Symptoms and General Pathology

All Conditions

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Vomiting

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Signs and Symptoms, Digestive

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

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Doxorubicin

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Alkylating Agents

Neurokinin-1 Receptor Antagonists

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Neurotransmitter Agents

Arm 1, Single Dose: Fosaprepitant 150 mg intravenous (IV) Day 1 of Cycle 1 or Day 1 of Cycle 2. Participants randomized to Group 1 (Fosaprepitant Cycle 1 + No Fosaprepitant Cycle 2); or Group 2 (No Fosaprepitant Cycle 1 and Fosaprepitant Cycle 2). Dexamethasone intravenously (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) and 5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy. Doxorubicin 25 mg/m\^2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m\^2) as part of AI Chemotherapy.

Arm 2, Two Doses: Fosaprepitant 150 mg IV Day 1 + Day 4 of Cycle 1 or Day 1 + Day 4 of Cycle 2. Participants randomized to Group 1 (Fosaprepitant Cycle 1 + No Fosaprepitant Cycle 2); or Group 2 (No Fosaprepitant Cycle 1 and Fosaprepitant Cycle 2). Dexamethasone intravenously (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) and 5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy. Doxorubicin 25 mg/m\^2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m\^2) as part of AI Chemotherapy.

150 mg administered intravenously, delivered in either single dose or two doses, on Day 1 for single dose and on Days 1 and 4 for two doses, varying between Cycle 1 or Cycle 2 depending upon randomization to arm.

Intravenous push (IVPB) daily for 5 days (12 mg on day 1, and 8 mg on days 2-5)

5HT3 receptor antagonist as standard of care 30 minutes prior to chemotherapy

5HT3 receptor antagonist

Doxorubicin + Mesna + + Ifosfamide + Vincristine, chemotherapy cycles repeated every 3-4 weeks for up to 6 cycles. Chemotherapy drugs listed separately, individual dosages, etc.

Ifosfamide-based chemotherapy (AI)

25 mg/m\^2/day IV continuous infusion for 72 hours on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m\^2) as part of AI Chemotherapy.

Prior to ifosfamide (Day 1) - 500 mg/m\^2 (20% of ifosfamide dose) given simultaneously with ifosfamide and then daily continuous infusion (Days 1-4 completing infusion on day 4) - 1,500 mg/m\^2/day (60% of daily ifosfamide dose) for a total of 6 gm/m\^2. The mesna infusion complete 24 hours after last dose of ifosfamide.

2.5 g/m\^2 IV bolus over 3 hours on days 1, 2, 3, 4 (total dose: 10 g/m\^2).

2 mg IV by rapid infusion (Day 1) may be given to participants with sarcomas of small cell histology.

Saroj Vadhan-Raj, MD

The goal of this clinical research study is to learn how different doses of fosaprepitant may effect how ifosfamide-based chemotherapy is absorbed by the body. Researchers also want to learn if fosaprepitant can help to control or prevent delayed nausea and/or vomiting that may be caused by chemotherapy. The safety of this drug will also be studied.

Fosaprepitant is designed to block the natural substance in the brain that causes nausea and vomiting. This may help to prevent and/or control nausea and vomiting caused by chemotherapy.

Study Groups:

If you are found to be eligible to take part in this study, you will receive fosaprepitant during 21-day chemotherapy cycles. You will be randomly assigned (as in a toss of dice) to 1 of 2 study groups, each with 2 divisions:

* If you are in Group A1, you will receive fosaprepitant on Day 1 of Cycle 1.
* If you are in Group A2, you will receive fosaprepitant on Day 1 of Cycle 2.
* If you are in Group B1, you will receive fosaprepitant on Days 1 and 4 of Cycle 1.
* If you are in Group B2, you will receive fosaprepitant on Days 1 and 4 Cycle 2.

You and the study staff will know to which group and division you are assigned. Each time you receive the drug, you will receive it by vein over about 20-30 minutes.

You will also receive the ifosfamide-based chemotherapy prescribed by your doctor, as well as standard drugs for preventing nausea and vomiting (such as ondansetron, lorazepam, diphenhydramine, and promethazine). You will sign a separate consent form that will describe these treatments in detail, along with their risks.

You will receive dexamethasone before chemotherapy, every day for 5 days, to help prevent nausea and vomiting.

