Clinical Research Directory

Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (eVOLVE-Cervical)

This is a phase III, randomized, double-blind, placebo-controlled, multi-center, global study to explore the efficacy and safety of volrustomig in women with high-risk LACC (FIGO 2018 stage IIIA to IVA cervical cancer) who have not progressed following platinum-based CCRT.

Cadonilimab Combined With RT in LACC Patients Ineligible for CCRT

Concurrent chemoradiotherapy (CRT) is the standard of care for locally advanced cervical cancer (LACC). However, a substantial proportion of patients have contraindications to cisplatin based chemotherapy due to advanced age, renal impairment, cardiac dysfunction, or other comorbidities. For these patients, no evidence based standardised treatment exists. Immunotherapy combined with radiotherapy may offer a chemotherapy sparing alternative. Cadonilimab, a PD 1/CTLA 4 bispecific antibody, has demonstrated significant efficacy in advanced cervical cancer. This study aims to evaluate the efficacy and safety of cadonilimab combined with radical radiotherapy in LACC patients ineligible for concurrent chemotherapy. This is an investigator initiated, prospective, single centre, single arm, open label, Simon's two stage phase II trial. A total of 45 patients will be enrolled. Eligible participants are women aged \>18 years with histologically confirmed cervical squamous cell carcinoma or adenosquamous carcinoma, FIGO 2018 stage IB3-IVA, and absolute or relative contraindications to cisplatin based chemotherapy. All patients will receive radical radiotherapy (external beam radiotherapy 45-50.4 Gy/25-28 fractions plus high dose rate brachytherapy 6-8 Gy × 3-5 fractions) concurrently with three cycles of cadonilimab 10 mg/kg intravenously every 3 weeks. The primary endpoint is complete response (CR) rate assessed at 4 weeks post radiotherapy. Secondary endpoints include 2 year progression free survival, 2 year local control, 2 year locoregional control, 5 year overall survival, safety (CTCAE v5.0 and RTOG late toxicity), and quality of life (EORTC QLQ C30 and QLQ BR23). Assuming a historical CR rate of 69% with radiotherapy alone, we hypothesise that the combination will increase CR to 85%. With α=0.05 (two sided) and 80% power, Simon's optimal two stage design requires 43 evaluable patients; after accounting for 5% dropout, 45 patients will be recruited.

Clinical Feasibility of the ARCHITECT Applicator in Cervical Cancer Brachytherapy

This prospective, non-randomised, single centre, phase I trial assesses the clinical feasibility of the use of the patient-tailored ARCHITECT applicator in locally advanced cervical cancer brachytherapy.

A Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (IVOLGA)

This is a phase II single-arm open-label study to investigate the efficacy and safety of volrustomig in women with FIGO 2018 stage IIIA to IVA cervical cancer who have not progressed following platinum-based concurrent chemoradiation therapy (CCRT).

A Clinical Study of Nanocrystalline Megestrol Acetate in Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer

Cervical cancer, ranking as the fourth most prevalent malignancy in women globally, presents significant challenges in nutritional management. Approximately 31% of patients develop cancer-related malnutrition/cachexia, with 10-20% of deaths directly attributable to nutritional depletion. The disease process and its treatment - particularly concurrent chemoradiotherapy (CCRT) - create a destructive cycle through multiple mechanisms. Tumor-derived factors (including activins and myostatin) and inflammatory cytokines (such as TNF-α and IL-6) actively promote muscle and fat catabolism. CCRT toxicity, especially from platinum-based drugs, worsens this condition by inducing mitochondrial dysfunction and accelerating protein degradation, leading to clinically significant sarcopenia. This metabolic disruption has dire consequences, with studies showing severe weight loss during CCRT correlating with a 2.37-fold increase in mortality risk (HR 2.37, p=0.036). Nanocrystalline megestrol acetate (MA) emerges as a promising therapeutic intervention with dual mechanisms of action. Centrally, it modulates D2 receptors to upregulate neuropeptide Y (NPY), effectively stimulating appetite. Peripherally, it suppresses key inflammatory cytokines (IL-6 and TNF-α), thereby reducing systemic inflammation and muscle wasting. Its efficacy is well-established, with endorsement from major oncology guidelines (ASCO, NCCN, ESMO) for cancer cachexia management. A comprehensive meta-analysis of 35 clinical trials involving 4,234 patients demonstrated MA's superiority over placebo, showing significant improvements in appetite (RR 2.2), weight gain (RR 1.6), and quality of life (RR 1.8). The nanocrystalline formulation represents a substantial pharmacological advancement over conventional MA. While traditional preparations have limited solubility (2 µg/mL) and require high-fat meals for adequate absorption, the nanocrystalline version (with particles reduced to 26.6 nm) demonstrates 22% greater bioavailability. This translates to clinically meaningful differences: fasting-state peak concentrations increase from 187 ng/mL to 1,133 ng/mL, the time to observable effect shortens from 14 days to just 3 days, and 12-week weight gain improves from 3.5 kg to 5.4 kg (with 40% being lean mass). Dose optimization studies confirm 800 mg/day as the optimal conventional MA dose, with the nanocrystalline equivalent being 625 mg/day due to its enhanced bioavailability. The proposed clinical investigation will evaluate this intervention in FIGO IB3-IVA cervical cancer patients (n=5) undergoing CCRT. The study employs a two-arm design comparing nanocrystalline MA (625 mg/day) plus CCRT against CCRT alone. Primary endpoints focus on BMI changes at 8 weeks, with secondary assessments of nutritional status, inflammatory markers, and quality of life measures. This research aims to establish nanocrystalline MA as a means to break the cachexia cycle in cervical cancer treatment, potentially improving both treatment tolerance and survival outcomes.

