Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Tubulin Modulators

Antimitotic Agents

docetaxel

Radiation Therapy

Yuhchyau Chen, MD, Ph.D

The purpose of this study is to find out how effectively cervix cancer is controlled when radiation is combined with low-dose chemotherapy (Taxotere) . The use of low-dose Taxotere, once per week, with radiation is a new treatment for cervical cancer. This study will also see how well this treatment regimen can be tolerated.

Low-Dose Taxotere® (Docetaxel) With Concurrent Radiotherapy For Localized, Inoperable Carcinoma Of The Uterine Cervix

A Phase Ii Clinical Study Using Weekly Low-Dose Taxotere® (Docetaxel) With Concurrent Radiotherapy For Localized, Inoperable Carcinoma Of The Uterine Cervix

University of Rochester

Yuhchyau Chen, MD,Ph.D

Symptoms and General Pathology

Recurrence

Antibodies

Immunoglobulins

Histone Deacetylase Inhibitors

In combination dose finding phase, phase 1b will begin with Dose Level 1: chidamide 30 mg/day orally (twice a week) and toripalimab (240mg q3w, intravenously) will be administered to eligible subjects on a 21-day treatment cycle. Two dose de-escalation steps are included: Dose Level 2 (chidamide 25 mg/day orally, twice a week and toripalimab 240mg q3w, intravenously) and Dose Level 3 (chidamide 20 mg/day orally, twice a week and toripalimab 240mg q3w, intravenously). If RP2D was reached in Part A, eligible patients would be enrolled and receive toripalimab (240mg q3w, intravenously) plus chidamide (RP2D, twice a week).

Toripalimab + Chidamide

Chunyan Lan

Xin Huang

Cervical cancer is the second-most common cancer in the world and is a leading cause of cancer death among women in developing countries. Cisplatin-based chemotherapy +/- bevacizumab have been recommended as the first-line treatment for patients who present with metastatic (e.g. stage IVB), persistent, or recurrent cervical cancer. However, patients in this setting are rarely curable. Pembrolizumab has been approved for second-line treatment in patients with advanced PD-L1-positive cervical cancer. However, the response rate achieved by PD-1 inhibitors as monotherapy is only modest. Preclinical studies found that in mouse models of B-cell lymphoma, adding a histone deacetylase (HDAC) inhibitor sensitized cancers to anti-PD-1 therapy. Recently, combination treatment of HDAC inhibitors with immune checkpoint inhibitors is widely investigated and has promising results in several cancer types. Toripalimab is a humanized IgG4 monoclonal antibody against PD-1. Chidamide is a class I HDAC inhibitor. Here we conducted a phase Ib/II, single-arm, multi-center study to evaluate the efficacy and safety of toripalimab in combination with chidamide in patients with metastatic, persistent, or recurrent cervical cancer.

There are two main parts to this study; Part A, combination dose finding and Parts B, dose expansion. Part B will either be initiated if RP2D reached in Part A, or not initiated if RP2D was not reached in Part A. Part A has been designed to identify the recommended dose of combination of toripalimab plus chidamide for further clinical evaluation based upon assessment of the safety and tolerability data collected during the first 28 days. "3+3"design was used in the dose finding cohort. If RP2D was reached in Part A, eligible patients would be enrolled and receive toripalimab (240mg q3w, intravenously) plus chidamide (RP2D, twice a week) till disease progression (PD) withdraw of consent, or unacceptable toxicity.

Anti-PD-1 Antibody Combined With Histone Deacetylase Inhibitor in Patients With Advanced Cervical Cancer

Toripalimab, a Anti-PD-1 Antibody, and Histone Deacetylase Inhibitor Chidamide in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer, a Multicenter, Open-label, Single-arm, Phase Ib/II Trial

Dose-limiting toxicities (DLTs) are defined as: grade 3 febrile neutropenia, grade 4 hematologic toxicities, and grade 3 non-hematologic toxicities according to CTCAE v5.0

ORR is the proportion of patients with best response of complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Time from the date of first study treatment administration to the date of first documented tumor progression or death due to any cause, whichever occurs first.

Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first.

Proportion of patients whose best overall response is either CR, PR, or SD according to RECIST v1.1.

Time from the date of first study treatment administration to the date of death due to any cause.

