scholarly journals Statistical analysis plan for the Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian, fallopian tube or primary peritoneal cancer (of clear cell, endometrioid and high-grade serous type, and carcinosarcoma) trial (DICE)

Trials ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Consuelo Nóhpal de la Rosa ◽  
Jonathan Krell ◽  
Emily Day ◽  
Aaron Clarke ◽  
Meena Reddi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Standard Treatment ◽  
Progression Free Survival ◽  
Statistical Analysis Plan ◽  
Weekly Paclitaxel ◽  
Free Survival ◽  
Secondary Outcomes ◽  
Eortc Qlq

Abstract Background Treatment for ovarian cancer includes platinum-based chemotherapy, but many women become resistant to chemotherapy, becoming platinum-resistant. Standard of care for these women is weekly paclitaxel chemotherapy, but cancers can often become paclitaxel resistant. TAK228, an investigational dual TORC1/2 inhibitor, is an oral therapy that can be added to standard treatment. The DICE trial is a phase II international multicentre, parallel-group, superiority clinical trial with 1:1, open label randomisation which has the aim of investigating the effectiveness of TAK228 plus weekly paclitaxel. The planned sample size is 124 women (62 per treatment arm) with platinum-resistant ovarian cancer. Objective To outline the planned analyses for DICE in a statistical analysis plan (SAP) before database hard lock and the start of analysis. This ensures that bias is minimised during the analysis phase. Results This SAP provides detailed descriptions of the analysis principles and statistical procedures for analysing primary and secondary outcomes of the trial. The primary outcome is overall progression-free survival (PFS). Secondary outcomes include progression-free survival (PFS) at 24 weeks, overall response rate (ORR), duration of response (DoR), time to progression (TTP), clinical benefit rate (CBR) at 4 months, Cancer Antigen 125 (CA125) response according to Gynaecological Cancer Intergroup (GCIG) criteria, overall survival (OS), safety and tolerability as assessed by adverse events and the quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-OV28). This detailed description includes significance levels, sensitivity analyses and compliance analysis. Discussion The DICE trial will determine whether the addition of TAK228 to weekly paclitaxel chemotherapy shows a statistically significant improvement to participant’s progression free and overall survival and that the adverse events (AEs) and quality of life (QoL) are not significantly worse than the standard treatment. The study commenced recruitment in September 2018. An interim analysis was performed in early 2021, the results of which advised continuation of the trial. The study recruitment is ongoing and is due to complete by the end of 2021. Trial registration ClinicalTrials.govNCT03648489. Registered on 27 August 2018

DICE: Study Protocol for a Randomised Trial Investigating a Novel Therapy Called TAK228 in Ovarian Cancer Resistant to Standard Treatment

2021 ◽  
Author(s):  
Lee Webber ◽  
Francesca Fiorentino ◽  
Jonathan Krell ◽  
Consuelo Nohpal de la Rosa
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Adverse Events ◽  
Standard Treatment ◽  
Phase Iii ◽  
Response To Treatment ◽  
Weekly Paclitaxel ◽  
Novel Therapy ◽  
Platinum Based Chemotherapy

Abstract Background:The standard initial treatment for ovarian cancer is surgery and platinum-based chemotherapy and potentially maintenance therapy with avastin or inhibitors of poly-ADP ribose polymerase (PARP). While a proportion of women are cured by this approach, the vast majority will relapse and become resistant to platinum chemotherapy either initially or on subsequent treatment. There is an unmet need to improve response to treatment and quality of life in these women. TAK228 is a novel therapy that can be added to standard treatment in the participant population and the aim of the DICE trial is to assess its effectiveness. Laboratory and clinical research has shown that these ovarian cancers may respond to the molecular target of a drug such as TAK228, and there have been studies using it in other advanced solid tumours including endometrial cancer. Methods: 124 eligible women will be recruited from participating research sites in the United Kingdom (UK) and Germany. Randomised participants will receive either weekly paclitaxel alone (standard treatment, n=62) or TAK228 plus weekly paclitaxel (n=62) until the cancer significantly worsens, there are significant adverse events or any other protocol-defined stopping criteria. Participants will be monitored for response to treatment (using radiological imaging), adverse events and quality of life during both randomised treatment and subsequent follow up.Discussion:The primary objective/endpoint of the study is to compare the two treatments in terms of progression free survival, or the length of time that each participant is alive without the cancer significantly worsening according to defined assessment criteria. If the addition of TAK228 to weekly paclitaxel chemotherapy is shown to significantly improve this statistically, and adverse events and quality of life are not significantly worse than standard treatment, then TAK228 plus weekly paclitaxel could potentially be taken forward within the context of a larger phase III trial.Trial registration:ClinicalTrials.gov NCT03648489. Registered 27th August 2018.https://clinicaltrials.gov/ct2/show/NCT03648489