Before each chemotherapy cycle, you will be given a study diary. Each day, you will record any side effects you may . You should bring your study diary to every study visit so the study staff can review it.

Study Visits:

Before each cycle that you receive fosaprepitant, the following tests and procedures will be performed:

* You will have a physical exam.
* Your vital signs, weight, and performance status will be recorded.
* You will fill out the same questionnaire you did at screening.
* You will be asked about any other drugs you may be taking. Be sure to tell the study doctor about all drugs (including vitamins, herbal products, and nutritional supplements), because some drugs/substances will cause side effects when taken at the same time as fosaprepitant.
* Blood (about 5 teaspoons) will be drawn for routine tests.

Blood (about 1 teaspoon) will also be drawn 2 times each week during Cycles 1 and 2 for routine tests.

Pharmacokinetic Testing:

On Days 1 and 4 of Cycles 1 and 2 of chemotherapy, blood samples (about 2 teaspoons each time) will be drawn for pharmacokinetic (PK) testing, when possible. PK testing measures the amount of study drug in the body at different time points. The blood will be drawn before you receive ifosfamide, at the end of the infusion, and 4 more times in the 24 hours after the infusion.

Length of Study:

You may receive up to 6 cycles of chemotherapy (and up to 5 cycles of fosaprepitant). You will no longer be able to take the study drug if the disease gets worse or if intolerable side effects occur.

Your participation on the study will be over once you have completed the end-of-study visit.

End-of-Study Visit:

About 3 weeks after your last dose of fosaprepitant, you will return for an end-of-study visit. At this visit, the following tests and procedures will be performed:

* You will have a physical exam.
* Your vital signs, weight, and performance status will be recorded.
* You will fill out the same questionnaire you did at screening.
* You will be asked about any other drugs you may be taking.
* Blood (about 5 teaspoons) will be drawn for routine tests.

This is an investigational study. Fosaprepitant is FDA approved and commercially available in combination with other drugs for the prevention of nausea and vomiting that may be caused by chemotherapy. It is investigational to study how fosaprepitant may affect the drug levels of ifosfamide in the blood and how many doses should be given.

Up to 36 patients will take part in this study. All will be enrolled at MD Anderson.

Fosaprepitant in Patients Receiving Ifosfamide-based Regimen

Evaluation of Fosaprepitant's Effect on Drug Metabolism in Sarcoma Patients Receiving Ifosfamide-based Multi-day Chemotherapy Regimen

Complete response (CR) defined as: No emetic episodes and no rescue medications. This is a cross-over designed study, the outcomes by single dose, two doses and control cycles were evaluated by combining the results from both cycle 1 and cycle 2 according to the treatment received.

Merck Sharp & Dohme LLC

M.D. Anderson Cancer Center

Number of participants for different study groups are: 22 single dose, Arm A (11 from group 1, cycle 1 \& 11 from group 2, cycle 2); 17 two doses, Arm B (9 from group 1, cycle 1 \& 8 from group 2, cycle 2); 37 control cycle \[Arm A: 21(12 from group 1, cycle 2 \& 11 from group 2,cycle 1); Arm B: 16(8 from group 1, cycle 2 \& 8 from group 2,cycle 1)\].

Control Cycle (Arm A/Arm B)

Fosaprepitant 150 mg intravenous (IV) Day 1 of Cycle 1 (Group 1) or Day 1 of Cycle 2 (Group 2). Participants Randomized to Group 1 (Fosaprepitant Cycle 1 + No Fosaprepitant Cycle 2) or Group 2 (No Fosaprepitant Cycle 1 + Fosaprepitant Cycle 2).

Arm A: Single Dose, Day 1

Fosaprepitant 150 mg IV Day 1 + Day 4 of Cycle 1 (Group 1) or Day 1 + Day 4 of Cycle 2 (Group 2). Participants Randomized to Group 1 (Fosaprepitant Cycle 1 + No Fosaprepitant Cycle 2) or Group 2 (No Fosaprepitant Cycle 1 + Fosaprepitant Cycle 2).

Arm B: Two Doses, Day 1 + Day 4

Total

Between 19 and 65 years

Age, Customized

Sex: Female, Male

United States

Region of Enrollment

Saroj Vadhan-Raj, MD/Professor, Sarcoma Medical Oncology

Out of 40 eligible participants, 2 participants had change of treatment, 1 participant was noncompliant and 1 participant had an adverse event related to chemotherapy. 36 participants completed cycle 1 and cycle 2.

