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

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

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.

Clinical efficacy and safety of early adjuvant chemotherapy for stage III colon cancer: Short-term outcomes of a multicenter, randomized, open-label, phase 3 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3598-3598
Author(s):  
Jun Seok Park ◽  
Soo Yeun Park ◽  
Gyu-Seog Choi ◽  
Hye Jin Kim ◽  
Jong Gwang Kim ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adverse Events ◽  
Surgical Complication ◽  
Phase Iii ◽  
Stage Iii ◽  
Survival Outcomes ◽  
Stage Iii Colon Cancer

3598 Background: Adjuvant chemotherapy (AC) is recommended to commence within 8 weeks since after surgical resection of stage II or III colon cancer. Results of many retrospective studies showed inferior survival outcomes following delay of AC delay. Moreover, preclinical studies showed that the progression of disseminated cancer cells is profound during the postoperative period. This study is the first prospective trial to evaluate early (≤ 14 days postoperative) AC for patients (pts) with stage III colon cancer. Methods: This study is a prospective, multicenter, randomized phase III trial. Pts with pathological stage III colon cancer were enrolled and randomized 1:1 to early AC (starting AC ≤ 14 days after surgery) or conventional AC (starting AC > 14 days after surgery). Pts were recommended to receive 12 cycles of FOLFOX-6 for AC. The primary endpoint was disease-free survival. The secondary endpoints were overall survival, adverse events, surgical complication during AC, and patient-reported outcomes (quality of life) during 1 year after surgery. Herein, safety data, chemotherapy delivery, and quality of life are presented. Results: This study randomized 443 pts either early AC arm (221pts) or early AC arm (222 pts) to the during September 2011 to March 2020. 380 pts who received at least one cycle of FOLFOX-6 were included in the safety analysis (192 and 188 in the early and conventional AC arms, respectively). The baseline characteristics of the two groups were well-balanced except for the interval from the surgery to the initial AC. The early and conventional AC arms started their first chemotherapy at median of 13 (4-43 days) and 29 (17-53 days) after surgery (p < 0.001), respectively. No significant differences were seen in the median chemotherapy cycles, AC completion, and relative oxaliplatin dose intensity between groups. AC Completion without any change of dose or schedule delay was seen in 18% and 20% in early and conventional AC arms respectively, while dose reduction or delay was 65% and 61%, respectively. Toxicities of grade 3 or more were seen in 28% in both groups. One patient in the early AC arm underwent an emergent operation for anastomotic leakage on the second day of 5-fluorouracil infusion (postoperative day 14). However, the surgical complication was not seen in any other patient. The scores of the European Organization for Research and Treatment of Cancer Quality of Life core 30 questionnaire were similar in both arms at baseline (before starting AC), and 1 month, 3 months, 6 months, and 12 months after surgery. Conclusions: Early AC was safe and did not increase either chemotherapy-related adverse events or surgery-related complications during treatment. Moreover early AC did not reduce the quality of life of the pts during 1 year after surgery. This study continues to follow-up the patients for survival outcomes. Clinical trial information: NCT01460589.

Does tetracycline prevent/palliate epidermal growth factor receptor (EGFR) inhibitor-induced rash? A phase III trial from the North Central Cancer Treatment Group (N03CB)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA9006-LBA9006 ◽  
Author(s):  
A. Jatoi ◽  
K. Rowland ◽  
J. A. Sloan ◽  
H. M. Gross ◽  
P. A. Fishkin ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Adverse Events ◽  
Controlled Trial ◽  
Skin Irritation ◽  
Drop Out ◽  
Phase Iii ◽  
Type I ◽  
Life Questionnaire ◽  
Egfr Inhibitor

LBA9006 Purpose: Many patients who receive EGFR inhibitors develop an acneiform rash, and anecdotal reports suggest tetracycline is effective in treating it. To our knowledge, however, no rigorous trials have ever been published to substantiate this approach. This double- blinded, placebo-controlled trial was conducted to assess the role of tetracycline in preventing EGFR inhibitor-induced rash and/or reducing its severity. Methods: 61 patients were randomly assigned to tetracycline 500 mg orally twice a day×4 weeks versus an identical, similarly prescribed placebo. Eligibility criteria required all patients to have begun an EGFR inhibitor </= 7 days prior with no rash at study entry. Patients were to be followed for 8 weeks. Physician assessments of rash incidence, severity, and adverse events, occurred at 4 and 8 weeks. Patients completed a weekly rash diary, quality of life questionnaire (SKINDEX-16), and EGFR inhibitor compliance questionnaire. Thirty patients per group provides 90% power to detect a difference in rash incidence (the primary endpoint) of 40% between groups and of rejecting the null hypothesis of equal proportions with a type I error of 5% (2-sided). Results: Treatment arms were balanced on baseline characteristics, drop out rates, and rates of discontinuation of the EGFR inhibitor. Rash incidence was comparable across arms. Physicians reported that 16 tetracycline-treated patients (70%) and 22 placebo-exposed patients (76%) developed a rash (p=0.61). However, tetracycline appears to have lessened rash severity. By week 4, physician-reported grade 2 rash occurred in 17% of tetracycline-treated patients (n=4) and 55% of placebo- exposed patients (n=16); (p=0.04). Tetracycline-treated patients reported better scores on certain quality of life parameters (SKINDEX-16), such as skin burning or stinging, skin irritation, and being bothered by a persistence/recurrence of a skin condition. Adverse events were comparable across arms. Conclusion: Tetracycline did not prevent EGFR inhibitor-induced rashes. However, diminished rash severity and improved quality of life suggest this antibiotic merits further study. No significant financial relationships to disclose.