Nonplatinum Topotecan Combinations Versus Topotecan Alone for Recurrent Ovarian Cancer: Results of a Phase III Study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group

2008 ◽  
Vol 26 (19) ◽  
pp. 3176-3182 ◽  
Author(s):  
Jalid Sehouli ◽  
Dirk Stengel ◽  
Guelten Oskay-Oezcelik ◽  
Alain G. Zeimet ◽  
Harald Sommer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Refractory

PurposeThe management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine.Patients and MethodsWomen with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m2/d, topotecan 1.0 mg/m2plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m2/d plus gemcitabine 800 mg/m2on day 1 and 600 mg/m2on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire).ResultsThe trial enrolled 502 patients with a mean age of 60.5 years (± 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia.ConclusionNonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.

Randomized Study of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group Comparing Quality of Life in Patients With Ovarian Cancer Treated With Cisplatin/Paclitaxel Versus Carboplatin/Paclitaxel

2006 ◽  
Vol 24 (4) ◽  
pp. 579-586 ◽  
Author(s):  
Elfriede R. Greimel ◽  
Vesna Bjelic-Radisic ◽  
Jacobus Pfisterer ◽  
Felix Hilpert ◽  
Fedor Daghofer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Response To Treatment ◽  
Free Survival ◽  
The Impact

Purpose The objective of this study was to compare the quality of life (QoL) of ovarian cancer patients treated with paclitaxel/carboplatin (TC) versus paclitaxel/cisplatin (PT) and to determine the impact of treatment toxicity on the various QoL domains. Patients and Methods In this phase III trial, 798 patients with ovarian cancer stages IIB-IV were randomly assigned to receive TC or PT. The primary end point was progression-free survival; secondary end points included toxicity, QoL, and response to treatment. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 before treatment, within 3 days before the second and the fourth chemotherapy cycle, and 3 weeks after completion of chemotherapy. Results Previously reported data showed that patients undergoing TC or PT did not differ in progression-free survival and overall survival. However, the TC arm was superior, indicating a better overall QoL compared with the PT arm. Controlling for toxicity and age, a significant treatment by assessment time interaction was found for four QoL functioning scales and three symptoms scales. Patients in the TC arm showed better means scores after treatment on overall QoL (P = .012), physical functioning (P = .012), role functioning (P = .005), and cognitive functioning (P = .024), compared with the PT arm. Concerning symptom experience, patients undergoing TC showed less nausea and vomiting (P < .001), less appetite loss (P < .001), and less fatigue (P = .033) after completion of treatment compared with patients undergoing PT. Conclusion The TC regimen achieved better QoL outcomes compared with the PT regimen. Thus, clinicians may consider replacing cisplatin with carboplatin when treating ovarian cancer patients with chemotherapy.

scholarly journals Safety and Efficacy of Weekly Paclitaxel and Cisplatin Chemotherapy for Ovarian Cancer Patients with Hypersensitivity to Carboplatin

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 640
Author(s):  
Shinichi Tate ◽  
Kyoko Nishikimi ◽  
Ayumu Matsuoka ◽  
Satoyo Otsuka ◽  
Makio Shozu
Keyword(s):  
Ovarian Cancer ◽  
Progressive Disease ◽  
Renal Toxicity ◽  
Progression Free Survival ◽  
Median Number ◽  
Weekly Paclitaxel ◽  
Peritoneal Carcinoma ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Carboplatin Hypersensitivity

Background: This study aimed to evaluate the safety and efficacy of weekly paclitaxel and cisplatin chemotherapy (wTP) in patients with ovarian cancer who developed carboplatin hypersensitivity reaction (HSR). Methods: We retrospectively investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed carboplatin HSR during previous chemotherapy (carboplatin and paclitaxel) at our institution between 2011 and 2019. After premedication was administered, paclitaxel was administered over 1 h, followed by cisplatin over 1 h (paclitaxel 80 mg/m2; cisplatin 25 mg/m2; 1, 8, 15 day/4 weeks). We investigated the incidence of patients who successfully received wTP for at least one cycle, treatments compliance, progression-free survival (PFS), and overall survival (OS). Results: The median number of wTP administration cycles was 4 (Interquartile Range IQR, 3–7), 71 patients (83%) successfully received wTP, and 15 patients (17%) developed cisplatin HSR. The efficacy of treatment was as follows: 55 (64%) patients completed the scheduled wTP, 9 (10%) patients discontinued due to HSR to cisplatin within 6 cycles, 1 (1%) patient discontinued due to renal toxicity (grade 2) at the 6th cycle, and 21 (24%) patients discontinued due to progressive disease within 6 cycles. The median PFS and OS after administration of wTP were 10.9 months (95% CI: 7.7–17.7) and 25.9 months (95% CI: 19.0–50.2), respectively. Conclusions: wTP was safe and well-tolerated in patients who developed carboplatin HSR.

Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer

2011 ◽  
Vol 121 (2) ◽  
pp. 269-272 ◽  
Author(s):  
David M. O'Malley ◽  
Debra L. Richardson ◽  
Patrick S. Rheaume ◽  
Ritu Salani ◽  
Eric L. Eisenhauer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Progression Free Survival ◽  
Weekly Paclitaxel ◽  
Free Survival ◽  
Heavily Pretreated

scholarly journals Quality of life among ovarian cancer survivors in Haji Adam Malik General Hospital Medan, Indonesia

2020 ◽  
Vol 11 (2) ◽  
pp. 133-139
Author(s):  
Kristivani Br Ginting ◽  
Muhammad Rizki Yaznil ◽  
M. Oky Prabudi ◽  
Lili Rahmawati
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Cancer Survivors ◽  
General Hospital ◽  
Detection Methods ◽  
Cross Sectional ◽  
Eortc Qlq C30 ◽  
C 30 ◽  
Eortc Qlq

Latar belakang: Kanker ovarium memiliki angka mortalitas yang cukup tinggi dikarenakan gejalanya yang tidak spesifik, sering ditemukan pada stadium lanjut, dan belum adanya metode deteksi dini yang sudah terbukti. Untuk menilai keberhasilan terapi penyintas kanker ovarium, tidak hanya dinilai dari aspek klinis tetapi juga dinilai dari kualitas hidup penyintas kanker ovarium yang penilaiannya berdasarkan skala fungsional dan skala gejala dalam kuesioner EORTC QLQ C30 dan EORTC QLQ OV28. Metode: Penelitian ini menggunakan desain penelitian cross sectional, menggunakan data primer dari hasil wawancara dengan kuesioner EORTC QLQ C30 dan EORTC QLQ OV28 serta data sekunder yang berasal dari rekam medik di RSUP Haji Adam Malik Medan tahun 2017 - 2018. Sampel penelitian dipilih dengan metode total sampling dari seluruh data rekam medik yang memenuhi kriteria penelitian.   Hasil: Hasil penelitian ini didapatkan kualitas hidup global penyintas kanker ovarium 89.36% adalah baik, dan 10.64% adalah sedang serta tidak ada yang memiliki kualitas hidup buruk. Namun, didapatkan adanya gangguan pada skala fungsional berupa: fungsi emosional, fungsi kognitif, fungsi seksual, dan sikap terhadap penyakit, serta adanya permasalahan pada skala gejala berupa: kelelahan, nyeri, neuropati perifer, dan gejala menopause. Didapatkan juga tidak ada hubungan karakteristik usia, jenis histopatologis, stadium, lama terapi dengan kualitas hidup penyintas kanker ovarium, namun terdapat hubungan antara jenis terapi dengan kualitas hidup penyintas kanker ovarium. Kesimpulan: Kualitas hidup penyintas kanker ovarium secara global adalah baik. Kata Kunci: Kualitas Hidup, Penyintas Kanker Ovarium, EORTC QLQ C-30, EORTC QLQ     OV-28   Abstract Background: Ovarian cancer has a high mortality rate due to nonspecific symptoms, often found at an advanced stage, and also the absence of proven early detection methods. To assess the success of ovarian cancer survivors therapy, it is not only assessed from the clinical aspect but also from the quality of life of ovarian cancer survivors which is based on the functional and symptom scale in the EORTC QLQ C30 and EORTC QLQ OV28 questionnaires.  Methods: This study used a cross-sectional study design, using primary data from interviews with the survivors based on the questionnaire EORTC QLQ C30 and EORTC QLQ OV28 as well as secondary data derived from medical records at Haji Adam Malik General Hospital Medan in 2017 - 2018. The research sample was used with a total sampling method from all medical record data that fulfill the research criteria.  Result: The quality of life of ovarian cancer survivors is generally good (89.36%), meanwhile the rest is moderate (10.64%) without the poor quality of life. However, there are disorders on the functional scale in the form of emotional function, cognitive function, sexual function, and attitude toward disease. Likewise on the scale of symptoms, there are problems including: fatigue, pain, peripheral neuropathy, and menopausal symptoms.  Conclusion: The quality of life of ovarian cancer survivors globally is good. Keywords: Quality of Life, Ovarian Cancer Survivors, EORTC QLQ C-30, EORTC QLQ OV-28  

Validation of the Polish version of the EORTC QLQ-OV28 module for the assessment of health-related quality of life in women with ovarian cancer

2013 ◽  
Vol 14 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Jan Paradowski ◽  
Krzysztof A Tomaszewski ◽  
Krzysztof Bereza ◽  
Iwona M Tomaszewska ◽  
Artur Pasternak ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Health Related Quality ◽  
Polish Version ◽  
Related Quality ◽  
Health Related ◽  
Eortc Qlq
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