scholarly journals CALLA: Efficacy and safety of concurrent and adjuvant durvalumab with chemoradiotherapy versus chemoradiotherapy alone in women with locally advanced cervical cancer: a phase III, randomized, double-blind, multicenter study

2020 ◽  
Vol 30 (7) ◽  
pp. 1065-1070
Author(s):  
Jyoti Mayadev ◽  
Ana T Nunes ◽  
Mary Li ◽  
Michelle Marcovitz ◽  
Mark C Lanasa ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Cervical Cancer ◽  
Double Blind ◽  
Locally Advanced Cervical Cancer ◽  
To Receive

BackgroundConcurrent chemoradiotherapy is the standard of care for locally advanced cervical cancer. Concurrent chemoradiotherapy with programmed blockade of the cell death-1/programmed cell death-ligand 1 pathway may promote a more immunogenic environment through increased phagocytosis, cell death, and antigen presentation, leading to enhanced immune-mediated tumor surveillance.Primary ObjectiveThe CALLA trial is designed to determine the efficacy and safety of the programmed cell death-ligand 1 blocking antibody, durvalumab, with and following concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in women with locally advanced cervical cancer.Study HypothesisDurvalumab concurrent with and following concurrent chemoradiotherapy will improve progression-free survival in patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 to IVA cervical cancer compared with concurrent chemoradiotherapy alone.Trial DesignCALLA is a phase III, randomized, multicenter, international, double-blind, placebo-controlled study. Patients will be randomized 1:1 to receive either durvalumab (1500 mg intravenously (IV)) or placebo every 4 weeks for 24 cycles. All patients will receive external beam radiotherapy with cisplatin (40 mg/m2) IV or carboplatin (area under the curve 2) IV once a week for 5 weeks, followed by image-guided brachytherapy.Major Inclusion/Exclusion CriteriaThe study will enroll immunotherapy-naïve adult patients with histologically confirmed cervical adenocarcinoma, cervical squamous, or adenosquamous carcinoma FIGO 2009 stages IB2–IIB node positive and stage IIIA–IVA with any node stage. Patients will have had no prior definitive surgical, radiation, or systemic therapy for cervical cancer.Primary EndpointThe primary endpoint is progression-free survival (assessed by the investigator according to Response Evaluation Criteria in Solid Tumors v1.1, histopathological confirmation of local tumor progression or death).Sample SizeApproximately 714 patients will be randomized 1:1 to receive either durvalumab + concurrent chemoradiotherapy or placebo + concurrent chemoradiotherapy.Estimated Dates for Completing Accrual and Presenting ResultsPatient enrollment is continuing globally with an estimated completion date of April 2024.Trial RegistrationNCT03830866.

A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: Preliminary results

2007 ◽  
Vol 104 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Vutisiri Veerasarn ◽  
Vicharn Lorvidhaya ◽  
Pimkhuan Kamnerdsupaphon ◽  
Nan Suntornpong ◽  
Supatra Sangruchi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Advanced Cervical Cancer ◽  
Phase Iii Trial ◽  
Preliminary Results ◽  
Locally Advanced Cervical Cancer

ENGOT-cx11/KEYNOTE-A18: A phase III, randomized, double-blind study of pembrolizumab with chemoradiotherapy in patients with high-risk locally advanced cervical cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6096-TPS6096
Author(s):  
Domenica Lorusso ◽  
Nicoletta Colombo ◽  
Robert L. Coleman ◽  
Leslie M. Randall ◽  
Linda R. Duska ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind Study ◽  
Advanced Cervical Cancer ◽  
Double Blind ◽  
Locally Advanced Cervical Cancer