Incidence of Adverse Event reported per CTCAE v5.0

Sun Yat-sen University

Professor

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Tomotherapy Treatment Planning

Don Yee, MD

Standard treatment for non-operable cervix cancer is radiation and chemotherapy. This treatment combination can result in significant radiation side-effects involving the bladder, small bowel and rectum. To improve results with radiation/chemotherapy, higher radiation doses have been tried for cervix cancer patients. Results from using higher radiation doses show that cervix tumours may be better controlled, but the radiation side-effects are worsened. Intensity modulated radiotherapy (IMRT) and Tomotherapy are new radiation planning and delivery technologies which may allow for delivery of higher radiation doses with less damage to normal organs. The purpose of this project is to determine whether or not IMRT and/or Tomotherapy technology can produce radiation plans that deliver higher doses of radiation to the tumor and lower doses to normal organs when compared to standard radiation plans. The results from this project will provide the basis for possibly treating future cervix cancer patients with Tomotherapy and providing them with improved cure rates along with decreased rates of radiation side effects. No patients will be treated on this protocol, as the investigators plan to only compare radiation dose calculations from different treatment plans created for test cervix cancer cases. There will be absolutely no patient contact in this protocol.

Background Information:

The addition of concurrent chemotherapy to radiotherapy (RT) for locally-advanced cervix cancer has improved patient outcomes, but treatments are associated with significant rates of radiotherapy (RT)-related toxicities. Plus, the disease-free and overall survival benefits conferred by concurrent chemotherapy appear to be most prominent in patients with earlier stage disease. Limits to RT for cervix cancer which can impact patient outcomes are overall treatment time and RT dose. Attempts to overcome these limits have been made in trials using altered RT fractionation schemes. Promising rates of local control reported in these trials are offset by excessive rates of acute and late RT-related toxicities.

Intensity-modulated radiotherapy (IMRT) is innovative RT planning and delivery technology with the ability to vary the intensity of radiation across a beam, allowing for increased conformity of RT dose around target volumes along with decreased dose delivered to normal structures. Tomotherapy uses an intensity-modulated beam which rotates around the patient as the patient is being translated longitudinally through the gantry and features the ability to acquire megavoltage CT (MVCT) images of target structures at each treatment. It is thought that Tomotherapy can plan and deliver more conformal RT with the added advantage of daily assessment of target and critical structure position via MVCT imaging.

Experience with using IMRT for cervix cancer is sparse. Reports of treating pelvic nodal targets in small numbers of selected cervix cancer patients with IMRT suggests that the treatments are tolerable and associated with decreased incidences of acute and late RT-related toxicities compared with a similar patient cohort treated with conventional RT technologies. Currently, there is no published report of using Tomotherapy to plan or deliver RT using conventional or altered fractionation for cervix cancer patients.

The limitations of overall treatment time and the maximal dose of RT that can be safely delivered to the pelvis targets make cervical carcinoma a tumor in which Tomotherapy can potentially improve the therapeutic ratio. Tomotherapy's ability to deliver more conformal RT to target structures and minimize dose to normal structures may allow for delivery of altered fractionation radiation plans for cervix cancer with acceptable rates of RT-related toxicities. Tomotherapy allows for delivery of differential daily doses of RT to target volumes that lie within larger target volumes which in effect delivers a simultaneous integrated boost (SIB) to areas of gross disease which lie within a larger volume at risk for harbouring micrometastases. Delivery of the boost dose of radiation in a simultaneous as opposed to sequential fashion decreases the overall RT treatment time which theoretically reduces the effects of accelerated tumor cell repopulation. Delivering higher doses per fraction to areas of gross disease would theoretically increase the radiobiologic enhancement effects of concurrent cisplatin chemotherapy.

Tomotherapy represents a key advance in radiotherapy planning and delivery technology. Its potential dosimetric and radiobiologic advantages over standard radiotherapy technologies need evaluation in properly-conducted clinical trials. Prior to the initiation of such trials, it must be shown that Tomotherapy plans at least have dosimetric advantages over conventional plans.

Objective:

To compare radiotherapy (RT) plans created for locally-advanced cervix cancer cases using Tomotherapy, conventional computed tomography-based methods and step-and-shoot intensity-modulated methods.

Study Design:

Pre-treatment planning computed tomography scans of ten previously-treated cervix cancer patients will be used. All identifying patient data on these CT image sets will be completely removed. Three RT plans will be created for case: Tomotherapy, step-and-shoot IMRT, and conventional. The University Medical Centre in Utrecht, The Netherlands has implemented IMRT into clinical management of cervical cancer and the Gynecologic Oncology group there has graciously agreed to collaborate on this project by creating optimized step-and-shoot IMRT plans on our ten test cases. The anonymous CT image sets will be stored on data discs which will be sent via bonded courier to the University Medical Centre in Utrecht, The Netherlands for generation of step and shoot IMRT plans. Data to be calculated and collected from all plans include: dose-volume histograms (DVH's) for all target volumes and critical structures. Tumor Control Probability for targets and Normal Tissue Complication Probability for critical structures will be calculated. RT plans created on this protocol will only be used for dose and biophysical model calculation comparisons; no plan will be used to deliver actual radiation treatments to any patient. There will be absolutely no patient contact or interaction on this protocol.