Complete Response

Fosaprepitant 150 mg intravenous (IV) Day 1 of Cycle 1 (Group 1). Participants Randomized to Group 1 (Fosaprepitant Cycle 1 + No Fosaprepitant Cycle 2). Dexamethasone IVPB daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) and 5HT3 receptor antagonist as standard of care 30 min prior to chemotherapy. Doxorubicin 25 mg/m\^2/day IV continuous infusion for 72 hrs on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m\^2). Mesna: Prior to ifosfamide (Day 1) - 500 mg/m\^2 given simultaneously with ifosfamide and then daily CI (Days 1-4 completing infusion on day 4) - 1,500 mg/m\^2/day for a total of 6 gm/m\^2. The mesna infusion will complete 24 hrs after the last dose of ifosfamide. Ifosfamide: 2.5 g/m\^2 IV bolus over 3 hrs on days 1, 2, 3, 4 (total dose: 10 g/m\^2). Vincristine: 2 mg IV by rapid infusion (Day 1) may be given to participants with sarcomas of small cell histology.

Arm A: Single Dose, Group 1

Fosaprepitant 150 mg intravenous (IV) Day 1 of Cycle 2 (Group 2). Participants Randomized to Group 2 (No Fosaprepitant Cycle 1 + Fosaprepitant Cycle 2). Dexamethasone IVPB daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) and 5HT3 receptor antagonist as standard of care 30 min prior to chemotherapy. Doxorubicin 25 mg/m\^2/day IV continuous infusion for 72 hrs on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m\^2). Mesna: Prior to ifosfamide (Day 1) - 500 mg/m\^2 given simultaneously with ifosfamide and then daily CI (Days 1-4 completing infusion on day 4) - 1,500 mg/m\^2/day for a total of 6 gm/m\^2. The mesna infusion will complete 24 hrs after the last dose of ifosfamide. Ifosfamide: 2.5 g/m\^2 IV bolus over 3 hrs on days 1, 2, 3, 4 (total dose: 10 g/m\^2). Vincristine: 2 mg IV by rapid infusion (Day 1) may be given to participants with sarcomas of small cell histology.

Arm A: Single Dose, Group 2

Fosaprepitant 150 mg IV Day 1 + Day 4 of Cycle 1 (Group 1). Participants Randomized to Group 1 (Fosaprepitant Cycle 1 + No Fosaprepitant Cycle 2). Dexamethasone IVPB daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) and 5HT3 receptor antagonist as standard of care 30 min prior to chemotherapy. Doxorubicin 25 mg/m\^2/day IV continuous infusion for 72 hrs on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m\^2). Mesna: Prior to ifosfamide (Day 1) - 500 mg/m\^2 given simultaneously with ifosfamide and then daily CI (Days 1-4 completing infusion on day 4) - 1,500 mg/m\^2/day for a total of 6 gm/m\^2. The mesna infusion will complete 24 hrs after the last dose of ifosfamide. Ifosfamide: 2.5 g/m\^2 IV bolus over 3 hrs on days 1, 2, 3, 4 (total dose: 10 g/m\^2). Vincristine: 2 mg IV by rapid infusion (Day 1) may be given to participants with sarcomas of small cell histology.

Arm B: Two Doses, Group 1

Fosaprepitant 150 mg IV Day 1 + Day 4 of Cycle 2 (Group 2). Participants Randomized to Group 2 (No Fosaprepitant Cycle 1 + Fosaprepitant Cycle 2). Dexamethasone IVPB daily for 5 days (12 mg on day 1, and 8 mg on days 2-5) and 5HT3 receptor antagonist as standard of care 30 min prior to chemotherapy. Doxorubicin 25 mg/m\^2/day IV continuous infusion for 72 hrs on days 1, 2, and 3, completing infusion on day 4 (total dose: 75 mg/m\^2). Mesna: Prior to ifosfamide (Day 1) - 500 mg/m\^2 given simultaneously with ifosfamide and then daily CI (Days 1-4 completing infusion on day 4) - 1,500 mg/m\^2/day for a total of 6 gm/m\^2. The mesna infusion will complete 24 hrs after the last dose of ifosfamide. Ifosfamide: 2.5 g/m\^2 IV bolus over 3 hrs on days 1, 2, 3, 4 (total dose: 10 g/m\^2). Vincristine: 2 mg IV by rapid infusion (Day 1) may be given to participants with sarcomas of small cell histology.

