistant ovarian cancer: A comparative study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18091-e18091
Author(s):  
S.P. Somashekhar ◽  
Rohit Kumar C. ◽  
Ashwin K. Rajgopal ◽  
Amit Rauthan ◽  
Poonam Patil ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Peritoneal Metastasis ◽  
Pegylated Liposomal Doxorubicin ◽  
Response Rates ◽  
Life Assessment ◽  
Ca 125 ◽  
Intravenous Chemotherapy ◽  
Platinum Resistant

e18091 Background: The primary objective of this study is to assess Qol & response rates in platinum resistant ovarian cancer patients with peritoneal metastasis treated with PIPAC procedure in comparison with conventional systemic intravenous chemotherapy. Methods: Between October 2017 and December 2019, 31 PIPAC applications were done in 15 patients with cisplatin 10.5mg/m2 and doxorubicin 2.1mg/m2. During same period 20 patients received systemic chemotherapy with clinician’s choice of drug ((mono-therapy consisting of pegylated liposomal doxorubicin or topotecan or gemcitabine or paclitaxel weekly with or without bevacizumab).The response rate (With MRI & Ca-125) & quality of life assessment (QLQ C-30) of both the group was done periodically and recorded. Results: Overall 35 patients were analysed in this study. The results have been presented in Table. Conclusions: PIPAC in comparison to intravenous chemotherapy for platinum resistant ovarian cancer with peritoneal metastasis showed better response rates (66.6 vs. 22.4%) and improved quality of life score. PIPAC has shown promising results and should be in the arsenal of the clinicians managing patients with platinum resistant ovarian cancer. [Table: see text]

Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5599-TPS5599
Author(s):  
Rebecca Christian Arend ◽  
Bradley J. Monk ◽  
Thomas J. Herzog ◽  
Jonathan A. Ledermann ◽  
Kathleen N. Moore ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Antiangiogenic Therapy ◽  
Objective Response ◽  
Phase Iii ◽  
Weekly Paclitaxel ◽  
Ca 125 ◽  
Recist 1.1 ◽  
Platinum Resistant ◽  
Phase Iii Study

TPS5599 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism of action that includes a broad antiangiogenic effect and induction of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer showed that VB-111 in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58% with a trend for improved survival. The favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent platinum-resistant epithelial ovarian cancer with measurable disease (RECIST 1.1), and may have been previously treated with up to 5 prior lines of therapy. Patient are randomized 1:1 to receive VB-111 (1x1013 VPs) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The efficacy endpoints are OS, PFS and ORR by RECIST 1.1 and by CA-125 (GCIG criteria). A pre-planned interim analysis was performed by the DSMC in the first 60 patients evaluable for CA-125 response. The analysis met the pre-defined criteria of a CA-125 ORR (GCIG) in the treatment arm at least 10% higher than in the control arm. Study enrolment is ongoing and over 220 patients were enrolled in the US, EU, and Israel. Enrolment of the full sample size of 400 patients is expected to complete by the end of 2021. Clinical trial information: NCT03398655.

Phase II study of vinorelbine in patients with pretreated advanced ovarian cancer: activity in platinum-resistant disease.

1996 ◽  
Vol 14 (9) ◽  
pp. 2546-2551 ◽  
Author(s):  
E Bajetta ◽  
A Di Leo ◽  
L Biganzoli ◽  
L Mariani ◽  
F Cappuzzo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Cancer Patients ◽  
Response Rate ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Ca 125 ◽  
Resistant Disease ◽  
Platinum Resistant ◽  
Exact Confidence Interval

PURPOSE The aim of the study was to evaluate the activity of vinorelbine (VNLB) in a population of advanced ovarian cancer patients, with particular attention to defining its role in platinum-resistant disease. PATIENTS AND METHODS Thirty-three patients were recruited and treated with VNLB 25 mg/m2 intravenously (IV) weekly. the median age was 53 years, performance status 0 to 2, and number of previous chemotherapy regimens two (range, one to five). Twenty-four patients were platinum-resistant; the remaining nine either were platinum-sensitive (four cases) or had undetermined sensitivity (five cases). RESULTS The mean delivered dose-intensity of VNLB was 67% of the planned level, because 60% of the cycles were delayed due to neutropenia or anemia. Four partial responses (PRs) and one complete response (CR) were observed, for an overall response rate of 15% (95% exact confidence interval, 5.1% to 31.9%). All the responses occurred in the subgroup of 24 platinum-resistant cases, in whom the response rate was 21% (95% exact confidence interval, 7.1% to 42.1%). Seven patients became stabilized on VNLB, and 27% of the cases showed a reduction in serum cancer antigen 125 (CA 125) levels. G3/G4 side effects consisted of neutropenia, anemia, and worsening of preexisting peripheral neuropathy. No treatment-related deaths occurred. CONCLUSION VNLB led to a 21% response rate in the population of heavily pretreated and platinum-resistant ovarian cancer patients. Further studies of VNLB alone or in combination with taxanes are warranted in patients with less pretreatment.