Health-related quality of life/patient-reported outcomes in relapsed ovarian cancer: Results from a randomized phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD alone

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5526-5526
Author(s):  
C. N. Krasner ◽  
A. Poveda ◽  
T. Herzog ◽  
J. Vermorken ◽  
B. Monk ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Health Status ◽  
Patient Reported Outcomes ◽  
Phase Iii ◽  
Gi Symptoms ◽  
Patient Reported ◽  
Phase Iii Study ◽  
The Impact

5526 Background: In an open-label, multicenter, randomized phase III study comparing the combination of trabectedin and PLD to PLD alone in patients with relapsed ovarian cancer, the combination demonstrated significantly improved progression free survival and response rates, manageable non-cumulative toxicity, and fewer PLD-associated adverse events. We studied the impact of the combination of trabectedin with PLD on the quality of life (QoL)/patient-reported outcomes (PRO) evaluated as part of the trial. Methods: QoL/PRO questionnaires, EORTC-QLQ C30, OV28, and EQ-5D were completed by patients at screening and on Day 1 of every other treatment cycle starting with Cycle 1, and at the end-of-treatment visit. Global health status/QoL, fatigue, rain subscales from QLQ C30, and abdominal pain/GI symptoms scale from OV28 were chosen a priori for primary analyses. Other scales of the three questionnaires were analyzed on a supportive basis. Results: A total of 672 patients were randomized. 663 (98%) completed at least the baseline questionnaires. Median cycles of treatment was 6 (131 days) for the combination arm and 5 (143 days) for the monotherapy arm. Mixed effects models (using a covariance structure of AR[1]) predicting the score at baseline and follow-up scores as a function of treatment, days after baseline, and interaction between treatment and days after baseline showed no significant differences between the treatment arms for any of the prespecified scales. Similar analyses of other scales, including EQ-5D Health Index scores and Health State on the Visual Analog Scale, support the findings. Conclusions: The addition of trabectedin to PLD results in superior efficacy in patients with relapsed ovarian cancer, with no added decrement to overall health status as assessed by PRO. [Table: see text]

When will I feel normal again? Quality of life trajectories after first-line chemotherapy for ovarian cancer.

2018 ◽  
Vol 36 (7_suppl) ◽  
pp. 172-172
Author(s):  
Penelope M Webb ◽  
Vanessa Beesley ◽  
Christina Nagle ◽  
Peter T. Grant ◽  
Anna deFazio ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
General Population ◽  
Primary Treatment ◽  
Cancer Prognosis ◽  
Life Trajectories ◽  
Platinum Based Chemotherapy ◽  
Ovarian Cancer Prognosis ◽  
Over Time

172 Background: Patients often ask if/when they will feel normal again following treatment for ovarian cancer (OC). There is a paucity of data on the trajectories of quality of life (QoL), physical (PWB), social (SWB), emotional (EWB) and functional (FWB) wellbeing over time following chemotherapy and especially regarding those who have persistent problems. Our aim was to quantify the proportion of women with significantly lower QoL/wellbeing than the general population at the end of treatment and determine if/when they return to normal. Methods: The OPAL (Ovarian cancer Prognosis & Lifestyle) Study is a prospective study of Australian women diagnosed with invasive OC from 2012-15 who agreed to complete regular questionnaires after diagnosis. 580 participants who received ≥3 cycles of platinum-based chemotherapy as primary treatment and completed a questionnaire while on or < 6 weeks after completing chemotherapy (baseline) were included. FACT-G data came from questionnaires at baseline and ~3, 6, 9 & 18 months post-baseline. Group-based trajectory models were used to identify groups with distinct patterns of QoL/wellbeing over time. Results: Overall, 44% (254) of women had QoL scores significantly lower than the general population at baseline; 35% (88) returned to normal by 3 months after treatment, 73% by 6 months and 27% (69) had not returned to normal by 18 months. The Table shows the comparable figures for the wellbeing subscales. Conclusions: While > 50% of women with OC can expect similar QoL, FWB and EWB to the general population at the end of chemotherapy, PWB was compromised in 3 of 4 women. For most, wellbeing recovered within 6 months but a substantial proportion reported ongoing deficits. A particularly prolonged impact was seen for those with poor EWB at baseline, warranting early intervention in this subset. [Table: see text]