Arm B: Two Doses, Group 2

Cycle 1

Cycle 2

Ear, Nose, and Throat Diseases

Substance Related Disorders

Wounds and Injuries

Head and Neck Neoplasms

Ototoxicity

Ear Diseases

Otorhinolaryngologic Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Micronutrients

Pharmaceutical Solutions

Vitamins

Vitamin A

Retinol palmitate

Hyaluronic Acid

Cisplatin

Sodium thiosulfate

Antidotes

Protective Agents

Antioxidants

Antitubercular Agents

Chelating Agents

Retinol

Trans-tympanic injection of a sodium thiosulfate gel

A sodium thiosulfate hyaluronate gel will be prepared by mixing 0.55 ml of a 25% solution of sodium thiosulfate pentahydrate (Seacalphyx, DIN 02386666, Seaford Pharmaceuticals Inc.) and 0.55 ml of a hyaluronate gel (Healon 10 mg, Abbott Medical Optics Inc.). On the day before each Cisplatin treatment an otologist will deposit 0.1 ml of the gel exactly on the round window of the middle ear.

Francois Meyer, MD, DSc

This study evaluates whether a gel containing sodium thiosulfate deposited via a trans-tympanic injection on the round window of the middle ear could reduce the ototoxicity caused by the drug Cisplatin among patients with head and neck cancer treated by chemoradiation. One ear selected randomly will be treated while the other will serve as control.

Background

Cisplatin (cis-DiammineDichloridoPlatinum, DDP) is an antineoplastic agent used in the treatment of solid malignant tumors in adults and is also a key part of treatment for many children and adolescents with cancer. However, treatment with Cisplatin carries the risk of serious dose-limiting adverse effects. Ototoxicity is of major concern since the associated hearing loss greatly impairs patients' quality of life and no preventive treatment is presently available. Cisplatin ototoxicity is an important problem for patients treated for head and neck squamous cell carcinoma (HNSCC) who receive repeatedly high doses.

Cisplatin causes an accumulation of reactive oxygen species (ROS) in the cochlea, triggering damage to the outer hair cells of the organ of Corti. Sulfur-containing antioxidants can neutralize ROS following Cisplatin intoxication, and thus represent a potential preventive measure. A few sulfur-containing molecules have been studied. Experimental and human studies have shown that sodium thiosulfate (STS) can protect against Cisplatin-induced ototoxicity. However, when administered through the blood stream, STS interfere with Cisplatin treatment efficacy. To counter the ototoxic effects of Cisplatin treatment without impairing its efficacy, a local pharmacology approach directly aiming at the cochlea, would represent a powerful clinical strategy.

The proposed study is the first to test the efficacy of STS administered locally in the middle ear to prevent Cisplatin-induced ototoxicity in humans.

Objective

The objective of this study is to test the efficacy of trans-tympanic injections of a sodium thiosulfate-hyaluronate gel prior to cisplatin treatments to prevent cisplatin-induced ototoxicity in patients with locally advanced head and neck cancer.

The principal objective is to test the efficacy of the trans-tympanic injections of the gel at pure tone high frequencies. Exploratory analyses for secondary objectives will assess 1) cochlear damage, specifically hair cell function and 2) hearing loss at frequencies used for speech perception. Other outcomes considered are the severity of ototoxicity and the adverse effects of the trans-tympanic injections.

Methods

The proposed study is a randomized controlled trial. For each participant, one randomly selected ear will receive the treatment while the other ear will not. For ethical reasons, the control ear will not receive a placebo injection.

Participants to the trial will be recruited at the radiation therapy department of the CHU de Québec. Eligible participants are patients newly diagnosed with a locally advanced squamous cell carcinoma of the head and neck scheduled to be treated with concomitant chemoradiation. This treatment includes Cisplatin 100 mg/m2 on days 1, 22, and 43 after the first radiation fraction.

At the end of the first day of radiation therapy, the pharmacy department of the CHU de Québec will prepare the sodium thiosulfate hyaluronate gel by mixing 0.55 ml of a 25% solution of sodium thiosulfate pentahydrate (Seacalphyx, Drug identification number (DIN) 02386666, Seaford Pharmaceuticals Inc.) and 0.55 ml of a hyaluronate gel (Healon 10 mg, Abbott Medical Optics Inc.). After a local anesthesia of the tympanic membrane, the otologist will deposit 0.1 ml of the gel exactly on the round window of the middle ear. From there the STS should diffuse towards the cochlea. The same procedure will be repeated on the eve of the subsequent Cisplatin treatments on days 22 and 43.