This is a Multicentre International Study Evaluating CT-based IGABT With / Without Either TRUS During BT/Pre BT MR as Per IBS-GECESTRO-ABS Recommendations for Target contouring-as an Alternative to MRIGABT for Cervical Cancer From Implementation Perspectives Under EMBRACE-III:TRIPLET IMPACT Study.

Title: Integration of Multi-modality Imaging Protocols with Emphasis on CT in Image-Guided Adaptive Brachytherapy (IGABT) for Cervical Cancer - EMBRACE III-TRIPLET : IMPACT Study Locally advanced cervical cancer (LACC) remains a major health challenge, particularly in low- and middle-income countries (LMICs), which account for the majority of global cases. The standard curative treatment involves a combination of external beam radiotherapy (EBRT) with concurrent chemotherapy, followed by brachytherapy (BT). Brachytherapy plays a crucial role in achieving high local control by delivering radiation directly to the tumour through internally placed radioactive sources. Historically, BT dose prescription was based on two-dimensional (2D) X-ray images and defined anatomical "points," achieving 5-year local control rates of 60-70%. Over the last decade, magnetic resonance imaging (MRI)-based image-guided adaptive brachytherapy (MR-IGABT) has transformed practice by enabling three-dimensional (3D) target-based dose prescription and adaptation to tumour regression. The landmark EMBRACE I study, involving over 1300 patients, demonstrated over 90% 5-year local control rates with MR-IGABT, establishing it as the international gold standard endorsed by NCG, ICRU, NCCN, and ESGO-ESTRO guidelines. However, MRI-based planning for IGABT remains logistically and financially challenging for many centres, especially in LMICs. CT and transrectal ultrasound (TRUS) have emerged as feasible alternatives, offering broader accessibility. Despite encouraging outcomes from smaller institutional studies, the lack of standardized and validated target delineation concepts for CT-IGABT has led to significant variability in clinical implementation. Recognizing this, the Indian Brachytherapy Society (IBS), American Brachytherapy Society (ABS), and GEC-ESTRO jointly published consensus recommendations in 2020 to standardize CT-IGABT practices across diverse clinical environments. At Homi Bhabha Cancer Hospital and Research Centre, Visakhapatnam, our prior work (RetroLACER Study) demonstrated that CT-based IGABT can achieve outcomes comparable to MR-IGABT, highlighting its feasibility and potential for wider adoption. Building on this foundation, the EMBRACE III-IMPACT Study seeks to evaluate whether CT-IGABT can be systematically and uniformly implemented in a multi-centre setting and to benchmark clinical outcomes against the standards set by MR-IGABT. Study Design: This is a multicentre, prospective, observational study planned to include approximately 1200 participants with locally advanced cervical cancer. All participants will receive standard-of-care treatment, including EBRT, concurrent weekly cisplatin chemotherapy, and brachytherapy with image-guided planning. Objectives: To assess the feasibility of implementing standardized CT-IGABT protocols across diverse clinical environments. To evaluate local control, disease-free survival, and treatment-related toxicity outcomes for CT-IGABT. To compare and benchmark CT-IGABT outcomes with established MR-IGABT benchmarks from prior international studies. Participant Involvement: Participants will undergo standard diagnostic imaging, EBRT with weekly cisplatin, and brachytherapy using CT-based planning. Imaging and treatment data will be collected, anonymized, and submitted to a central database for review. Regular follow-up visits will monitor tumour control and treatment-related side effects. Benefits: Participants receive internationally standardized, quality-assured treatment protocols. Centres gain access to expert review and QA support from international collaborators, potentially improving treatment quality and outcomes. The study supports global efforts to establish CT-IGABT as a cost-effective, accessible alternative to MRI-based IGABT, expanding equitable cancer care access. Risks: The study is observational and involves standard treatment; therefore, risks and costs are comparable to routine cervical cancer care. Confidentiality and Ethics: All data will be anonymized and handled in compliance with ethical and regulatory standards. Participant confidentiality will be strictly maintained. Written informed consent will be obtained before study participation. Significance: By validating standardised CT-based protocols and establishing outcome benchmarks, the study aims to facilitate widespread adoption of IGABT in resource-limited settings, ultimately improving treatment accessibility and survival outcomes.