Future Directions:

The investigators anticipate that results from this study will confirm the hypothesis that Tomotherapy plans incorporating a simultaneous integrated boost for cervix cancer will provide superior target volume coverage and normal critical structure avoidance when compared with step-and-shoot IMRT and conventional plans. Such confirmation will provide the basis to proceed with efforts to improve target and normal structure delineation for Tomotherapy treatment planning of cervix cancer using MRI-based planning. Ultimately, we plan to initiate phase I/II trials using MRI-based Tomotherapy planning and delivery techniques for cervix cancer patients. Incorporation of RT dose escalation and monitoring of treatment response with biologic imaging techniques for cervix cancer patients treated with Tomotherapy are other future potential areas of investigation.

Comparison of Tomotherapy Versus Intensity-modulated Step-and-shoot and Conventional Radiation Treatment Plans for Patients With Locally-advanced Squamous Cell Carcinoma of the Cervix

Alberta Health services

Gemcitabine

Cisplatin

Antimetabolites

Patients will be followed with computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

Receive two cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1 and gemcitabine 1000mg/m2 D1 and D8 at every 21 days. After that, patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

Two additional cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1 and gemcitabine 1000mg/m2 D1 and D8 at every 21 days.

cisplatin, gemcitabine

Follow-up

Michelle S Almeida, PhD

Rachel H Machado, MCS

This study hypothesizes that patients who persist with cell-free human papillomavirus deoxyribonucleic acid (cfHPV-DNA) plasma expression at the end of standard treatment, can derive the benefit of using adjuvant chemotherapy in locally advanced cervical cancer (CC). After standard treatment based on concomitant chemoradiotherapy regime, a qualitative and quantitative research of cfHPV-DNA in plasma of patients will be conducted. Those with a negative qualitative research result will leave the study. Patients who have positive research for plasma 16/18 cfHPV-DNA at the end of chemoradiotherapy treatment will be randomized to receive two additional cycles of adjuvant chemotherapy or observation. Patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

A prospective, randomized, multicenter, national, superiority, parallel, clinical trial, design to evaluate implementation components for conducting a national clinical trial using adjuvant chemotherapy in patients with locally advanced cervical cancer, selected by cfDNA-HPV biomarker. At the end of this pilot study, reaching feasibility goal, it is proposed to amplify size sample, with the same design.

Patients will be randomized by stratified randomization process to belong to one of the groups: control (Group B) or intervention (Group C), emphasizing homogeneity of risk factors between them. A randomized list will be generated by using a suitable software, using variable size blocks (2 or 4), with stratification for site and staging. The confidentiality of the randomization list will be maintained through an automated, centralized, Internet-based randomization system, available 24 hours a day (RedCap). Selected patients must receive standard treatment based on concomitant chemoradiotherapy regime, with dose of radiation of 40-50 greys (Gy) (considering additional boost of 10-15 Gy in lymph nodes, radiologically or surgically, compromised) and brachytherapy of 30-40 Gy and cisplatin 40mg/m2 weekly. After four weeks of the end of treatment, a qualitative and quantitative research of cfHPV-DNA in plasma of patients will be conducted. Those with a negative qualitative research result will leave the study. Patients who have positive research for plasma 16/18 cfHPV-DNA at the end of chemoradiotherapy treatment will be randomized to receive two additional cycles of adjuvant chemotherapy or observation. Patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

A prospective, randomized, multicenter, national, superiority, parallel, clinical trial, design to evaluate implementation components for conducting a national clinical trial using adjuvant chemotherapy in patients with locally advanced cervical cancer, selected by cfDNA-HPV biomarker. At the end of this pilot study, reaching feasibility goal, it is proposed to amplify size sample, with the same design. The participants will conduct a blood collection for research of cfDNA-HPV and will receive conventional treatment, gold standard currently, characterizing the descriptive phase of the research. In the second operational phase, it will happen the study randomization, designing an experimental study. The pilot study is scheduled to last one year and estimate the possibility to recruit between 30 and 50 patients during 2023.

Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer

Adjuvant Chemotherapy in Cell-free Human Papillomavirus Deoxyribonucleic Acid (cfHPV-DNA) Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer (CC)

Data could be shared after reasonable request of the principal investigator.

Accessing regulatory process, hiring and training of investigator sites.

Analyzing the impact of pandemic on disease diagnosis period.

Potential for recruiting 4 to 12 patients/month in each investigator site is sufficient to reach sample goal.

Validation of operation structure includes repository, data collection tools, logistics for intervention distribution (chemotherapy) to the participating sites, strategies for recruitment and stimulation of adherence to intervention and follow-ups.