To assess the effect of the trial intervention, a complete audiologic evaluation will be conducted before and one month after the end of chemoradiation therapy. The CHU de Québec audiologists will perform audiograms at frequencies ranging from 0.5 to 14 kHz. Sound intensity will be measured as dBHL(decibel hearing level). Speech reception thresholds will also be assessed. In addition, distortion product otoacoustic emissions (DPOAEs) recording will also be performed. Otoacoustic emissions measurements could detect hair cell damage due to Cisplatin early. The final audiologic evaluation will be conducted by an audiologist blinded to the ear assignment who would not have access to the trial and hospital records.

Adverse effects of the transtympanic injection will be documented according to the Common Terminology Criteria for Adverse Events v4.0 (CTCAE). In addition, to identify unexpected adverse effects of the trial intervention on hearing, a shorter unblinded audiogram will be conducted before proceeding to the second and third transtympanic injections. Data from these audiograms will not be used in the main analysis.The follow-up for audiologic safety monitoring will be continued for one year after the end of the trial.

The principal outcome is the hearing loss defined by the difference between the average permanent threshold shift (PTS) in dB (decibel) at four pure tone high frequencies (9, 10, 12.5 and 14 kHz) using the data from the audiograms done before and after Cisplatin therapy, for each patient and for each ear. The average PTS in dB at these pure tone high frequencies will be compared between the treated and the control ears using a t-test for paired data. A planned interim analysis will be conducted when half of the anticipated participants would have completed the follow-up. In the interim analysis, the test for superiority will be done with two-sided alpha=0.01 and the results shown only to the Data and Safety Monitoring Committee (DSMC). If the DSMC recommendation is to continue the trial as planned, the final analysis will be done with two-sided alpha=0.045 in order to keep the trial overall statistical significance level to 0.05.

Exploratory analyses for secondary outcomes will assess 1) cochlear damage, specifically hair cell function obtained from the results of DPOAEs, ands 2) the difference between the PTS in dB at pure tone averages (0.5 to 8 kHz), which represent frequencies for speech perception. Other outcomes considered are ototoxicity severity according to CTCAE, and adverse effects of the transtympanic injections.

The investigators have established an independent DSMC to overview the conduct of the trial comprising experts in biostatistics, audiology, and haemato-oncology.

Efficacy of Trans-tympanic Injections of a Sodium Thiosulfate Gel to Prevent Cisplatin-induced Ototoxicity

Randomized Controlled Trial to Test the Efficacy of Trans-tympanic Injections of a Sodium Thiosulfate Gel to Prevent Cisplatin-induced Ototoxicity in Patients With Head and Neck Cancer

Hearing loss defined by the difference between the average permanent threshold shift (PTS) in dB (decibel) at four pure tone high frequencies (9, 10, 12.5 and 14 kHz) using the data from the audiograms done before and one month after Cisplatin therapy, for each patient and for each ear.

Cochlear damage defined by the difference between the distortion product otoacoustic emissions (DPOAEs) recording before and one month after Cisplatin therapy, for each patient and for each ear.

Hearing loss defined by the difference between the average permanent threshold shift (PTS) in dB (decibel) at four pure tone frequencies (0.5 to 8 kHz) using the data from the audiograms done before and one month and one year after Cisplatin therapy, for each patient and for each ear.

Ototoxicity severity according to CTCAE after each trans-tympanic injection

CHU de Quebec-Universite Laval

Researcher

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Recurrence

Uterine Cervical Neoplasms

Neoplasms, Glandular and Epithelial

Disease Attributes

Antibodies

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Immunoglobulins

Immunologic Factors

Eligible patients according to inclusion and exclusion criteria.

Patients will receive Donafenib (200mg, bid) combined with paclitaxel (135mg/m2) and cisplatin (creatinine clearance rate \> 60ml/min, 50 mg/m2) or paclitaxel (175 mg/m2) and carboplatin AUC=5 (40ml/min \< creatinine clearance rate \< 60ml/min) ± PD-1 antibody every 3 weeks.

Donafenib combined with paclitaxel and platinum ± PD-1 antibody

Lei Li, M.D.