MicroEnvironment Tumor Effects of Radiotherapy - Comprehensive Radiobiology Assessment TRial

This study is a dynamically adjustable prospective longitudinal study designed to capture biospecimen (biopsy, blood, surgical) and multimodal treatment-related data (imaging, dosimetry, clinical) before, during, and after treatment with definitive-intent chemoradiotherapy for patients with locally advanced cervical and pancreatic cancer.

QL1706 Plus Neoadjuvant Chemotherapy Followed by Type I Hysterectomy for Locally Advanced Cervical Cancer

The goal of this clinical trial is to determine the effectiveness of the combination therapy of Eparbrutinib (QL1706) with neoadjuvant chemotherapy followed by Type I hysterectomy in treating locally advanced cervical cancer. Additionally, it will assess the safety profile of this treatment regimen. The main questions it aims to answer are: 1. Does the combination of Eparbrutinib (QL1706) with neoadjuvant chemotherapy lead to a higher rate of complete pathological response (pCR) compared to chemotherapy alone? 2. What are the medical complications and side effects experienced by participants during the treatment with Eparbrutinib (QL1706)? Researchers will compare the outcomes of patients receiving Eparbrutinib (QL1706) combined with neoadjuvant chemotherapy to those receiving standard treatment to evaluate the effectiveness in treating locally advanced cervical cancer. Participants will: 1. Take Eparbrutinib (QL1706) alongside cisplatin and albumin-bound paclitaxel every three weeks for three cycles. 2. If the lesion was reduced to less than or equal to 2cm, conectomy was performed; if the pathological results indicated no high-risk factors, total hysterectomy was performed, and QL1706+TC was treated after surgery. If the lesion is larger than 2cm, a type III hysterectomy is performed and adjuvant treatment is determined according to sedlis criteria after surgery. 3. Visit the clinic regularly for checkups, tests, and assessments throughout the treatment period. 4. Keep a diary of their symptoms, side effects, and any changes in their health status. This study is designed to provide insights into the potential benefits of adding Eparbrutinib (QL1706) to the standard neoadjuvant chemotherapy regimen for locally advanced cervical cancer, which may lead to improved treatment outcomes and survival rates for patients.

Neoadjuvant Iparomlimab and Tuvonralimab Plus Chemotherapy-eclipse for Locally Advanced Cervical Cancer (NICE-CC)

Locally advanced cervical cancer (LACC) remains a significant global health concern with limited treatment options. Recent advancements suggest that using neoadjuvant anti-PD-1 inhibitors in combination with chemotherapy, followed by radical surgery, may be an effective treatment strategy for patients with PD-L1-positive LACC. This study aims to evaluate the efficacy and safety of preoperative treatment with iparomlimab and tuvonralimab-a bifunctional PD-1/CTLA-4 dual blocker-combined with chemotherapy for LACC.

Neoadjuvant Chemotherapy Plus Cadonilimab for Locally Advanced Cervical Cancer

Main Purpose of this study is to determine the efficacy and safety of Cadonilimab combined with chemotherapy (cisplatin) for locally advanced cervical cancer. This is an multicentre, single Arm, Phase 2 Trial study of Cadonilimab with Cisplatin in the treatment of locally advanced cervical cancer. 29 eligible patients will receive Cadonilimab（10mg/kg, iv., D1, q3w）with Cisplatin ( 75mg/ m2, iv., D2， q3w) for a total of 2-4 cycles before radical surgical treatment.