TPS6096 Background: High-risk locally advanced cervical cancer has a poor prognosis, and more than half of patients recur in 2 y. External beam radiotherapy (EBRT) with concurrent chemotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer. The immunostimulatory activity of the PD-1 inhibitor pembrolizumab (pembro) may be enhanced by concurrent chemoradiotherapy (CRT). After the KEYNOTE-158 study, in which pembro showed durable antitumor activity, pembro monotherapy was approved for patients with PD-L1–positive recurrent or metastatic cervical cancer who progressed during or after chemotherapy. ENGOT-cx11/KEYNOTE-A18 (NCT04221945) is a phase III, randomized, placebo-controlled study evaluating pembro with concurrent CRT for the treatment of locally advanced cervical cancer. Methods: Approximately 980 patients with high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA), locally advanced, histologically confirmed cervical cancer who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive either 5 cycles of pembro 200 mg every 3 wk (Q3W) + CRT followed by 15 cycles of pembro 400 mg Q6W or 5 cycles of placebo Q3W + CRT followed by 15 cycles of placebo Q6W. The CRT regimen includes 5 cycles (with optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT followed by brachytherapy. Randomization is stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cancer stage at screening (stage IB2-IIB vs III-IVA), and planned total radiotherapy dose. Treatment will continue until the patient has received 20 cycles of pembro (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 y) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are PFS per RECIST v1.1 by blinded independent central review and OS. Secondary endpoints are PFS at 2 y, OS at 3 y, complete response at 12 wk, ORR, PFS and OS in PD-L1–positive patients, EORTC QLQ-C30 and QLQ-CX24, and safety. Enrollment is ongoing. Clinical trial information: NCT04221945.

Comparison of Nedaplatin- and Cisplatin-Based Concurrent Chemoradiotherapy in Locally Advanced Cervical Cancer Patients: A Propensity Score Analysis

2018 ◽  
Vol 28 (5) ◽  
pp. 1029-1037
Author(s):  
Ping Li ◽  
Rui Zhang ◽  
Zhihua Nie ◽  
Mengjuan Long ◽  
Gong Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Propensity Score ◽  
Concurrent Chemoradiotherapy ◽  
Propensity Score Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Advanced Cervical Cancer ◽  
Free Survival ◽  
Locally Advanced Cervical Cancer ◽  
Score Analysis

PurposeThe aim of this study was to evaluate the efficacy of using nedaplatin to replace cisplatin for concurrent chemoradiotherapy (CCRT) in patients with newly diagnosed locally advanced cervical cancer.MethodsThe medical records of 155 patients with cervical cancer who had undergone CCRT with cisplatin (n = 85) or nedaplatin (n = 70) between January 2012 and January 2017 were retrospectively reviewed. Propensity score analysis with 1:1 matching with the nearest neighbor matching method was performed to assess response rates, progression-free survival, overall survival, and toxicity between 2 groups.ResultsPropensity score matching identified 63 patients in each group. After matching, compared with patients treated with cisplatin-based concurrent chemoradiotherapy (CisRT), we found that patients treated with nedaplatin-based concurrent chemoradiotherapy (NedaRT) had a significant higher recurrence rate (25.4% vs 42.9%; P = 0.04). In addition, the 3-year progression-free survival rate for NedaRT group was also worse than that for the CisRT group (52.2% vs 63.4%, P = 0.03). There was no difference in the overall response rates between the CisRT and NedaRT groups (87.3% and 90.5%, respectively; P = 0.57). The rates of 3-year overall survival and grades 3 to 4 toxicities were similar between the 2 groups.ConclusionsThe clinical outcome of this cohort of patients with locally advanced cervical cancer treated with CCRT did in no way provide support for the use of nedaplatin in place of cisplatin in chemoradiation and demonstrated no equivalence of the 2 drugs. Cautions should be taken for the replacement among platinum complexes in cancer treatment.

Therapeutic efficacy of epidermal growth factor receptor monoclonal antibody combined with concurrent chemoradiotherapy in treatment of locally advanced cervical cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17012-e17012
Author(s):  
Wenli Chen ◽  
Tao Li ◽  
Wei Zhang ◽  
Jialin Yang ◽  
Jian Wang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Control Group ◽  
Study Group ◽  
Advanced Cervical Cancer ◽  
Free Survival ◽  
Locally Advanced Cervical Cancer