INNOVATE: A phase II study of TTFields (200 kHz) concomitant with weekly paclitaxel for recurrent ovarian cancer—Updated safety and efficacy results.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5580-5580 ◽  
Author(s):  
Ignace Vergote ◽  
Roger von Moos ◽  
Luis Manso ◽  
Cristiana Sessa
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Electric Fields ◽  
Skin Irritation ◽  
Intermediate Frequency ◽  
Weekly Paclitaxel ◽  
Ca 125 ◽  
Serious Adverse Events ◽  
Platinum Resistant

5580 Background: TTFields are a non-invasive, regional antimitotic treatment modality, which have been approved for the treatment of recurrent and newly diagnosed glioblastoma by the FDA. TTFields act by delivering intermediate frequency alternating electric fields to the tumor, predominantly by disrupting the formation of the mitotic spindle during metaphase. INNOVATE was the first trial testing TTFields (200kHz) in ovarian cancer patients. Methods: Thirty-one recurrent, platinum-resistant, unresectable ovarian cancer patients were enrolled in the INNOVATE trial and treated with TTFields in combination with weekly paclitaxel. The primary endpoint was treatment emergent adverse events. Secondary endpoints included progression free-survival, overall survival and radiological response rate. Results: The median age was 60 (range – 45-77), most patients (77%) had serous histology. 52% had an ECOG score of 0. The median number of prior chemotherapy regimens was 4.1 (range 1-11). All patients were platinum-resistant, and 97% of patients received prior taxane-containing regimens. Ten (32%) patients suffered from serious adverse events (SAEs) during the study, none were related to TTFields. Of all reported SAEs, 31% were related to gastrointestinal disorders (ileus, jaundice and ascites) and 31% were respiratory events (dyspnea, pleural effusion and pulmonary embolism). Only one SAE which, related to the tumor, led to permanent discontinuation of the device. Most patients were reported to have mild-moderate, TTFields-related skin irritation, out of whom only two patients (6.4%) had severe-grade events. The median PFS was 8.9 months (95% CI 4.7, NA). Of the evaluable tumors, 25% had partial response and another 46.4% stable disease – a clinical benefit of 71.4%. Six patients (19.4%) had a CA 125 response, translating into a decrease of 50% or more in serum levels. The median OS was not reached. Conclusions: TTFields concomitant to weekly paclitaxel are tolerable and safe in heavily pre-treated platinum-resistant ovarian cancer ovarian cancer patients. These data support further clinical testing of TTFields with chemotherapy in ovarian cancer. Clinical trial information: NCT02244502.

scholarly journals Prediction of tumour response induced by chemotherapy using modelling of CA-125 kinetics in recurrent ovarian cancer patients

2014 ◽  
Vol 110 (6) ◽  
pp. 1517-1524 ◽  
Author(s):  
M Wilbaux ◽  
E Hénin ◽  
A Oza ◽  
O Colomban ◽  
E Pujade-Lauraine ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Tumour Response ◽  
Recurrent Ovarian Cancer ◽  
Ca 125

Phase I/II study to evaluate the optimum dose of pegylated-interferon (PEG INTRON) in patients with platinum-resistant ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16010-16010
Author(s):  
P. T. Soliman ◽  
J. B. Gano ◽  
C. F. Levenback ◽  
J. Kavanagh ◽  
D. M. Gershenson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Performance Status ◽  
Pegylated Interferon ◽  
Recurrent Ovarian Cancer ◽  
Ca 125 ◽  
Optimum Dose ◽  
Weekly Schedule ◽  
Interferon Treatment ◽  
Fallopian Tube Cancer ◽  
Platinum Resistant