This study is to evaluate the safety and tolerability of Donafenib combined with paclitaxel and platinum ± programmed death 1 monoclonal antibody (PD-1 antibody) in patients with recurrent cervical cancer.

This is a single center, non-randomized, open-label Phase II clinical study to investigate the efficacy and tolerability of Donafenib combined with paclitaxel and platinum ± PD-1 antibody in patients with recurrent cervical cancer. In total 20 patients will receive Donafenib (200mg, bid) combined with paclitaxel (135mg/m2) and cisplatin (creatinine clearance rate \> 60ml/min, 50 mg/m2) or paclitaxel (175 mg/m2) and carboplatin AUC=5 (40ml/min \< creatinine clearance rate \< 60ml/min) ± PD-1 antibody every 3 weeks.

Actual Study Start Date: March 27, 2022 Estimated Primary Completion Date: December 27, 2023 Estimated Study Completion Date: June 27, 2024

Arms There is only one arm, i.e., group of Donafenib combined with paclitaxel and platinum ± PD-1 antibody. Each treatment period was 21 days. Patients will be treated with 4-6 cycles of Donafenib plus TP or TC ± PD-1 antibody. After completion of the combination, patients will be maintained on Donafenib until disease progression or unacceptable toxicity occurs (up to 12 months)

Donafenib was taken orally at 200 mg twice on an empty stomach (1 hour before or \> 2 hours after meal) in the morning and evening of each administration day, with an interval of about 12 hours. Maintain the same dose until disease progression, death, toxicity intolerance, withdrawal of informed consent, initiation of new antineoplastic therapy, or termination of treatment for other reasons specified in the protocol, for a maximum of 12 months.

Paclitaxel and platinum:

If creatinine clearance rate \> 60ml/min: on Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of paclitaxel 135 mg/m2plus cisplatin 50 mg/m2.

If 40ml/min \< creatinine clearance rate \< 60ml/min:on Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of paclitaxel 175 mg/m2 plus carboplatin AUC=5.

PD-1 antibody: PD-1 antibody is not mandatory, intravenous infusion on the first day of each cycle, every 3 weeks for a cycle until disease progression, death, toxicity intolerance, withdrawal of informed consent, initiation of new antitumor therapy, or termination of treatment for other reasons specified in the protocol, the longest treatment period is 12 months.

The primary outcome measure is progression-free survival. The secondary outcome measures include overall survival, objective response rate, etc.

Donafenib for Recurrent Cervical Cancer

Efficacy and Safety of Donafenib Combined With Paclitaxel and Platinum in Patients With Recurrent, Metastatic, and Persistent Advanced Cervical Cancer: A Single-arm, Phase II Study

PFS defined as the time the duration from date of enrollment to the first documented disease progression, or death due to any cause, whichever occurs first.

Overall survival is defined as the duration from date of enrollment to the date of death from any cause.

ORR is defined as the percentage of participants in the analysis population who have a complete or partial remission.

DCR is defined as the percentage of participants in the analysis population who have a complete or partial remission, or stable disease (SD).

Adverse event (AE)、Treatment emergent adverse event (TEAE)、Serious adverse event (SAE).

Lei Li

Professor

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

65 patients will receive the immediate treatment with focal HIFU in order to destroy the cancer without causing side effects. HIFU treatment will be conducted with the Focal One® device. The treatment area will be defined using MRI data and 3D biopsies. A safety distance of at least 9 mm will be defined around the tumor. An intraoperative contrast echocardiographic control will be performed to evaluate the necrotic area. If necessary, additional HIFU lesions will be performed during the same session. In case of residual tumor demonstrated during control biopsies, additional treatment of this tumor with focal HIFU may be proposed.

Patients randomized in this arm will also have PSA dosage, MRI exam, questionnaires and prostatic biopsies during their follow up.

65 patients will be randomized to active surveillance and will have exactly the same follow-up as treated patients excepting the HIFU treatment.

Active surveillance is a therapeutic option that shifts the eventual moment of curative treatment while remaining within a window of curability of the disease.

Patients randomized in this arm will also have PSA dosage, MRI exam, questionnaires and prostatic biopsies during their follow up.