Study on Disease Characteristics and Treatment in Locally Advanced or Recurrent / Metastatic Cervical Cancer in Italy

Multicenter, Observational, Retrospective charts review. Observational study with descriptive purpose only. Retrospective data capture in consecutive patients diagnosed with CC who attended the Oncologic Clinics from Jan 2018 to Dec 2021 (using medical records, either electronic or not), inserted in eCRF and analyzed.

Evaluation of Concomitant Chemo-radiotherapy With Cisplatine vs Gemcitabin in Locally Advanced Cervicouterine Cancer

The purpose of this phase III clinical trial, is to evaluate the efficacy and safety of concomitant chemo-radiotherapy with Cisplatin vs Gemcitabine as the first line of treatment in patients with locally advanced cervical cancer, with comorbidities and preserved renal function.

Curcumin Supplementation in Cervical Cancer

Brief Summary. The goal of this pilot study is to learn about the effect of curcumin supplementation in locally advanced cervical cancer patients. The main questions it aims to answer are: * Does curcumin supplementation increase the levels of p53 and apoptosis in tumor cells from cervical cancer patients? * At which dose of curcumin supplementation is the broader effect observed for p53 expression and apoptosis in tumor cells from cervical cancer patients? * Are all doses safe for supplementation? Participants will be asked to take curcumin tablets throughout their cancer treatment. Researchers will compare 6 different groups, each group will receive a different dose of curcumin with or without piperin, to see the dose with the broader effect and safety of curcumin supplementation: 1. 1 g of curcumin 2. 1 g of curcumin + piperine 3. 3 g of curcumin 4. 3 g of curcumin + piperine 5. 6 g of curcumin 6. 6 g of curcumin + piperine

Neoadjuvant Chemo-immunotherapy Followed by Concurrent Chemoradiotherapy and Immunotherapy in LACC

Concurrent chemoradiotherapy -immunotherapy followed by ICI maintenance was proved to improve the PFS by the Keynote-A18 in the LACC patients, and still more than 30% progressed. Neoadjuvant chemo-immunotherapy in LACC resulted in higher pCR rate. This prospective single arm study is to investigate the efficacy and safety of neoadjuvant immuno-chemotherapy followed by concurrent chemoradiotherapy and consolidative immunotherapy in LACC patients.

Neoadjuvant Immunochemotherapy in PD-L1-negative LACC

This is a multicenter, prospective, single-arm, phase 2 clinical trial designed to evaluate the therapeutic efficacy of the NACI (neoadjuvant chemotherapy plus Camrelizumab) for PD-L1-negative locally advanced cervical cancer.

A Clinical Study of Pelvic Concurrent Chemoradiotherapy Combined with CT-guided Intracavitary Brachytherapy with Adaptive Simultaneous Dose Escalation for Locally Advanced Cervical Cancer

The standard treatment for locally advanced cervical cancer is cisplatin-based concurrent chemoradiotherapy with external beam radiotherapy (EBRT) and Brachytherapy (BT). overall treatment time (OTT) has been found to be an important predictor of treatment response. Some studies have shown that the acceleration of tumor cell regeneration during the extension of radiotherapy leads to poor local control. Prolonging the overall treatment time of cervical cancer radiotherapy for more than 8 weeks leads to an increase in pelvic local control failure. Therefore, shortening OTT has great potential benefits from both clinical efficacy and social benefits. Shortening OTT in radical cervical cancer radiotherapy includes hypofractionated EBRT and shortening the interval between BT and EBRT. However, further shortening OTT may lead to an increase in acute and late toxicity. Adaptive radiotherapy (ART) strategies systematically monitor variations in target and neighbouring structures to inform treatment-plan modification during radiotherapy. The application of image-guided adaptive brachytherapy (IGABT) has clearly demonstrated the advantages of this approach in the treatment of cervical cancer. Previous studies have shown that the implementation of IGABT can achieve personalized treatment, dose increase, improve clinical efficacy, reduce normal tissue toxicity and side effects, and strengthen international standardized quality control. In this study, online adaptive pelvic EBRT combined with IGABT based on uRT-linac was performed under online CT guidance. The aim of this study is to evaluate the safety and efficacy of pelvic concurrent chemoradiotherapy combined with CT-guided intracavitary brachytherapy with adaptive simultaneous dose escalation in locally advanced cervical cancer.