Quality of Life and Adverse Events: Prognostic Relationships in Long-Term Ovarian Cancer Survival

2021 ◽  
Author(s):  
Lari Wenzel ◽  
Kathryn Osann ◽  
Chelsea McKinney ◽  
David Cella ◽  
Giulia Fulci ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Adverse Events ◽  
Cancer Survival ◽  
Short Term ◽  
Term Survival ◽  
Point Increase ◽  
Ovarian Cancer Survival

Abstract BACKGROUND There is a critical need to identify patient characteristics associated with long-term ovarian cancer survival. METHODS Quality of life (QOL), measured by the Functional Assessment of Cancer Therapy-Ovarian-Trial Outcome Index (FACT-O-TOI), including physical, functional and ovarian-specific subscales, was compared between long-term (LTS) (8+ years) and short-term (STS) (&lt;5 years) survivors of GOG 218 at baseline, before cycles 4, 7, 13, 21, and 6 months post-treatment using linear and longitudinal mixed models adjusted for covariates. Adverse events (AEs) were compared between survivor groups at each assessment using generalized linear models. All p-values are two-sided. RESULTS QOL differed statistically significantly between STS (N = 1115) and LTS (N = 260) (p &lt; .001). Baseline FACT-O-TOI and FACT-O-TOI change were independently associated with long-term survival (OR = 1.05, 95% CI = 1.03–1.06 and OR = 1.06, 95% CI = 1.05–1.07, respectively). A 7-point increase in baseline QOL was associated with a 38.0% increase in probability of LTS, while a 9-point increase in QOL change was associated with a 67.0% increase in odds for LTS. QOL decreased statistically significantly with increasing AE quartiles (cycle 4 quartiles: 0–5 v. 6–8 v. 9–11 v. ≥12 AEs, p = .01; cycle 21 quartiles: 0–2 v. 3 v. 4–5 v. ≥6 AEs, p = .001). Further, LTS reported statistically significantly better QOL compared to STS (p = .03 and p = .01, cycles 4 and 21, respectively), with similar findings across higher AE grades. CONCLUSION Baseline and longitudinal QOL change scores distinguished long versus short-term survivors and are robust prognosticators for long term survival. Results have trial design and supportive care implications, providing meaningful prognostic value in this understudied population.

scholarly journals Assessment of Quality of Life in Advanced Non-Small Cell Lung Cancer Patients on Platinum-Based Chemotherapy Combinations

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S A Abdelwahab ◽  
A S Tawfik ◽  
N A Mosalam ◽  
E M E Ghazy
Keyword(s):  
Quality Of Life ◽  
Lung Cancer ◽  
Advanced Nsclc ◽  
Response To Treatment ◽  
Health Related Quality ◽  
Platinum Based Chemotherapy ◽  
Related Quality ◽  
Health Related ◽  
Eortc Qlq

Abstract Background Lung cancer is the most commonly diagnosed cancer worldwide for both sexes. There are 1.8 million new cases in 2012 (12.9% of the total), 58% of which occurred in the less developed regions. The disease remains the most common cancer in men worldwide (1.2 million, 16.7% of the total) and the most common causes of cancer deaths worldwide for both sexes, estimated to be responsible for nearly one in five (1.59 million deaths, 19.4% of the total) Aim of the Work are to evaluate the effect of platinum-based chemotherapy combinations as a first line treatment on health related quality of life (HRQOL) in advanced NSCLC Egyptian patients and to assess tumor’s response to treatment and treatment toxicity. Patients and Methods A prospective, single arm clinical study, to evaluate the effect of palliative chemotherapy on advanced NSCLC patient’s health related quality of life before starting chemotherapy and after 3 cycles of treatment, patient’s response to treatment and toxicity related to treatment. Results 61 patients completed the EORTC QLQ-C30 and the QLQ-LC13 for the evaluation of HRQoL before the 1st cycle of chemotherapy. Started with 70 patients, 9 were excluded during the study (because of a change in the chemotherapy protocol or because of treatment discontinuation during the following cycles of chemotherapy. Conclusion The present study explored self-reported quality of life in advanced NSCLC patients receiving chemotherapy, Aiming for a better understanding of how chemotherapy influences HRQoL. The importance of patient perception of their own health regarding the complexity of cancer, which is a disease that affects every dimension of life and the way in which individuals perceive the environment, the diagnosis, and the therapy. Therefore, the combination of periodic quality of life assessments and clinical practice should be more extensively.

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