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.

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.

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.

scholarly journals HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer

ESMO Open ◽  
2021 ◽  
Vol 6 (3) ◽  
pp. 100154
Author(s):  
L. Cabel ◽  
C. Bonneau ◽  
A. Bernard-Tessier ◽  
D. Héquet ◽  
C. Tran-Perennou ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Locally Advanced ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Hpv Types ◽  
High Risk Hpv

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

A phase III trial of adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared to chemoradiation alone: The OUTBACK TRIAL.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS5116-TPS5116
Author(s):  
Linda R. Mileshkin ◽  
Kailash Narayan ◽  
Kathleen N. Moore ◽  
Danny Rischin ◽  
Edward Lloyd Trimble ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
New Zealand ◽  
Adjuvant Chemotherapy ◽  
Gynecologic Cancer ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase Iii ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
The Usa

TPS5116 Background: Cervical cancer is a global health problem and the most common cause of cancer-related death among women in developing nations. Despite the recently developed cervical cancer vaccine, many women will continue to die from cervical cancer for many decades unless existing treatments can be improved. Unscreened women often present with locally-advanced disease that has a 5 year overall survival (OS) rate of 60% or less following standard chemo-radiation. Although some evidence suggests that adjuvant chemotherapy following chemo-radiation may be of value, its role remains controversial. Methods: OUTBACK is a randomized phase III Gynecologic Cancer InterGroup (GCIG) trial designed and led by the Australia New Zealand Gynaecological Oncology Group (ANZGOG) in collaboration with the NHMRC Clinical Trials Centre. Participating countries (groups) include Australia and New Zealand (ANZGOG), India, the USA and Canada (GOG, RTOG). OUTBACK is suitable for women with locally advanced cervical cancer (FIGO stage IB1 and node positive, IB2, II, IIIB or IVA). The primary objective is to determine if the addition of adjuvant chemotherapy to standard cisplatin-based chemo-radiation improves OS. Women are randomized to either A) standard cisplatin-based chemo-radiation or B) standard cisplatin-based chemo-radiation followed by 4 cycles of carboplatin and paclitaxel chemotherapy. Secondary objectives are to compare progression-free survival, treatment-related toxicity, patterns of disease recurrence, quality of life and psycho-sexual health, and the association between radiation protocol compliance and outcomes. Blood and tumour samples are collected from consenting patients for future translational studies. 780 women will be enrolled to determine if the addition of adjuvant chemotherapy can improve the 5-year OS rate by ≥ 10%. OUTBACK opened in Australia and New Zealand in 2011. In early 2012 the trial opened in the USA and activation of GOG sites is ongoing. 15 patients have been randomized. It is expected that RTOG and India will open the trial later this year with recruitment increasing substantially once all sites are activated.

Long-Term Follow-Up of a Randomized Trial Comparing Concurrent Single Agent Cisplatin, Cisplatin-Based Combination Chemotherapy, or Hydroxyurea During Pelvic Irradiation for Locally Advanced Cervical Cancer: A Gynecologic Oncology Group Study

2007 ◽  
Vol 25 (19) ◽  
pp. 2804-2810 ◽  
Author(s):  
Peter G. Rose ◽  
Shamshad Ali ◽  
Edwin Watkins ◽  
J. Tate Thigpen ◽  
Gunter Deppe ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Relative Risk ◽  
Combination Chemotherapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Advanced Cervical Cancer ◽  
Pelvic Irradiation ◽  
Locally Advanced Cervical Cancer

Purpose We report the long-term survival and toxicity of a randomized phase III study comparing cisplatin alone with cisplatin, flurouracil, and hydroxyurea versus hydroxyurea concurrent with pelvic irradiation for patients with locally advanced cervical cancer with pathologically negative para-aortic nodes. Patients and Methods Comparisons of progression-free (PFS) and overall survival (OS) between treatment arms utilized Kaplan-Meier and log-rank statistics. Relative risk estimates adjusting for prognostic factors were determined using the Cox proportional hazards regression model. Pearson's χ2 test was used to assess differences in adverse events. Results The analysis included 526 patients. The median follow-up among surviving patients was 106 months. Consistent with the original report, improvement in PFS and OS was evident for both cisplatin-containing arms compared with hydroxyurea (P < .001). Analogous results were seen for stage IIB and for stage III disease (each P < .025). The relative risk of progression of disease or death was 0.57 (95% CI, 0.43 to 0.75) with cisplatin and 0.51 (95% CI, 0.38 to 0.67) with cisplatin-based combination chemotherapy compared with hydroxyurea. Among 518 patients who received radiation, acute (grade 3 or 4) gastrointestinal or urologic toxicities occurred in 66 with cisplatin (19.1%) and 29 with hydroxyurea (16.8%). Delayed radiation toxicity occurred in six patients who received cisplatin (1.7%) and two who received hydroxyurea (1.2%; P = .680). Conclusion Cisplatin-based chemotherapy during pelvic radiation therapy improves long-term PFS and OS among locally advanced cervical cancer patients collectively and for stage IIB and III disease, individually. There was no observed increase in late toxicity with cisplatin-based chemoradiotherapy.

Sign in / Sign up

Export Citation Format

Share Document