Study of Laparoscopic Radical Hysterectomy Based on Space Anatomy in Patients With IB3 and IIA2 Cervical Cancer

Radical hysterectomy is an effect treatment for FIGO IB3 and IIA2 cervical cancer patients who refuse to receive radical concurrent chemoradiotherapy. However, due to the large tumor size, both patients and surgeons encountered the risk of substantial bleeding, urinary tract damage, and unsatisfactory resection during surgery. Therefore, the exploration of effective and safe surgical treatments is crucial in enhancing the quality of life and prognosis for patients. Laparoscopic radical hysterectomy (LRH) offers the advantages of reduced bleeding and accelerated recovery, thereby minimizing patient discomfort and enhancing their quality of life. However, the prognosis of patients who received LRH or traditional abdominal radical hysterectomy (ARH) remains controversial. We proposed a modified LRH skill based on new space anatomy concept. In our previous single-center study, the result demonstrates that LRH based on space anatomy leads to less intraoperative blood loss and decreased ureteral injury rate compared with traditional skill. The benefits of this new method for patient survival remain uncertain. In this multicenter retrospective study, we aim to assess clinical prognosis and safety of this new LRH compared with traditional abdominal radical hysterectomy (ARH) in FIGO IB3 and IIA2 cervical cancer.

A Study of Chemoradiotherapy With SHR-1316 For Treatment of Locally Advanced Cervical Cancer

The Primary purpose of this study is to evaluate the safety of SHR-1316 plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer. The second purpose of this study is to evaluate the efficacy and PK traits; The exploratory study is to explore the biomarker 、immunogenicity and so on .

CNCMT：a Multi-center, Prospective, Single-arm Study

To evaluate the safety and efficacy of Cadonilimab in neoadjuvant chemotherapy and maintenance therapy for high-risk advanced cervical cancer receiving concurrent chemoradiotherapy

Neoadjuvant Chemoimmunotherapy Versus Concurrent Chemoradiotherapy for LACC

It is a prospective, open-label, randomized, controlled phase II/III clinical trial in which patients with PD-L1-positive FIGO stage IB3, IIA2 and IIB（tumors \>4 cm in diameter）will be enrolled and randomly divided into the neoadjuvant chemoimmunotherapy plus surgery group and the CCRT group.

Study Of Cadonilimab Combined With Radiotherapy In The Treatment of Locally Advanced Cervical Cancer

Cadonilimab（AK104）is a humanized IgG1 bispecific antibody that targets PD-1 and CTLA-4. This is a single-arm, multicenter, open-label, phase II study, the purpose of this study is to evaluate the efficacy and safety of Cadonilimab plus radiotherapy in participants with locally advanced cervical cancer who do not tolerate chemotherapy.

Zimberelimab Combined With Albumin-bound Paclitaxel and Cisplatin in Neoadjuvant Treatment of LACC

This is a prospective, single arm, phase II clinical study to evaluate the efficacy and safety of Zimberelimab combined with albumin-bound paclitaxel and cisplatin as neoadjuvant therapy for locally advanced cervical cancer.

Comparing the Efficacy of Surgery Staging and Image Staging of Locally Advanced Cervical Cancer

The study is a domestic multicenter, prospective, non-randomized controlled concurrent trial. It will be assessed whether surgery staging on locally advanced cervical cancer is superior to image staging for improving progression-free survival and overall survival.

Study on the Relationship Between Plasma MRD and cfDNA HPV and the Efficacy and Prognosis of Locally Advanced Cervical Cancer After Concurrent Chemoradiotherapy

Cervical cancer CC is the most common malignant tumor in the female reproductive system, seriously endangering women's health and life, and is one of the leading causes of death for women worldwide.Globally, HPV causes about 85% of cervical cancers and about 60% of oropharyngeal cancers, causing more than 500,000 cancers each year.ctDNA is a potential biomarker because it contains tumor-specific genetic and epigenetic abnormalities that can be used in cancer diagnosis and prognosis prediction.MRD is considered a promising prognostic marker that can be used to identify individuals at increased risk of recurrence and individuals who may benefit from treatment.The expression level of MRD and plasma HPV before and after radiotherapy and chemotherapy for cervical cancer was analyzed by liquid biopsy ctDNA detection technology, which predicted the efficacy of cervical cancer radiotherapy and chemotherapy, which was helpful for monitoring and estimating the risk of disease recurrence after cervical cancer radiotherapy and chemotherapy, and verified the expression of MRD and plasma HPV as the basis for adjuvant chemotherapy after cervical cancer radiotherapy and the basis for optimal chemotherapy time node selection.