HIFU treatment will be conducted with the Focal One® device. The treatment area will be defined using MRI data and 3D biopsies. A safety distance of at least 9 mm will be defined around the tumor. An intraoperative contrast echocardiographic control will be performed to evaluate the necrotic area. If necessary, additional HIFU lesions will be performed during the same session. In case of residual tumor demonstrated during control biopsies, additional treatment of this tumor with focal HIFU may be proposed.

treatment with focal HIFU

PSA dosage will be regularly performed during patient follow up thanks to blood sampling.

PSA dosage

MRI exam will be regularly performed during patient follow up.

Patients will have to complete five questionnaires during their follow up : QLQ-C30 (Quality of Life questionnaire), EPIC-26 (The Expanded Prostate Cancer Index Composite), IPSS (International Prostate Score Symptom), IIEF-5 (The International Index of Erectile Function), STAI-YB (State-Trait Anxiety Inventory)

Questionnaires

Prostatic biopsies will be regularly performed during patient follow up.

Prostatic biopsies

The percentage of malignant prostate tumors detected very early is constantly increasing and the number of well differentiated tumors, with small volume and low risk of progression increases. When a tumor of this type is identified, radical prostatectomy remains the reference treatment, but this treatment is not without side effects. Active surveillance is a strategy which aims at detecting an early development of the cancerous disease in order to propose curative treatment in a timely manner and thus improve specific survival. Patients are therefore re-evaluated each year by rectal examination, PSA (Prostate-Specific Antigen) assay. Active surveillance remains difficult to manage psychologically for both the patient and the practitioner, because of the lack of treatment on the one hand and a rate of non-curable cancers close to 50% when signs of progression trigger a radical treatment.

The aim of the focal treatment HIFU (High Intensity Focused Ultrasound) is to destroy the cancer without causing side effects in contrast to radical treatments. It is in this sense that it is positioned both as an alternative to radical surgery and as an alternative to active surveillance.

Phase 3, Multicenter, Randomized Study, Evaluating the Efficacy and Tolerability of Focused HIFU (High Intensity Focused Ultrasound) Therapy Compared to Active Surveillance in Patients With Significant Low Risk Prostate Cancer

Phase 3, Multicenter, Randomized Study, Evaluating the Efficacy and Tolerability of Focused HIFU Therapy Compared to Active Surveillance in Patients With Significant Low Risk Prostate Cancer

The primary endpoint is the comparison between the 2 groups of the proportion of patient converting to a radical treatment at 48 months of follow-up. Conversion to a radical treatment is define as a medical decision based on the following criteria:

* An increase in Gleason score to a score 7 (3 + 4) with bilateral involvement (Gleason 6 or 7).
* An increase in the Gleason score to a score 7 (3 + 4) with tumor whose location is not compatible with a focal treatment (impossibility to apply safety margins of 9mm).
* An increase in Gleason score to a score of 7 (4 + 3) or higher.
* Risk of lymph node invasion\> 5% (calculated with the MSKCC nomogram)
* An extension of the tumor beyond the prostatic capsule (MRI and / or biopsies).
* Appearance of pelvic ganglion metastases.

The objective is to compare between the 2 groups the proportion of patients needing additional treatment (focal or radical) at 24 months. This includes patients who wish or require radical treatment (prostatectomy, radiotherapy), total focal treatment, focal treatment for patients in the active surveillance group or additional treatment for patients in the treatment group.

The objective is to compare between the 2 groups the proportion of patients needing additional treatment (focal or radical) at 48 months. This includes patients who wish or require radical treatment (prostatectomy, radiotherapy), total focal treatment, focal treatment for patients in the active surveillance group or additional treatment for patients in the treatment group.

The rate of positive biopsies in the untreated lobe and treated lobe evaluated and will be used to evaluate the oncological evolution at 24 months.

The rate of positive biopsies in the untreated lobe and treated lobe will be measured and will be used to evaluate the oncological evolution at 48 months.

The clinically significant cancer rate (Gleason 7 or invasion of more than 3 biopsies or invasion\> 3 mm regardless of Gleason) in the untreated lobe and the treated lobe will be measured and will be used to evaluate the oncological evolution at 24 months.

The clinically significant cancer rate (Gleason 7 or invasion of more than 3 biopsies or invasion\> 3 mm regardless of Gleason) in the untreated lobe and the treated lobe will be measured and will be used to evaluate the oncological evolution at 48 months.

Evolution of the Gleason score (appearance of Gleason ≥7) will be measured and will be used to evaluate the oncological evolution at 24 months.