e17012 Background: There are few studies about epidermal growth factor receptor monoclonal antibody nimotuzumab for the treatment of locally advanced cervical cancer. We aimed to assess the therapeutic efficacy and analyse prognostic factors of chemoradiotherapy combined with nimotuzumab in cervical cancer (stage IIB-IVA) . Methods: We retrospectively analyzed 23 patients with locally advanced cervical cancer(stage IIB-IVA) ,who received concurrent chemoradiotherapy combined with nimotuzumab from 2012 to 2014 (the study group) ,and 30 patients with the similar baseline characteristics who received concurrent chemoradiotherapy alone (the control group). The overall response rates, 5-year overall survival rates, progression-free survival and acute adverse events of the two groups were compared .Multivariate prognostic analysis was performed by a Cox proportional hazards model. Results: The median follow-up time were 46 months (IQR 16-60) in the study group and 42 months (2-60) in the control group.The overall response rates were 87% and 73.3% (P = 0.384) . The 5-year overall survival rates were 63.6% and 36.1% (hazard ratio 2.208,95% CI 0.878-5.557,P = 0.092) .The median progression-free survival in the study group was not achieved (95%CI 9-55) versus 27 months (1-60) in the control group (hazard ratio 2.635, 95% CI 1.030-6.737, P= 0.043).Multivariate prognostic analysis indicated that stage and whether to be combined with nimotuzumab were the influential factors for progression-free survival time.Adverse events were similar between groups.The most common grade 3 or 4 adverse events during treatment in the study group versus the control group were leucopenia(9 [39%] vs 11 [36%]),thrombocytopenia (3 [13%] vs 6 [20%]),anaemia (4 [17%] vs 4 [13%]). Conclusions: Concurrent chemoradiotherapy combined with nimotuzumab in the treatment can improve the progression-free survival time of advanced cervical cancer, while not increasing the incidence of adverse reactions.However, because of the small size of sample in this research, these findings suggest that it is necessary to perform a prospective study with expanded sample size.

Phase III placebo controlled double blind randomized trial of radiation therapy for stage 2B-4A cervical cancer with immunomodulator Z-100: JGOG-DT101 study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5506-5506 ◽  
Author(s):  
Keiichi Fujiwara ◽  
Yasuo Ohashi ◽  
Kazunori Ochiai ◽  
Kiichiro Noda
Keyword(s):  
Cervical Cancer ◽  
Radiation Therapy ◽  
Randomized Trial ◽  
Locally Advanced ◽  
Survival Rates ◽  
Phase Iii ◽  
Advanced Cervical Cancer ◽  
Double Blind ◽  
Locally Advanced Cervical Cancer ◽  
Platinum Based Chemotherapy

5506 Background: We previously reported that the lower dose (0.2 μg) of immunomodulator Z-100 showed better overall survival (OS) compared to higher dose (40 μg) in patients with locally advanced cervical cancer who received radiation therapy (RT). Therefore, we conducted a placebo controlled double-blind randomized trial to elucidate the role of additive immunotherapy in standard RT. Methods: Patients of stages 2B to 4A squamous cell carcinoma of the uterine cervix, who were scheduled to receive standard RT with or without platinum-based chemotherapy, were eligible. Z-100 at 0.2 μg (Z) or placebo (P) was given subcutaneously twice a week during the RT, followed by maintenance therapy by administering either Z or P once every two weeks. Therapy was continued until disease progression or termination of the trial in2011. Primary endpoint was OS, secondary endpoints were recurrent-free survival (RFS), response rate (RR), and safety. Sample size was calculated by assuming 5-year survival rates (5YSR) as 60% in Arm Z and 38-44% for Arm P, (hazard ratio HR: 0.526-0.625), and was determined to be 120 patients in each arm. Results: Between 2004 and 2006, 249 patients were randomized. Total of 244 patients were eligible for safety analysis, and 243 patients were eligible for survival analysis. In Arm Z, 29 deaths were reported, and in Arm P, 42. 5YSR was 75.7% (95%CI: 66.4-82.8%) for Arm Z and 65.8 % (95%CI: 56.2-73.8%) for Arm P; HR was 0.646 (95%CI: 0.400-1.043). Survival benefit in Arm Z was observed regardless of chemoradiation or radiation alone. There were no differences between arms in terms of RR and RFS, and side effects. Neoplasms, including benign cases, observed were 4 in Arm Z, and 13 in Arm P. Conclusions: Immunomodulator Z-100, used as an adjuvant therapy after radiation, showed clinically significant improvement of OS in locally advanced cervical cancer, although the statistical power was less than anticipated because survival rates were unexpectedly higher than expected for both arms. Further exploration of Z-100 is warranted. Clinical trial information: C000000221.

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