The MITO8 phase III international multicenter randomized study testing the effect on survival of prolonging platinum-free interval (PFI) in patients with ovarian cancer (OC) recurring between 6 and 12 months after previous platinum-based chemotherapy: A collaboration of MITO, MANGO, AGO, BGOG, ENGOT, and GCIG.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5505-5505 ◽  
Author(s):  
Sandro Pignata ◽  
Giovanni Scambia ◽  
Francesco Raspagliesi ◽  
Viviana Murgia ◽  
Carmela Pisano ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Randomized Study ◽  
Phase Iii ◽  
Free Interval ◽  
Platinum Based Chemotherapy ◽  
International Multicenter

scholarly journals Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer – a randomized phase III trial (AGO-OVAR 2.29/ENGOT-ov34)

2020 ◽  
Vol 30 (12) ◽  
pp. 1997-2001 ◽  
Author(s):  
Philipp Harter ◽  
Patricia Pautier ◽  
Els Van Nieuwenhuysen ◽  
Alexander Reuss ◽  
Andres Redondo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
De Novo ◽  
Checkpoint Inhibitors ◽  
Tissue Sample ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Exclusion Criteria ◽  
Free Interval ◽  
Platinum Based Chemotherapy

BackgroundImprovement in clinical outcomes of patients with platinum-resistant disease is an unmet medical need and trials in this population are urgently needed. Checkpoint-inhibitors have already shown activity in multiple other tumor entities and ovarian cancer, especially in the combination with anti-angiogenic treatment.Primary objectiveTo test if the activity of non-platinum-based chemotherapy and bevacizumab could be improved by the addition of atezolizumab.Study hypothesisThe addition of atezolizumab to standard non-platinum combination of chemotherapy and bevacizumab improves median overall survival from 15 to 20 months.Trial designPatients are randomized to chemotherapy (paclitaxel weekly or pegylated liposomal doxorubicin) + bevacizumab + placebo vs chemotherapy + bevacizumab + atezolizumab. Stratification factors are: number of prior lines, planned type of chemotherapy, prior use of bevacizumab, and tumor programmed death-ligand 1 (PD-L1) status.Major inclusion/exclusion criteriaRecurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer with up to three prior therapies and a treatment-free interval after platinum of less than 6 months. Patients with three prior lines of chemotherapy are eligible irrespective of the platinum free-interval. A de novo tumor tissue sample biopsy for determination of PD-L1 status prior to randomization for stratification is mandatory. Major exclusion criteria consider bevacizumab-specific and immunotherapy-specific criteria.Primary endpointOverall survival and progression-free survival are co-primary endpoints.Sample sizeIt is planned to randomize 664 patients.Trial registrationNCT03353831.

Phase II trial of paclitaxel in patients with progressive ovarian carcinoma after platinum-based chemotherapy: a Gynecologic Oncology Group study.

1994 ◽  
Vol 12 (9) ◽  
pp. 1748-1753 ◽  
Author(s):  
J T Thigpen ◽  
J A Blessing ◽  
H Ball ◽  
S J Hummel ◽  
R J Barrett
Keyword(s):  
Ovarian Carcinoma ◽  
Salvage Therapy ◽  
Gynecologic Oncology ◽  
Active Agent ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Severe Toxicity ◽  
Oncology Group ◽  
Free Interval ◽  
Platinum Based Chemotherapy