Objectify 85% or more of adherence rates during intervention.

Aiming at reaching up to 20% during follow-ups and identification of critical factors for loss of follow-up and suggesting mitigation strategies.

Description of overall rates (non-comparative between treatment groups) of progression-free survival.

Description of overall rates (non-comparative between treatment groups) of overall survival.

Description of response rate via Response Evaluation Criteria In Solid Tumours (RECIST) criteria 1.1 2009.

Description of quality of life via European Organisation for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (QLC-C30) and a complementary module of the cervical cancer-specific Quality of Life module of the European Organization for Research and Treatment of Cancer (EORTC QLQ-CX24).

Description of tolerance to proposed intervention, by creating a Data and Safety Monitoring Board (DSMB).

University of Sao Paulo

Hospital do Coracao

Rare Diseases

Uterine Cervical Dysplasia

Precancerous Conditions

Cervical Intraepithelial Neoplasia

Pharmaceutical Solutions

Coagulants

Hemostatics

Experimental Arm. Haemostasis at the end of the procedure using vaginal packing and Monsel's solution.

Haemostasis at the end of the procedure using only Monsel's solution.

This study will evaluate the role of vaginal packing after cervical conization as haemostasis technique

Vaginal Packing

Ricardo D Reis, MD

The LEEP conization is commonly used for cervical pathologies treatment. The techniques for hemostasis usually used are: cautery, Monsel's solution and vaginal pack. Actually, there is no consensus about the best technique and there is not much information that validates the use of some of that. To compare the use or not of vaginal pack as methods of hemostasis after LEEP conization for management of cervical lesions.

A randomized clinical trial was conducted at Gynecology Oncology Department/Barretos Cancer Hospital for patients with indication of LEEP conization. After local IRB approval, patients were allocated in two arms (50 patients each): without vaginal pack (group 1 - GP1) and with vaginal pack (group 2 - GP2). The Monsel's solution was used in all patients. Intraoperative and postoperative outcomes will be evaluated: operative time, intraoperative and postoperative bleeding, hormonal status, age, parity and cone specimens' characteristics as well as short-term outcome were recorded and compared using Chi-square test, Fisher exact test and t-test where appropriate.

Patients were allocated in two arms (50 patients each): without vaginal pack (group 1 - GP1) and with vaginal pack (group 2 - GP2).Randomization was generated through a computer program creating a random entry list in the study, separating in group 1 (local application of Monsel's solution without intra-vaginal gauze buffer) and group 2 (application of Monsel's solution with intra-vaginal gauze). In this way, all patients had an equal chance of being included in both groups.

The allocation of patients to one group or another was only known moments before the surgical procedure was started.

Comparing Two Techniques of Haemostasis After Cervical Conization

Randomized Clinical Trial Comparing Two Techniques of Haemostasis After Cervical Conization With High Frequency Surgery

Bleeding was assessed by the need for reintervention.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Low-Dose Taxotere® (Docetaxel) With Concurrent Radiotherapy For Localized, Inoperable Carcinoma Of The Uterine Cervix	NCT00178269	Cervix Neoplasm	docetaxel Radiation Thera...	18 Years -	University of Rochester
Anti-PD-1 Antibody Combined With Histone Deacetylase Inhibitor in Patients With Advanced Cervical Cancer	NCT04651127	Cervical Cancer Cervix Cancer Cervix Neoplasm	Toripalimab + C...	18 Years - 70 Years	Sun Yat-sen University
Comparison of Tomotherapy Versus Intensity-modulated Step-and-shoot and Conventional Radiation Treatment Plans for Patients With Locally-advanced Squamous Cell Carcinoma of the Cervix	NCT00124488	Cervix Neoplasm	Tomotherapy Tre...	18 Years -	AHS Cancer Control Alberta
Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer	NCT05764044	Cervical Cancer Cervix Cancer Cervix Neoplasm	cisplatin, gemc... Follow-up	18 Years - 70 Years	Hospital do Coracao
Comparing Two Techniques of Haemostasis After Cervical Conization	NCT03293628	Cervical Intrae... Cervix Neoplasm	Vaginal Packing	19 Years - 68 Years	Barretos Cancer Hospital
Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer	NCT05764044	Cervical Cancer Cervix Cancer Cervix Neoplasm	cisplatin, gemc... Follow-up	18 Years - 70 Years	Hospital do Coracao
Low-Dose Taxotere® (Docetaxel) With Concurrent Radiotherapy For Localized, Inoperable Carcinoma Of The Uterine Cervix	NCT00178269	Cervix Neoplasm	docetaxel Radiation Thera...	18 Years -	University of Rochester

Spots Global Cancer Trial Database for cervix neoplasm