16010 Background: Intraperitoneal interferon therapy has been shown to have response rates as high as 45% in patients with recurrent ovarian cancer. Continued exposure has also been associated with the effectiveness of interferon treatment. The purpose of this study was evaluate the optimum dose and toxicity profile of PEG INTRON given subcutaneously (SC) on a weekly schedule to women with platinum-resistant ovarian cancer. Methods: Women with platinum-resistant ovarian, peritoneal, or fallopian tube cancer were eligible. Those whose tumors tested positive for IL-8, bFGF, or VEGF were randomized to three PEG INTRON treatment doses, 1.0, 1.25, or 1.5 micrograms/kg/wk SC for a total of 4 weekly injections per cycle. Re-evaluation for tumor response by imaging, physical exam and CA-125 was performed every 2 -3 cycles (8 - 12 weeks). Up to 12 cycles of treatment was allowed. Treatment was continued until progression of disease or unacceptable toxicity. Results: Thirty patients were enrolled, only 17 received treatment; 11 tested negative, 1 refused testing, 1 tested positive but refused treatment. Median age was 56 years (35–73). Of those treated, 94% (16/17) had a performance status of 0. All were heavily pretreated (3–8 prior chemo regimens). One patient received 9 cycles (1.25 micrograms/kg, total dose = 80 mcg) with stable disease. In the remaining 16 patients, 14 (75%) were taken off study due to disease progression; 3 after completing 2 treatment cycles and 11 after <2 treatment cycles. Four patients (24%) discontinued treatment because of toxicity. Two episodes of grade 4 fatigue were reported. Other grade 3 toxicities included visual changes, pain, anemia, neutropenia, depression, myalgia, and nausea/vomiting. Conclusions: There were no clinical responses to weekly PEG INTRON in this patient population. In addition, the regimen was difficult to tolerate. Further investigation into the dose and delivery of PEG INTRON is needed to determine the safety and efficacy of interferon treatment in patients with reuccurent ovarian cancer. No significant financial relationships to disclose.

Topotecan weekly versus routine 5-day schedule in patients with platinum-resistant ovarian cancer (TOWER): A randomized, two-stage phase-II study of the North-Eastern German Society of Gynaecological Oncology (NOGGO)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5526-5526 ◽  
Author(s):  
J. Sehouli ◽  
G. Oskay-Oezcelik ◽  
D. Stengel ◽  
A. du Bois ◽  
S. Markmann ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Therapeutic Index ◽  
Tumor Stage ◽  
Ca 125 ◽  
Study Endpoint ◽  
Primary Study ◽  
Two Stage ◽  
Platinum Resistant

5526 Background: Optimizing the therapeutic index (that is, maintaining drug effectiveness while reducing toxicity) is a major goal in chemotherapy for platinum-resistant ovarian cancer. Early phase-I/II studies suggest that weekly topotecan (T) might be effective and apparently better tolerated than the established 5-day regimen. As yet, no randomized comparison of both regimes was attempted. To prove the hypothesis of an improved therapeutic index with weekly T, we conducted a randomized, multicenter, two-stage phase-II trial, and herein present the data of the planned interim analysis. Methods: Pts with platinresistent ovarian and fallopian tube cancers or primary peritoneal carcinoma, measurable or assessable disease (GCIG-CA-125 response criteria), were eligible. Pts were randomized to receive either weekly T (d1,8,15/q28d, 4 mg/m2) or T from d1–5/q21d at a dose of 1.25 mg/m2. According to Gehan’s two-stage-design, both arms were handled as independent studies. Overall response rate (CR + PR) was defined as primary study endpoint, secondary endpoints of the interim analysis were toxicity and safety. Results: 28 pts in the weekly and 21 pts in the conventional group, enrolled at 38 centers form the basis of this report. 230 cycles of chemotherapy were evaluated for toxicity analyses. Median age was 61 years (range, 36 - 82 years). Demographic baseline characteristics, including tumor stage and grade were well balanced between treatment arms. There were 2/28 and 5/21 responses in weekly and the conventional arm, respectively (Risk Ratio [RR] 0.30, 95% confidence interval [CI] 0.06 - 1.40, p=0.122). The risk of early treatment termination due to tumor progression (RR 1.39, 95%CI 0.75 - 2.56), haematological (RR 0.20, 95% CI 0.01 - 3.97) or non- hematological toxicities (RR 1.96, 95% CI 0.18 - 20.83) did not differ significantly between groups. The only three events of neutropenic fever occurred in the conventional arm (RR 1.70, 95% CI 0.99 - 1.16). Conclusions: Weekly T is well tolerated and potentially active. The second stage of this study will require additional 46 patients each arm. Complete enrolment is expected to be accomplished in May 2007. No significant financial relationships to disclose.

Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type: The PaLiDo study, a phase II nonrandomized multicenter study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5052-5052 ◽  
Author(s):  
Karina Dahl Steffensen ◽  
Marianne Waldstrøm ◽  
Niels Pallisgaard ◽  
Bente Lund ◽  
Kjell Bergfeldt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Response Rate ◽  
Pegylated Liposomal Doxorubicin ◽  
Ca 125 ◽  
Wild Type ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Dermatologic Toxicity

5052 Background: Ovarian cancer (OC) patients with platinum-resistant recurrent disease have few therapeutic options and the response rates are only 10-20% using non-cross-resistant chemotherapeutic agents. The increasing number of negative trials for OC treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may result in improvement in survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). No previous studies have evaluated the effect of panitumumab in OC based on KRAS mutation status. The main purpose was to investigate the response rate in platinum-resistant, KRAS wild-type OC patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab. Methods: Major eligibility criteria were confirmed stage I-IV primary epithelial ovarian/fallopian/peritoneal cancer patients with progression either during or within 6 months after end of first or second line platinum-based chemotherapy. Only patients with measurable disease by CA125 criteria and with KRAS wild type were eligible. Patients were treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m² day 1, every 4 weeks. Tumor assessment was performed at baseline and at every third cycle according to CA-125 criteria. Results: A total of 46 patients were enrolled by 6 study sites in this multi-institutional phase II trial. Within the population evaluable for response (N=33), there was 8 CA125 responders for an overall response rate of 24.3 %. Progression-free and overall survival in the intention-to-treat population (N=43) was 2.7 months (2.5-3.2 months, 95%CI) and 8.1 months (5.6-11.7 months, 95%CI), respectively. The most common treatment related grade 3 toxicities included skin toxicity (42%), fatigue (19%) and vomiting (12%). Conclusions: The combination of PLD and panitumumab demonstrates efficacy in platinum refractory/resistant patients although the dermatologic toxicity was considerable.

Phase 2 trial of tisotumab vedotin in platinum-resistant ovarian cancer (innovaTV 208).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5602-TPS5602 ◽  
Author(s):  
Haider Mahdi ◽  
Steven Robert Schuster ◽  
David M. O'Malley ◽  
Donna M. McNamara ◽  
Reshma A. Rangwala ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Endpoint ◽  
Human Monoclonal Antibody ◽  
Single Agent ◽  
Ca 125 ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Increased Risk

TPS5602 Background: Ovarian cancer (OC) is the most lethal gynecologic cancer, accounting for ≈185,000 deaths worldwide in 2018. Most patients (pts) initially respond to platinum-based chemotherapy (chemo), but more than 50% of pts recur. Pts who recur in ≤6 months have platinum-resistant OC (PROC), which is associated with poor prognosis. Standard therapy for PROC includes chemo ± bevacizumab (bev). However, many pts receive single-agent chemo, which demonstrates limited response and survival (≈12% ORR, 3-4 mo PFS, ≈12 mo OS). Therefore, there is an urgent need for novel therapeutic strategies. Tissue factor (TF) is a novel oncogenic target expressed in OC. Tisotumab vedotin (TV) is a first-in-class antibody drug conjugate comprising a TF-targeted fully human monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. TV has shown encouraging antitumor activity and a manageable safety profile in PROC in the multicohort phase 1/2 innovaTV 201 study. innovaTV 208 is a multicenter, open-label, phase 2 trial with a safety run-in phase for a dose-dense regimen (DDR) evaluating the efficacy and safety of TV in pts with PROC. Methods: innovaTV 208 will enroll ≈142 adult pts with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer; measurable disease by RECIST v1.1; and ECOG score 0-1. Eligible pts must have received bev-containing treatment for OC. Pts with platinum-refractory disease, increased risk of bleeding, active ocular surface disease, or grade > 1 peripheral neuropathy will be excluded. A safety run-in phase for the DDR will be performed in up to 12 pts who received ≤5 prior treatment regimens for PROC. In the DDR, TV will be given at previously decided lower doses IV 3Q4W for the same dose intensity as the standard 1Q3W dose; the primary endpoint is incidence of DLTs. In phase 2, pts who received ≤1 prior cytotoxic chemo regimen for PROC will be randomized to receive TV administered as IV 1Q3W or as IV 3Q4W, if shown to be tolerable. The primary endpoint for phase 2 is confirmed ORR by RECIST v1.1. Secondary endpoints include DOR, time to response, DCR, CA-125 response rate by GCIG criteria, PFS, OS, pharmacokinetics, and safety. Clinical trial information: NCT03657043.

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