PURPOSE This Gynecologic Oncology Group (GOG) trial of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) as salvage therapy for recurrent epithelial carcinoma of the ovary sought to confirm activity reported previously. If positive, the trial was to serve as a basis for phase III trials of Taxol in combination with platinum compounds in first-line therapy. PATIENTS AND METHODS Patients with recurrent, persistent, or progressive ovarian carcinoma during or after platinum-based chemotherapy received Taxol 170 mg/m2 intravenously once over 24 hours every 3 weeks. All patients had measurable disease and received premedication (dexamethasone, diphenhydramine, and ranitidine) followed by Taxol. RESULTS Of 49 patients, 45 were eligible and assessable. Among 43 patients who were assessable for response, there were eight complete and eight partial responses (37%). The median progression-free interval was 4.2 months, and median survival 16 months. Among 27 resistant patients who progressed during or within 6 months of prior platinum-based therapy or had stable disease as the best response, five complete (18%) and four partial (15%) responses were observed (33%). The median progression-free interval was 4 months. Among 16 sensitive patients who responded and progressed more than 6 months after prior platinum-based treatment, three complete (19%) and four partial (25%) responses were observed (44%). The median progression-free interval was 4.9 months. Grade 4 neutropenia (< 500/microL), the most frequent and severe toxicity, occurred in 73% of patients. Other hematologic effects were less frequent and less severe. Cardiac problems and hypersensitivity reactions were observed in one patient each. CONCLUSION Taxol is a highly active agent in ovarian carcinoma, even in patients who are clinically resistant to platinum-based chemotherapy, and produces frequent and severe, albeit manageable, myelosuppression. It is clearly active as salvage therapy for ovarian carcinoma.

CONTACT-01: A phase III, randomized study of atezolizumab plus cabozantinib versus docetaxel in patients with metastatic non-small cell lung cancer (mNSCLC) previously treated with PD-L1/PD-1 inhibitors and platinum-containing chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS9134-TPS9134
Author(s):  
Joel W. Neal ◽  
Palak Kundu ◽  
Tomohiro Tanaka ◽  
Ida Enquist ◽  
Sid Patel ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Randomized Study ◽  
Phase Iii ◽  
Clinical Activity ◽  
Open Label ◽  
Eligibility Criteria ◽  
Recist 1.1 ◽  
Platinum Based Chemotherapy ◽  
Patient Reported ◽  
Previously Treated

TPS9134 Background: Patients with mNSCLC who progress on anti–PD-L1/PD-1 therapy administered in combination with or after platinum-based chemotherapy (PBC) are mainly treated with docetaxel or pemetrexed monotherapy. These therapies only have modest clinical activity, leaving a high unmet medical need. Cabozantinib, a tyrosine kinase inhibitor (TKI), promotes an immune-permissive environment and may enhance the efficacy of PD-L1/PD-1 inhibitors, offering a promising second/third-line therapeutic opportunity for patients with mNSCLC. In a Phase Ib multi-cohort study (COSMIC-021; NCT03170960), cabozantinib plus atezolizumab (anti–PD-L1) showed an acceptable safety profile and promising efficacy (ORR: 27%; mDOR: 5.7 mo [range: 2.6-6.9]; disease control rate [CR + PR + SD]: 83%) in 30 patients with mNSCLC who had progressed after prior anti–PD-L1/PD-1 therapy plus chemotherapy (Neal et al. J Clin Oncol 2020). The Phase III CONTACT-01 study will further evaluate the efficacy and safety of atezolizumab plus cabozantinib versus docetaxel monotherapy in patients with mNSCLC who have progressed during or after prior treatment with anti–PD-L1/PD-1 therapy and PBC. Methods: CONTACT-01 (NCT04471428) is a Phase III, multi-center, randomized, open-label study that will enroll ≈350 patients from 150 to 200 sites internationally. Key eligibility criteria include histologically or cytologically confirmed mNSCLC, disease progression with concurrent or sequential anti–PD-L1/PD-1 treatment and PBC, measurable disease (RECIST 1.1), ECOG PS of 0-1 and the availability of tissue specimens for centralized PD-L1 testing or known PD-L1 status using a health authority–approved PD-L1 assay. Patients with NSCLC previously treated with cabozantinib, docetaxel or anti–PD-L1/PD-1 + VEGFR TKIs are excluded. Patients with known sensitizing EGFR/ALK mutations and active or untreated CNS metastases are also excluded. Patients will be randomized 1:1 to receive either atezolizumab (1200 mg IV every 3 weeks) + cabozantinib (40 mg orally once daily) or docetaxel (75 mg/m2 IV every 3 weeks). The primary endpoint is OS. Secondary endpoints include investigator-assessed PFS, ORR and DOR per RECIST 1.1; TTD in patient-reported physical function and global health status (EORTC QLQ-C30); investigator-assessed PFS rates at 6 months and 1 year; OS rates at 1 and 2 years; safety and PK. Clinical trial information: NCT04471428.

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

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