Evolution of the Gleason score (appearance of Gleason ≥7) will be measured and will be used to evaluate the oncological evolution at 48 months.

Appearance of another cancerous focus in the other half of the prostate will be supervised and will be used to evaluate the oncological evolution at 24 months.

Appearance of another cancerous focus in the other half of the prostate will be supervised and will be used to evaluate the oncological evolution at 48 months.

Appearance of metastases (lymph node or bone) will be supervised and will be used to evaluate the oncological evolution at 24 months.

Appearance of metastases (lymph node or bone) will be supervised and will be used to evaluate the oncological evolution at 48 months.

Appearance of an extra capsular extension will be supervised and will be used to evaluate the oncological evolution at 24 months.

Appearance of an extra capsular extension will be supervised and will be used to evaluate the oncological evolution at 48 months.

Overall survival at 48 months will be measured from the date of inclusion to the date of death, all causes of death combined or the date of last new or point date to 48 months.

Prostate cancer specific survival at 48 months will be measured from the date of inclusion to the date of death related to prostate cancer or the date of last new or point date to 48 months

Prostate cancer specific survival at 48 months will be measured from the date of inclusion to the date of first metastasis , or the date of last new or point date to 48 months

comparison between the 2 groups of the proportion of serious adverse effect at 48 months

quality of life will be compared between the two groups and assessed using the QLQC30 questionnaire

urinary function will be compared between the two groups and assessed using the EPIC-26 questionnaire.

urinary function will be compared between the two groups and assessed using the IPSS questionnaire.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fosaprepitant in Patients Receiving Ifosfamide-based Regimen	NCT01490060	Sarcoma Chemotherapy-in... Effects of Chem... Adverse Effects...	Fosaprepitant Dexamethasone 5HT3 receptor a... Ifosfamide-base... Doxorubicin Mesna Ifosfamide Vincristine	18 Years - 65 Years	M.D. Anderson Cancer Center
Efficacy of Trans-tympanic Injections of a Sodium Thiosulfate Gel to Prevent Cisplatin-induced Ototoxicity	NCT02281006	DDP Head and Neck C... Adverse Effect	Trans-tympanic ...	18 Years -	CHU de Quebec-Universite Laval
Donafenib for Recurrent Cervical Cancer	NCT05310331	Targeted Therap... Chemotherapy Recurrent Cervi... Metastatic Cerv... Persistent Adva... Survival Outcom... Adverse Effect	Donafenib combi...	18 Years - 75 Years	Peking Union Medical College Hospital
Phase 3, Multicenter, Randomized Study, Evaluating the Efficacy and Tolerability of Focused HIFU (High Intensity Focused Ultrasound) Therapy Compared to Active Surveillance in Patients With Significant Low Risk Prostate Cancer	NCT03531099	Prostate Cancer	treatment with ... PSA dosage MRI Questionnaires Prostatic biops...	50 Years - 80 Years	Hospices Civils de Lyon
PD-1 Antibody Combined With Chemoradiotherapy in Recurrent Nasopharyngeal Carcinoma Patients	NCT03907826	Recurrent Nasop...	PD-1 blocking a... GP IMRT	18 Years - 70 Years	Sun Yat-sen University
The Effect of Peppermint Oil on Nausea, Vomiting and Retching in Cancer Patients Undergoing Chemotherapy	NCT04118322	Chemotherapy Ef... Adverse Effect Nursing Caries	aromatherapy (p...	18 Years -	TC Erciyes University
The Effect of Peppermint Oil on Nausea, Vomiting and Retching in Cancer Patients Undergoing Chemotherapy	NCT04118322	Chemotherapy Ef... Adverse Effect Nursing Caries	aromatherapy (p...	18 Years -	TC Erciyes University
Efficacy Evaluation of Focused HIFU (High Intensity Focused Ultrasound) Therapy in Patients With Localized Intermediate Risk Prostate Cancer	NCT03568188	Prostate Cancer	treatment with ... PSA dosage MRI Questionnaires Prostatic biops... blood test urine test	50 Years - 80 Years	Hospices Civils de Lyon
Efficacy of Trans-tympanic Injections of a Sodium Thiosulfate Gel to Prevent Cisplatin-induced Ototoxicity	NCT02281006	DDP Head and Neck C... Adverse Effect	Trans-tympanic ...	18 Years -	CHU de Quebec-Universite Laval

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